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Placebo

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   For other uses, see Placebo (disambiguation) and Placebo effect
   (disambiguation).
   "Sugar pill" redirects here. For Kids of 88 album, see Sugarpills.
   The placebo effect can be produced by inert tablets, by sham surgery,
   and by false information, such as when electrical stimulation is turned
   "off" in those with Parkinson's disease implanted brain electrodes.^[1]

   A placebo (/pləˈsiboʊ/ plə-SEE-boh; Latin placēbō, "I shall please"^[2]
   from placeō, "I please") is a simulated or otherwise medically
   ineffectual treatment for a disease or other medical condition intended
   to deceive the recipient. Sometimes patients given a placebo treatment
   will have a perceived or actual improvement in a medical condition, a
   phenomenon commonly called the placebo effect.

   In medical research, placebos are given as control treatments and
   depend on the use of measured deception. Common placebos include inert
   tablets, vehicle infusions, sham surgery,^[3] and other procedures
   based on false information.^[1] However, placebos can also have a
   surprisingly positive effect on a patient who knows that the given
   treatment is without any active drug, as compared with a control group
   who knowingly did not get a placebo.^[4]

   In one common placebo procedure, however, a patient is given an inert
   pill, told that it may improve his/her condition, but not told that it
   is in fact inert. Such an intervention may cause the patient to believe
   the treatment will change his/her condition; and this belief may
   produce a subjective perception of a therapeutic effect, causing the
   patient to feel their condition has improved — or an actual improvement
   in their condition. This phenomenon is known as the placebo effect.

   Placebos are widely used in medical research and medicine,^[5] and the
   placebo effect is a pervasive phenomenon;^[5] in fact, it is part of
   the response to any active medical intervention.^[6] Archie Cochrane
   suggested in 1972^[7] "It is important to distinguish the very
   respectable, conscious use of placebos. The effect of placebos has been
   shown by randomized controlled trials to be very large. Their use in
   the correct place is to be encouraged […]"

   The placebo effect points to the importance of perception and the
   brain's role in physical health. However, the use of placebos as
   treatment in clinical medicine (as opposed to laboratory research) is
   ethically problematic as it introduces deception and dishonesty into
   the doctor-patient relationship.^[8] The United Kingdom Parliamentary
   Committee on Science and Technology has stated that: "...prescribing
   placebos... usually relies on some degree of patient deception" and
   "prescribing pure placebos is bad medicine. Their effect is unreliable
   and unpredictable and cannot form the sole basis of any treatment on
   the NHS."^[3]

   Since the publication of Henry K. Beecher's The Powerful Placebo ^[9]
   in 1955, the phenomenon has been considered to have clinically
   important effects.^[10] This view was notably challenged when, in 2001,
   a systematic review of clinical trials concluded that there was no
   evidence of clinically important effects, except perhaps in the
   treatment of pain and continuous subjective outcomes.^[10] The article
   received a flurry of criticism,^[11] but the authors later published a
   Cochrane review with similar conclusions (updated as of
   2010^[update]).^[12] Most studies have attributed the difference from
   baseline until the end of the trial to a placebo effect, but the
   reviewers examined studies which had both placebo and untreated groups
   in order to distinguish the placebo effect from the natural progression
   of the disease.^[10] However these conclusions have been criticized
   because of the great variety of diseases—more than 40—in this
   metastudy. The effect of placebo is very different in different
   diseases. By pooling quite different diseases the results can be
   leveled out.

Contents

     * 1 Definitions, effects, and ethics
     * 2 History
     * 3 Mechanism of the effect
          + 3.1 Expectancy and conditioning
          + 3.2 Placebo effect and the brain
          + 3.3 Brain and body
          + 3.4 Evolved health regulation
     * 4 Clinical utility
          + 4.1 Duration
          + 4.2 Clinical significance
          + 4.3 Negative effects
          + 4.4 Doctor-patient relationship
     * 5 The individual
          + 5.1 Who is affected
          + 5.2 Individual differences
          + 5.3 Genes
     * 6 Symptoms and conditions
          + 6.1 Pain
          + 6.2 Depression
          + 6.3 Gastric and duodenal ulcers
          + 6.4 Chronic fatigue syndrome
          + 6.5 List of medical conditions
     * 7 Effects on research
          + 7.1 Placebo-controlled studies
          + 7.2 Nocebo
          + 7.3 Placebo ingredients
     * 8 See also
     * 9 References
     * 10 External links

Definitions, effects, and ethics[edit]

   See also: Medical ethics

   A placebo has been defined as "a substance or procedure… that is
   objectively without specific activity for the condition being
   treated".^[11] Under this definition, a wide variety of things can be
   placebos and exhibit a placebo effect. Pharmacological substances
   administered through any means can act as placebos, including pills,
   creams, inhalants, and injections. Medical devices such as ultrasound
   can act as placebos.^[13]^[14] Sham surgery,^[15]^[16]^[17] sham
   electrodes implanted in the brain,^[1] and sham acupuncture, either
   with sham needles or on fake acupuncture points, have all exhibited
   placebo effects.^[18] Bedding not treated to reduce allergies has been
   used as a placebo to control for treated bedding.^[19] The physician
   has even been called a placebo;^[20] a study found that patient
   recovery can be increased by words that suggest the patient "would be
   better in a few days", and if the patient is given treatment, that "the
   treatment would certainly make him better" rather than negative words
   such as "I am not sure that the treatment I am going to give you will
   have an effect".^[21] The placebo effect may be a component of
   pharmacological therapies: Pain killing and anxiety reducing drugs that
   are infused secretly without an individual's knowledge are less
   effective than when a patient knows they are receiving them. Likewise,
   the effects of stimulation from implanted electrodes in the brains of
   those with advanced Parkinson's disease are greater when they are aware
   they are receiving this stimulation.^[22] Sometimes administering or
   prescribing a placebo merges into fake medicine.

   The placebo effect has sometimes been defined as a physiological effect
   caused by the placebo, but Moerman and Jonas have pointed out that this
   seems illogical, as a placebo is an inert substance that does not
   directly cause anything. Instead they introduced the term "meaning
   response" for the meaning that the brain associates with the placebo,
   which causes a physiological placebo effect. They propose that the
   placebo, which may be unethical, could be avoided entirely if doctors
   comfort and encourage their patients' health.^[11] Ernst and Resch also
   attempted to distinguish between the "true" and "perceived" placebo
   effect, as they argued that some of the effects attributed to the
   placebo effect could be due to other factors.^[23]

   The placebo effect has been controversial throughout history. Notable
   medical organizations have endorsed it,^[24] but in 1903 Richard Cabot
   concluded that it should be avoided because it is deceptive. Newman
   points out the "placebo paradox", – it may be unethical to use a
   placebo, but also unethical "not to use something that heals". He
   suggests to solve this dilemma by appropriating the meaning response in
   medicine, that is make use of the placebo effect, as long as the "one
   administering… is honest, open, and believes in its potential healing
   power".^[8] Another possible resolution of the ethical dilemma might
   come from the "honest placebo" effect found in a 2010 study^[4] carried
   out by researchers in the Program in Placebo Studies at the Harvard
   Medical School, where patients with irritable bowel syndrome
   experienced a significant beneficial effect even though they were told
   the pills they were taking were placebos, as compared to a control
   group who received no pills.

   Although the placebo effect and theories on its underlying mechanisms
   are mostly understood in terms of human psychology, studies have also
   indicated that non-human animals such as dogs can also have symptoms
   reduced by placebo treatments.^[25]

History[edit]

   Main article: Placebo in history

   The word 'placebo', Latin for "I will please", dates back to a Latin
   translation of the Bible by St Jerome.^[26] It was first used in a
   medicinal context in the 18th century. In 1785 it was defined as a
   "commonplace method or medicine" and in 1811 it was defined as "any
   medicine adapted more to please than to benefit the patient", sometimes
   with a derogatory implication^[27] but not with the implication of no
   effect.^[28] Placebos were widespread in medicine until the 20th
   century, and they were sometimes endorsed as necessary deceptions.^[24]
   In 1903 Richard Cabot said that he was brought up to use placebos,^[24]
   but he ultimately concluded by saying that "I have not yet found any
   case in which a lie does not do more harm than good".^[8] In 1961 Henry
   K. Beecher found^[29] that surgeons he categorized as enthusiasts
   relieved their patients' chest pain and heart problems more than
   skeptic surgeons.^[8] In 1961 Walter Kennedy introduced the word
   nocebo.^[24] Beginning in the 1960s, the placebo effect became widely
   recognized and placebo controlled trials became the norm in the
   approval of new medications.^[30] Later, researchers became interested
   in understanding the placebo effect, rather than just controlling for
   its effects, and in 2011, a Program in Placebo Studies was established
   at the Harvard Medical School.

Mechanism of the effect[edit]

   The placebo effect is highly variable in its magnitude and reliability
   and is typically strongest in measures of subjective symptoms (e.g.,
   pain) and typically weak-to-nonexistent in objective measures of health
   points (e.g., blood pressure, infection clearance).^[citation needed]

   A 2001 meta-analysis of clinical trials with placebo groups and
   no-treatment groups found no evidence for a placebo effect on
   objectively measured outcomes and possible small benefits in studies
   with continuous subjective outcomes (particularly pain).^[10] A 2004
   follow-up analysis found similar results and increased evidence of bias
   in smaller trials that calls into question the apparent placebo effect
   on subjective outcomes.^[31]

   Because the placebo response is simply the patient response that cannot
   be attributed to an investigational intervention, there are multiple
   possible components of a measured placebo effect. These components
   having varying relevance depending on study design and the types of
   observations.^[32] While there is some evidence that placebo
   interventions can alter levels of hormones^[33] or endogenous
   opioids,^[34] other prominent components include expectancy effects,
   regression to the mean,^[35]^[36] and flawed research methodologies.

Expectancy and conditioning[edit]

   The placebo effect is related to the perceptions and expectations of
   the patient; if the substance is viewed as helpful, it can heal, but,
   if it is viewed as harmful, it can cause negative effects, which is
   known as the nocebo effect. In 1985, Irving Kirsch hypothesized that
   placebo effects are produced by the self-fulfilling effects of response
   expectancies, in which the belief that one will feel different leads a
   person to actually feel different.^[37] According to this theory, the
   belief that one has received an active treatment can produce the
   subjective changes thought to be produced by the real treatment.
   Placebos can act similarly through classical conditioning, wherein a
   placebo and an actual stimulus are used simultaneously until the
   placebo is associated with the effect from the actual stimulus.^[38]
   Both conditioning and expectations play a role in placebo effect,^[39]
   and make different kinds of contribution. Conditioning has a
   longer-lasting effect,^[40] and can affect earlier stages of
   information processing.^[41] The expectancy effect can be enhanced
   through factors such as the enthusiasm of the doctor, differences in
   size and color of placebo pills, or the use of other interventions such
   as injections. In one study, the response to a placebo increased from
   44% to 62% when the doctor treated them with "warmth, attention, and
   confidence."^[42] Expectancy effects have been found to occur with a
   range of substances. Those that think that a treatment will work
   display a stronger placebo effect than those that do not, as evidenced
   by a study of acupuncture.^[43]^[44]

   Because the placebo effect is based upon expectations and conditioning,
   the effect disappears if the patient is told that their expectations
   are unrealistic, or that the placebo intervention is ineffective. A
   conditioned pain reduction can be totally removed when its existence is
   explained.^[45] It has also been reported of subjects given placebos in
   a trial of anti-depressants, that "Once the trial was over and the
   patients who had been given placebos were told as much, they quickly
   deteriorated."^[46]

   A placebo described as a muscle relaxant will cause muscle relaxation
   and, if described as the opposite, muscle tension.^[47] A placebo
   presented as a stimulant will have this effect on heart rhythm, and
   blood pressure, but, when administered as a depressant, the opposite
   effect.^[48] The perceived consumption of caffeine has been reported to
   cause similar effects even when decaffeinated coffee is
   consumed,^[49]^[50] although a 2003 study found only limited support
   for this.^[51] Placebos represented as alcohol can cause
   intoxication^[52] and sensorimotor impairment.^[53] Perceived ergogenic
   aids can increase endurance,^[54] speed^[55] and weight-lifting
   ability,^[56] leading to the question of whether placebos should be
   allowed in sport competition.^[57] Placebos can help smokers quit.^[58]
   Perceived allergens that are not truly allergenic can cause
   allergies.^[59] Interventions such as psychotherapy can have placebo
   effects.^[60]^pp 164–173 The effect has been observed in the
   transplantation of human embryonic neurons into the brains of those
   with advanced Parkinson's disease.^[61]

   Because placebos are dependent upon perception and expectation, various
   factors that change the perception can increase the magnitude of the
   placebo response. For example, studies have found that the color and
   size of the placebo pill makes a difference, with "hot-colored" pills
   working better as stimulants while "cool-colored" pills work better as
   depressants. Capsules rather than tablets seem to be more effective,
   and size can make a difference.^[62] One researcher has found that big
   pills increase the effect^[63] while another has argued that the effect
   is dependent upon cultural background.^[64] More pills,^[65]
   branding,^[66] past experience,^[67] and high price^[68] increase the
   effect of placebo pills. Injection^[69] and acupuncture^[18] have
   larger effect than pills. Proper adherence to placebos is associated
   with decreased mortality.^[70]

   Motivation may contribute to the placebo effect. The active goals of an
   individual changes his/her somatic experience by altering the detection
   and interpretation of expectation-congruent symptoms, and by changing
   the behavioral strategies a person pursues.^[71]^[72] Motivation may
   link to the meaning through which people experience illness and
   treatment. Such meaning is derived from the culture in which they live
   and which informs them about the nature of illness and how it responds
   to treatment. Research into the placebo treatment of gastric and
   duodenal ulcers shows that this varies widely with society.^[11] The
   placebo effect in treating gastric ulcers is low in Brazil, higher in
   northern Europe (Denmark, Netherlands), and extremely high in Germany.
   However, the placebo effect in treating hypertension is lower in
   Germany than elsewhere.^[73] Social observation can induce a placebo
   effect such when a person sees another having reduced pain following
   what they believe is a pain reducing procedure.^[74]

   The placebo effect can work selectively, under the influence of various
   psychological factors. If a placebo cream is applied on one hand with
   the expectation that it is an analgesic, it will reduce pain only in
   that hand and not elsewhere on the body.^[75] If a person is given a
   placebo under one name, and they respond, they will respond in the same
   way on a later occasion to that placebo under that name but not if
   under another.^[76]

Placebo effect and the brain[edit]

   Functional imaging upon placebo analgesia shows that it links to the
   activation, and increased functional correlation between this
   activation, in the anterior cingulate, prefrontal, orbitofrontal and
   insular cortices, nucleus accumbens, amygdala, the brainstem
   periaqueductal gray matter,^[77]^[78]^[79] and the spinal
   cord.^[80]^[81]^[82]^[83]

   These changes can act upon the brain's early stages of information
   processing: Research using evoked brain potentials upon painful laser
   pulses, for example, finds placebo effects upon the N2–P2, a biphasic
   negative–positive complex response, the N2 peak of which is at about
   230 ms, and the P2 one at about 380 ms.^[41] They occur not only during
   placebo analgesia but after receiving the analgesic placebo (the areas
   are different here, and involve the medial prefrontal cortex, posterior
   parietal cortex and inferior parietal lobule).^[84]

   Different areas in the higher brain have different functions. The
   prefrontal involvement could be related to recalling the placebo and
   maintaining its cognitive presence in a "self-reinforcing feedback
   loop" (during pain an individual recalls having taken the placebo and
   reduced pain reinforces its status as an analgesic).^[85] The rostral
   anterior cingulate cortex (rACC) and its subcortical connectivity could
   be related to the expectation of potential pain stimuli^[86]^[87]

   The higher brain works by regulating subcortical processes. High
   placebo responses link with enhanced dopamine and mu-opioid activity in
   the circuitry for reward responses and motivated behavior of the
   nucleus accumbens, and, on the converse, anti-analgesic nocebos
   responses were associated with deactivation in this part of the brain
   of dopamine and opioid release.^[78] (It has been known that placebo
   analgesia depends upon the release in the brain of endogenous opioids
   since 1978.^[88]) Such analgesic placebos activation changes processing
   lower down in the brain by enhancing the descending inhibition through
   the periaqueductal gray^[78] on spinal nociceptive reflexes, while the
   expectations of anti-analgesic nocebos acts in the opposite way to
   block this.^[80]

   The brain is also involved in less-studied ways upon nonanalgesic
   placebo effects:
     * Parkinson's disease: Placebo relief is associated with the release
       of dopamine in the brain.^[89]
     * Depression: Placebos reducing depression affect many of the same
       areas that are activated by antidepressants with the addition of
       the prefrontal cortex^[90]^[91]
     * Caffeine: Placebo-caffeinated coffee causes an increase in
       bilateral dopamine release in the thalamus.^[92]
     * Glucose: The expectation of an intravenous injection of glucose
       increases the release of dopamine in the basal ganglia of men (but
       not women).^[93]
     * Methylphenidate: The expectation of intravenous injection of this
       drug in inexperienced drug users increased the release of dopamine
       in the ventral cingulate gyrus and nucleus accumbens, with this
       effect being largest in those with no prior experience of the
       drug.^[94]

   Present functional imaging upon placebo analgesia has been summarized
   as showing that the placebo response is "mediated by "top-down"
   processes dependent on frontal cortical areas that generate and
   maintain cognitive expectancies. Dopaminergic reward pathways may
   underlie these expectancies".^[95] "Diseases lacking major 'top-down'
   or cortically based regulation may be less prone to placebo-related
   improvement".^[96]

Brain and body[edit]

   For more details on this topic, see neural top down control of
   physiology.

   The brain has control over the body processes affected by placebos.
   Pain, muscle fatigue, and fever are directly organized by the
   brain^[citation needed]. Other processes usually regulated by the body
   such as the immune system are also controlled indirectly through the
   sympathetic and parasympathetic nervous system^[citation needed].

   Research upon conditioning in animals shows the brain can learn control
   over them^[citation needed]. In conditioning, a neutral stimulus
   saccharin is paired in a drink with an agent that produces an
   unconditioned response. For example, that agent might be
   cyclophosphamide that causes immunosuppression. After learning this
   pairing, the taste of saccharin by itself through neural top-down
   control created immunosuppression, as a new conditioned response.^[97]
   Such conditioning has been found to affect a diverse variety of not
   just basic physiological processes in the immune system but ones such
   as serum iron levels, oxidative DNA damage levels, and insulin
   secretion. This work was originally done on rats, however the same
   conditioning of basic physiological processes can also occur in
   humans^[citation needed]. Recent reviews have argued the placebo effect
   is due to top-down control by the brain for immunity^[98] and
   pain.^[99] Pacheco-López and colleagues have raised the possibility of
   "neocortical-sympathetic-immune axis providing neuroanatomical
   substrates that might explain the link between placebo/conditioned and
   placebo/expectation responses."^[98]^:441

   A recent fMRI study has shown that a placebo can reduce pain-related
   neural activity in the spinal cord, indicating that placebo effects can
   extend beyond the brain.^[100]
   Ambox current red.svg
   Parts of this article (those related to PMID 23880289) are outdated.
   Please update this article to reflect recent events or newly available
   information. (December 2013)

Evolved health regulation[edit]

   Evolutionary medicine identifies many symptoms such as fever, pain, and
   sickness behavior as evolved responses to protect or enhance the
   recovery from infection and injury. Fever, for example, is an evolved
   self-treatment that removes bacteria or viruses through raised body
   temperature. These evolved responses, however, also have a cost that
   depending upon circumstances can outweigh their benefit (due to this,
   for example, there is a reduction in fever during malnutrition or late
   pregnancy). According to the health management system theory proposed
   by Nicholas Humphrey, the brain has been selected to ensure that
   evolved responses are deployed only when the cost benefit is
   biologically advantageous. To do this, the brain factors in a variety
   of information sources, including the likelihood derived from beliefs
   that the body will get well without deploying its costly evolved
   responses. One such source of information is the knowledge the body is
   receiving care and treatment. The placebo effect in this perspective
   arises when false information about medications misleads the health
   management system about the likelihood of getting well so that it
   selects not to deploy an evolved self-treatment.^[101]

Clinical utility[edit]

Duration[edit]

   Placebo effects can last for a long time: over 8 weeks for panic
   disorder,^[102] 6 months for angina pectoris,^[103] and two and half
   years for rheumatoid arthritis.^[104] Placebo effects after verbal
   suggestion for mild pain can be robust and still exist after being
   repeated ten times even if they have no actual pharmacological pain
   killing action.^[45]

Clinical significance[edit]

   Hróbjartsson and Peter Gøtzsche published a study in 2001^[10] and a
   follow-up study in 2004^[31] questioning the nature of the placebo
   effect. The studies were performed as two meta-analyses. They found
   that in studies with a binary outcome, meaning patients were classified
   as improved or not improved, the placebo group had no statistically
   significant improvement over the no-treatment group. Likewise, there
   was no significant placebo effect in studies in which objective
   outcomes (such as blood pressure) were measured by an independent
   observer. The placebo effect could be documented only in studies in
   which the outcomes (improvement or failure to improve) were reported by
   the subjects themselves. The authors concluded that the placebo effect
   does not have "powerful clinical effects," (objective effects) and that
   patient-reported improvements (subjective effects) in pain were small
   and could not be clearly distinguished from reporting bias. Other
   researchers (Wampold et al.) re-analysed the same data from the 2001
   meta-analysis and concluded that the placebo effects for objective
   symptom measures are comparable to placebo effects for subjective ones
   and that the placebo effect can exceed the effect of the active
   treatment by 20% for disorders amenable to the placebo
   effect,^[105]^[106] a conclusion which Hróbjartsson & Gøtzsche
   described as "powerful spin".^[107] Another group of researchers noted
   the dramatically different conclusions between these two sets of
   authors despite nearly identical meta-analytic results, and suggested
   that placebo effects are indeed significant but small in
   magnitude.^[108]

   Hróbjartsson and Gøtzsche's conclusion has been criticised on several
   grounds. Their meta-analysis covered studies into a highly mixed group
   of conditions. It has been reported that for measurements in peripheral
   organs the placebo effect seems to be more effective in achieving
   improvements in physical parameters (such as decreasing hypertension,
   improving FEV1 in asthma sufferers, or decreasing prostatic hyperplasia
   or anal fissure) than in improving biochemical parameters (such as
   cholesterol or cortisol) in various conditions such as venous leg
   ulcers, Crohn's disease, urinary tract infection, and chronic heart
   failure.^[109] Placebos also do not work as strongly in clinical trials
   because the subjects do not know whether they might be getting a real
   treatment or a sham one. Where studies are made of placebos in which
   people think they are receiving actual treatment (rather than merely
   its possibility) the placebo effect has been observed.^[110] Other
   writers have argued that the placebo effect can be reliably
   demonstrated under appropriate conditions.^[111]

   In another update by Hróbjartsson & Gøtzsche, published as a 2010
   Cochrane systematic review which confirms and modifies their previous
   work, over 200 trials investigating 60 clinical conditions were
   included. Placebo interventions were again not found to have important
   clinical effects in general but may influence patient-reported outcomes
   in some situations, especially pain and nausea, although it was
   "difficult to distinguish patient-reported effects of placebo from
   response bias". The pooled relative risk they calculated for placebo
   was 0.93 (effect of only 7%) but significant. Effects were also found
   for phobia and asthma but were uncertain due to high risk of bias. In
   other conditions involving three or more trials, there was no
   statistically significant effect for smoking, dementia, depression,
   obesity, hypertension, insomnia and anxiety, although confidence
   intervals were wide. Several clinical (physical placebos,
   patient-involved outcomes, falsely informing patients there was no
   placebo) and methodological (small sample size, explicit aim of
   studying the placebo effect) factors were associated with higher
   effects of placebo. Despite low effects in general and the risk of
   bias, the authors acknowledged that large effects of placebo
   interventions may occur in certain situations.^[112]

Negative effects[edit]

   Similar to the placebo effect, inert substances have the potential to
   cause negative effects via the "nocebo effect" (Latin nocebo = "I will
   harm"). In this effect, giving an inert substance has negative
   consequences.^[113]

   Another negative consequence is that placebos can cause side-effects
   associated with real treatment.^[114] One example of this is with those
   that have already taken an opiate, can then show respiratory depression
   when given it again in the form of a placebo.^[115]

   Withdrawal symptoms can also occur after placebo treatment. This was
   found, for example, after the discontinuation of the Women's Health
   Initiative study of hormone replacement therapy for menopause. Women
   had been on placebo for an average of 5.7 years. Moderate or severe
   withdrawal symptoms were reported by 40.5% of those on placebo compared
   to 63.3% of those on hormone replacement.^[116]

Doctor-patient relationship[edit]

   A study of Danish general practitioners found that 48% had prescribed a
   placebo at least 10 times in the past year.^[5] The most frequently
   prescribed placebos were antibiotics for viral infections, and vitamins
   for fatigue. Specialists and hospital-based physicians reported much
   lower rates of placebo use. A 2004 study in the British Medical Journal
   of physicians in Israel found that 60% used placebos in their medical
   practice, most commonly to "fend off" requests for unjustified
   medications or to calm a patient.^[117] The accompanying editorial
   concluded, "We cannot afford to dispense with any treatment that works,
   even if we are not certain how it does."^[118] Other researches have
   argued that open provision of placebos for treating ADHD in children
   can be effective in maintaining ADHD children on lower stimulant doses
   in the short term.^[119]

   Critics of the practice responded that it is unethical to prescribe
   treatments that do not work, and that telling a patient (as opposed to
   a research test subject) that a placebo is a real medication is
   deceptive and harms the doctor-patient relationship in the long run.
   Critics also argued that using placebos can delay the proper diagnosis
   and treatment of serious medical conditions.^[120]

   The following impracticalities exist with placebos: (See the BMJ posted
   responses to Spiegel's editorial rapid response online section.^[118])
     * Roughly only 30% of the population seems susceptible to placebo
       effects, and it is not possible to determine ahead of time whether
       a placebo will work or not. (However the placebo effect is zero in
       studies of blood poisoning and up to 80% in studies of wound on the
       duodenum).
     * Patients rightfully want immediate relief or improvement from their
       illness or symptoms. A non-placebo can often provide that, while a
       placebo might not.
     * Legitimate doctors and pharmacists could open themselves up to
       charges of fraud since sugar pills would cost pennies or cents for
       a bottle, but the price for a "real" medication would have to be
       charged to avoid making the patient suspicious.

   About 25% of physicians in both the Danish and Israeli studies used
   placebos as a diagnostic tool to determine if a patient's symptoms were
   real, or if the patient was malingering. Both the critics and defenders
   of the medical use of placebos agreed that this was unethical. The
   British Medical Journal editorial said, "That a patient gets pain
   relief from a placebo does not imply that the pain is not real or
   organic in origin...the use of the placebo for 'diagnosis' of whether
   or not pain is real is misguided."

   The placebo administration may prove to be a useful treatment in some
   specific cases where recommended drugs cannot be used. For example,
   burn patients who are experiencing respiratory problems cannot often be
   prescribed opioid (morphine) or opioid derivatives (pethidine), as
   these can cause further respiratory depression. In such cases placebo
   injections (normal saline, etc.) are of use in providing real pain
   relief to burn patients if those not in delirium are told they are
   being given a powerful dose of painkiller.

   Referring specifically to homeopathy, the House of Commons of the
   United Kingdom Science and Technology Committee has stated:

     In the Committee's view, homeopathy is a placebo treatment and the
     Government should have a policy on prescribing placebos. The
     Government is reluctant to address the appropriateness and ethics of
     prescribing placebos to patients, which usually relies on some
     degree of patient deception. Prescribing of placebos is not
     consistent with informed patient choice-which the Government claims
     is very important-as it means patients do not have all the
     information needed to make choice meaningful.

     Beyond ethical issues and the integrity of the doctor-patient
     relationship, prescribing pure placebos is bad medicine. Their
     effect is unreliable and unpredictable and cannot form the sole
     basis of any treatment on the NHS.^[3]

   A survey in the United States of more than 10,000 physicians came to
   the result that while 24% of physicians would prescribe a treatment
   that is a placebo simply because the patient wanted treatment, 58%
   would not, and for the remaining 18%, it would depend on the
   circumstances.^[121]

The individual[edit]

Who is affected[edit]

   Placebos do not work for everyone.^[122]^[123] Henry K. Beecher, in a
   paper in 1955,^[9] suggested placebo effects occurred in about 35% of
   people. However, the response rate is wide, ranging from 0% up to
   nearly everyone. In a dental postoperative pain model, placebo
   analgesia occurred in 39%.^[123] In research upon ischemic arm pain,
   placebo analgesia was found in 27%.^[122] The placebo analgesia rate
   for cutaneous healing of left hand skin was 56%.^[124]

   Though not everyone responds to a placebo, neither does everyone
   respond to an active drug. The percentage of patients who reported
   relief following placebo (39%) is similar to the percentage following
   4 mg (36%) and 6 mg (50%) of hidden morphine.^[125]

Individual differences[edit]

   In the 1950s, there was considerable research to find whether there was
   a specific personality to those that responded to placebos. The
   findings could not be replicated^[126] and it is now thought to have no
   effect.^[127]

   The desire for relief from pain, "goal motivation", and how far pain is
   expected to be relieved increases placebo analgesia.^[71] Another
   factor increasing the effectiveness of placebos is the degree to which
   a person attends to their symptoms, "somatic focus".^[72] Individual
   variation in response to analgesic placebos has been linked to regional
   neurochemical differences in the internal affective state of the
   individuals experiencing pain.^[128]

   Those with Alzheimer's disease lose the capacity to be influenced by
   placebos, and this is attributed to the loss of their prefrontal cortex
   dependent capacity to have expectations.^[129]

   Children seem to have greater response than adults to placebos.^[130]

Genes[edit]

   In social anxiety disorder (SAD) an inherited variant of the gene for
   tryptophan hydroxylase 2 (enzyme that synthesizes the neurotransmitter
   serotonin) is linked to reduced amygdala activity and greater
   susceptibility to the placebo effect.^[131]^[132]^[133] The authors
   note "additional work is necessary to elucidate the generalizability of
   the findings".

   In a 2012 study, variations on the COMT (catechol-O-methyltransferase)
   gene related to dopamine release are found to be critical in the
   placebo effect among the patients with irritable bowel syndrome
   participating in the trial, a research group in Harvard Medical School
   reported. Patients with a variation of met/met, for having two copies
   of the methionine allele were shown to be more likely to respond to the
   placebo treatment, while the variation of val/val, for their two copies
   of valine allele responded the least. The response of patients with one
   copy each of methionine and valine fell in the middle. Release of
   dopamine in patients with the met/met variations is thought to link to
   reward and 'confirmation bias' which enhance the sense that the
   treatment is working. The role of the COMT gene variations are expected
   to be more prominent in studies where patients report more subjective
   conditions such as pain and fatigue rather than objective physiological
   measurements.^[134]^[135]

Symptoms and conditions[edit]

   The placebo effect occurs more strongly in some conditions than others.
   Dylan Evans has suggested that placebos work most strongly upon
   conditions such as pain, swelling, stomach ulcers, depression, and
   anxiety that have been linked with activation of the acute-phase
   response.^[60]

Pain[edit]

   The placebo effect is believed to reduce pain in two different ways.
   One way is by the placebo initiating the release of endorphins, which
   are natural pain killers produced by the brain.^[136] The other way is
   the placebo changing the patient's perception of pain. "A person might
   reinterpret a sharp pain as uncomfortable tingling."^[137]

   Placebo analgesia is more likely to work the more severe the
   pain.^[138] One study found that for postoperative pain following the
   extraction of the third molar, saline injected while telling the
   patient it was a powerful painkiller was as potent as a 6–8 mg dose of
   morphine.^[125] Most research reports average reduction for a group of
   people, but this can be lower (some people do not respond). In one
   study using injection of capsaicin below the skin found that this
   reduced group average pain compared to no placebo by ~46% to ~57%.^[75]
   Another measure is the ability to endure pain. In one study, placebos
   increased this on average by about 3.5 minutes compared to just under
   14 minutes without it.^[139] The average strength of placebos upon pain
   on a visual analog scale is 2 out of 10 units.^[127]^[140] Individuals
   who respond to placebos may show even greater effects, up to 5 out of
   10 units.^[122]

Depression[edit]

   In 1998, a meta-analysis of published antidepressant trials found that
   75% of the effectiveness of anti-depressant medication is due to the
   placebo effect and other non-specific effects, rather than the
   treatment itself.^[141] Later, meta-analyses including data from
   unpublished trials found that the overall difference between drug and
   placebo is not clinically significant except in cases of very extreme
   depression,^[142]^[143] Another meta-analysis found that 79% of
   depressed patients receiving placebo remained well (for 12 weeks after
   an initial 6–8 weeks of successful therapy) compared to 93% of those
   receiving antidepressants.^[144] A meta-analysis in 2002 found a 30%
   reduction in suicide and attempted suicide in the placebo groups
   compared to a 40% reduction in the treated groups.^[145]

   A 2002 article in The Washington Post titled "Against Depression, a
   Sugar Pill Is Hard to Beat" summarized research as follows:

     In the majority of trials conducted by drug companies in recent
     decades, sugar pills have done as well as -- or better than --
     antidepressants. Companies have had to conduct numerous trials to
     get two that show a positive result, which is the Food and Drug
     Administration's minimum for approval. The makers of Prozac had to
     run five trials to obtain two that were positive, and the makers of
     Paxil and Zoloft had to run even more.^[46]

Gastric and duodenal ulcers[edit]

   A meta-study of 31 placebo-controlled trials of the gastric acid
   secretion inhibitor drug cimetidine in the treatment of gastric or
   duodenal ulcers found that placebo treatments, in many cases, were as
   effective as active drugs: of the 1692 patients treated in the 31
   trials, 76% of the 916 treated with the drug were "healed", and 48% of
   the 776 treated with placebo were "healed".^[11]^[146] These results
   were confirmed by the direct post-treatment endoscopy. It was also
   found that German placebos were "stronger" than others; and that,
   overall, different physicians evoked quite different placebo responses
   in the same clinical trial.^[146]^:15 Moreover, in many of these trials
   the gap between the active drugs and the placebo controls was "not
   because [the trials' constituents] had high drug effectiveness, but
   because they had low placebo effectiveness".^[146]^:13

   In some trials, placebos were effective in 90% of the cases, whereas in
   others the placebos were effective in only 10% of the cases. It was
   argued that "what is demonstrated in [these] studies is not enhanced
   healing in drug groups but reduced healing in placebo
   groups".^[146]^:14 It was also noted the results of two studies (one
   conducted in Germany, the other in Denmark), which examined "ulcer
   relapse in healed patients" showed that the rate of relapse amongst
   those "healed" by the active drug treatment was five times that of
   those "healed" by the placebo treatment.^[146]^:14–15

Chronic fatigue syndrome[edit]

   It was previously assumed that placebo response rates in patients with
   chronic fatigue syndrome (CFS) are unusually high, "at least 30% to
   50%", because of the subjective reporting of symptoms and the
   fluctuating nature of the condition. According to a meta-analysis and
   contrary to conventional wisdom, the pooled response rate in the
   placebo group was 19.6%, even lower than in some other medical
   conditions. The authors offer possible explanations for this result:
   CFS is widely understood to be difficult to treat, which could reduce
   expectations of improvement. In context of evidence showing placebos do
   not have powerful clinical effects when compared to no treatment, a low
   rate of spontaneous remission in CFS could contribute to reduced
   improvement rates in the placebo group. Intervention type also
   contributed to the heterogeneity of the response. Low patient and
   provider expectations regarding psychological treatment may explain
   particularly low placebo responses to psychiatric treatments.^[147]

List of medical conditions[edit]

   The effect of placebo treatments (an inert pill unless otherwise noted)
   has been studied for the following medical conditions. Many of these
   citations concern research showing that active treatments are
   effective, but that placebo effects exist as well.
     * ADHD: adult,^[148] child^[119]
     * Amalgam fillings: attributed symptoms (inert "chelation"
       therapy)^[149]
     * Anxiety disorders^[150]^[151]
     * Asthma (water aerosol inhalant)^[152]
     * Asthma^[153]^[154]
     * Autism: language and behavior problems^[155]^[156]
     * Benign prostatic enlargement^[157]
     * Binge eating disorder^[158]
     * Bipolar mania^[159]
     * Cough^[6]

     * Crohn's disease^[160]
     * Depression (light treatment; low red light placebo)^[161]
     * Depression^[141]^[162]^[163]^[164]
     * Dyspepsia and Stomach motility^[165]
     * Epilepsy^[166]
     * Erectile dysfunction^[167]
     * Food allergy: ability to eat ill-making foods^[73] ^p. 54
     * Gastric and duodenal ulcers^[73]^[146]^[168]
     * Headache^[169]
     * Heart failure, congestive^[170]
     * Herpes simplex^[171]

     * Hypertension: mild and moderate^[69]^[172]
     * Irritable bowel syndrome^[173]^[174]
     * Migraine prophylaxis^[175]
     * Multiple sclerosis^[176]
     * Nausea: gastric activity^[177]
     * Nausea: chemotherapy^[178]
     * Nausea and vomiting : postoperative (sham acupuncture)^[179]
     * Pain^[127]^[180]
     * Panic disorders^[181]
     * Parkinson's disease^[182]^[183]
     * Pathological gambling^[184]

     * Premenstrual dysphoric disorder.^[185]
     * Psoriatic arthritis^[186]
     * Reflux esophagitis^[187]
     * Restless leg syndrome^[188]
     * Rheumatic diseases^[189]
     * Sexual dysfunction: women^[190]
     * Social phobia^[191]
     * Third molar extraction swelling (sham ultra-sound)^[13]^[14]
     * Ulcerative colitis^[192]
     * Vulvar vestibulitis^[193]

Effects on research[edit]

Placebo-controlled studies[edit]

   Main article: Placebo-controlled studies

   The placebo effect makes it more difficult to evaluate new treatments.
   The placebo effect in such clinical trials is weaker than in normal
   therapy since the subjects are not sure whether the treatment they are
   receiving is active.^[110] Apparent benefits of a new treatment
   (usually a drug but not necessarily so) may not derive from the
   treatment but from the placebo effect. This is particularly likely,
   given that new therapies seem to have greater placebo effects.^[194]
   Clinical trials control for this effect by including a group of
   subjects that receives a sham treatment. The subjects in such trials
   are blinded as to whether they receive the treatment or a placebo. If a
   person is given a placebo under one name, and they respond, they will
   respond in the same way on a later occasion to that placebo under that
   name but not if under another.^[195] Clinical trials are often
   double-blinded so that the researchers also do not know which test
   subjects are receiving the active or placebo treatment.The placebo
   effect in such clinical trials is weaker than in normal therapy since
   the subjects are not sure whether the treatment they are receiving is
   active.^[110]

   Knowingly giving a person a placebo when there is an effective
   treatment available is a bioethically complex issue. While
   placebo-controlled trials might provide information about the
   effectiveness of a treatment, it denies some patients what could be the
   best available (if unproven) treatment. Informed consent is usually
   required for a study to be considered ethical, including the disclosure
   that some test subjects will receive placebo treatments.

   The ethics of placebo-controlled studies have been debated in the
   revision process of the Declaration of Helsinki.^[196] Of particular
   concern has been the difference between trials comparing inert placebos
   with experimental treatments, versus comparing the best available
   treatment with an experimental treatment; and differences between
   trials in the sponsor's developed countries versus the trial's targeted
   developing countries.^[197]

Nocebo[edit]

   Main article: Nocebo

   In the opposite effect, a patient who disbelieves in a treatment may
   experience a worsening of symptoms. This effect, now called by analogy
   nocebo (Latin nocebo = "I shall harm") can be measured in the same way
   as the placebo effect, e.g., when members of a control group receiving
   an inert substance report a worsening of symptoms. The recipients of
   the inert substance may nullify the placebo effect intended by simply
   having a negative attitude towards the effectiveness of the substance
   prescribed, which often leads to a nocebo effect, which is not caused
   by the substance, but due to other factors, such as the patient's
   mentality towards his or her ability to get well, or even purely
   coincidental worsening of symptoms.^[113]

Placebo ingredients[edit]

   Placebos used in clinical trials have sometimes had unintended
   consequences. A report in the Annals of Internal Medicine that looked
   at details from 150 clinical trials found that certain placebos used in
   the trials affected the results. For example, one study on
   cholesterol-lowering drugs used olive oil and corn oil in the placebo
   pills. However, according to the report, this "may lead to an
   understatement of drug benefit: The monounsaturated and polyunsaturated
   fatty acids of these 'placebos,' and their antioxidant and
   anti-inflammatory effects, can reduce lipid levels and heart disease."
   Another example researchers reported in the study was a clinical trial
   of a new therapy for cancer patients suffering from anorexia. The
   placebo that was used included lactose. However, since cancer patients
   typically face a higher risk of lactose intolerance, the placebo pill
   might actually have caused unintended side-effects that made the
   experimental drug look better in comparison.^[198]

See also[edit]

     * Self-fulfilling prophecy

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External links[edit]

   Look up placebo in Wiktionary, the free dictionary.
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     * Harvard-wide Program in Placebo Studies & the Therapeutic Encounter
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     * The Placebo Effect explained on YouTube
     * Placebos: cracking the code part 1 part 2 BBC/Discovery channel
       program
     * "Placebos are getting more effective. Drugmakers are desperate to
       know why." Wired magazine on the power of the placebo. Retrieved
       2010-07-22
     * Biological, clinical, and ethical advances of placebo effects The
       Lancet (2010)

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    1. H. K. Beecher
    2. false placebo
    3. Hróbjartsson and Götzsche
    4. placebos and pain relief
    5. "it's all in your mind"
    6. process-of-treatment belief
    7. ethical dilemma
    8. the genetic connection
    9. are placebos dangerous?
    10. list of other Skeptic's Dictionary entries of relevance to the
   placebo effect
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placebo effect

     "The physician's belief in the treatment and the patient's faith in
     the physician exert a mutually reinforcing effect; the result is a
     powerful remedy that is almost guaranteed to produce an improvement
     and sometimes a cure." -- Petr Skrabanek and James McCormick,
     Follies and Fallacies in Medicine, p. 13.

   The placebo effect is the measurable, observable, or felt improvement
   in health or behavior not attributable to a medication or invasive
   treatment that has been administered. The placebo effect is not mind
   over matter; it is not mind-body medicine. 'The placebo effect' has
   become a catchall term for a positive change in health not attributable
   to medication or treatment. As is explained below, the change can be
   due to many things, such as regression to the mean, spontaneous
   improvement, reduction of stress, misdiagnosis in the first place,
   subject expectancy, classical conditioning, etc.

   A placebo (Latin for "I shall please") is a pharmacologically inert
   substance (such as saline solution or a starch tablet) that seems to
   produce an effect similar to what would be expected of a
   pharmacologically active substance (such as an antibiotic).

   By extension, "fake" surgery and "fake" therapies are considered
   placebos.

   The idea of the placebo in modern times originated with H. K. Beecher.
   He evaluated 15 clinical trials concerned with different diseases and
   found that 35% of 1,082 patients were satisfactorily relieved by a
   placebo alone ("The Powerful Placebo," 1955). Other studies have since
   calculated the placebo effect as being even greater than Beecher
   claimed. For example, studies have shown that placebos are effective in
   50 or 60 percent of subjects with certain conditions, e.g., "pain,
   depression, some heart ailments, gastric ulcers and other stomach
   complaints."* And, as effective as the new psychotropic drugs seem to
   be in the treatment of various brain disorders, some researchers
   maintain that there is not adequate evidence from studies to prove that
   the new drugs are more effective than placebos.

   Beecher started a wave of studies aimed at understanding how something
   (improvement in health) could be produced by nothing (the inactive
   placebo). Unfortunately, many of the studies have not been of
   particularly high quality and have assumed that any measured
   improvement was caused by the placebo. In fact, it has been argued by
   Kienle and Kiene (1997) that, contrary to what Beecher claimed, a
   reanalysis of his data found "no evidence of any placebo effect in any
   of the studies cited by him." The reported improvements in heath were
   real but were due to other things that produced "false impressions of
   placebo effects." The reanalysis of Beecher's data claims that the
   improvements were due to:

     Spontaneous improvement, fluctuation of symptoms, regression to the
     mean, additional treatment, conditional switching of placebo
     treatment, scaling bias, irrelevant response variables, answers of
     politeness, experimental subordination, conditioned answers,
     neurotic or psychotic misjudgment, psychosomatic phenomena,
     misquotation, etc.

   What the reanalysis shows is that there are a number of factors that
   can affect many treatments and the evaluation of those treatments,
   making it very difficult to be sure just what it is about an
   intervention that produces improvement or perceived improvement. We
   must also consider "artifacts such as the natural history of a disease
   (that is, the tendency for people to get better or worse during the
   course of an illness irrespective of any treatment at all), the fact
   that people behave differently when they are participating in an
   experiment than when they are not, a desire to please the experimental
   staff by providing socially desirable answers..." (Bausell 2007: 27),
   and a host of other factors unrelated to the pill we are administering
   and independently of any mechanism that we believe is producing any
   observed effects.

   In May 2001, The New England Journal of Medicine published an article
   that called into question the validity of the placebo effect. "Is the
   Placebo Powerless? An Analysis of Clinical Trials Comparing Placebo
   with No Treatment" by Danish researchers Asbjørn Hróbjartsson and Peter
   C. Götzsche "found little evidence in general that placebos had
   powerful clinical effects." Their meta-analysis of 114 studies found
   that "compared with no treatment, placebo had no significant effect on
   binary outcomes, regardless of whether these outcomes were subjective
   or objective. For the trials with continuous outcomes, placebo had a
   beneficial effect, but the effect decreased with increasing sample
   size, indicating a possible bias related to the effects of small
   trials." (Most of the studies evaluated by Hróbjartsson and Götzsche
   were small: for 82 of the studies the median size was 27 and for the
   other 32 studies the median was 51.)

   "The high levels of placebo effect which have been repeatedly reported
   in many articles, in our mind are the result of flawed research
   methodology," said Dr. Hróbjartsson, professor of medical philosophy
   and research methodology at the University of Copenhagen.*

   Typical of the kind of flawed research methodology Hróbjartsson is
   referring to would be that of surgeon J. Bruce Moseley who performed
   fake knee surgery on eight of ten patients. (Fake surgery involves
   making an incision on the knee and stitching it up.) Six months after
   the surgery all the patients were satisfied customers. Rather than
   conclude that the patients didn't need surgery or that the surgery was
   useless because in time the patients would have healed on their own, he
   and others concluded that the healing of the eight who did not have
   surgery was due to the placebo effect, while the two who had real
   surgery were better because of having had the operation. Irving Kirsch
   and Guy Sapirstein have been accused of making the same kind of
   methodological error in their controversial meta-analysis that found
   that anti-depressants work by the placebo effect, rather than that
   anti-depressants are unnecessary and useless.

   One more example should suffice to make the point that better designs
   of placebo studies are needed.

     Forty years ago, a young Seattle cardiologist named Leonard Cobb
     conducted a unique trial of a procedure then commonly used for
     angina, in which doctors made small incisions in the chest and tied
     knots in two arteries to try to increase blood flow to the heart. It
     was a popular technique—90 percent of patients reported that it
     helped—but when Cobb compared it with placebo surgery in which he
     made incisions but did not tie off the arteries, the sham operations
     proved just as successful. The procedure, known as internal mammary
     ligation, was soon abandoned ("The Placebo Prescription" by Margaret
     Talbot, New York Times Magazine, January 9, 2000).*

   Did Cobb show that this kind of surgery works by the placebo effect? Or
   did he show that the surgery was unnecessary because most of the
   patients would have healed on their own if nothing had been done?

   To rule out the natural history of a disease or regression to the mean,
   many researchers have used a third control group—those who receive no
   treatment at all. If the placebo group shows better results than the
   group getting nothing, then surely the placebo is effective.
   Hróbjartsson and Götzsche think most of these studies, too, are flawed,
   mainly due to having samples that are too small or due to patients who
   make reports aimed at pleasing the researcher.

   After the publication of the Hróbjartsson and Götzsche study, Dr. John
   C. Bailar III said in an editorial that accompanied the study: "The
   shoe is on the other foot now. The people who claim there are placebo
   effects are going to have to show it." The need, he said, is for large,
   rigorously designed studies that clearly define and measure effects of
   drugs and therapies versus placebos versus no intervention at all.
   These studies will have to clearly distinguish objective measurements
   (such as blood pressure, cholesterol levels, etc.) and subjective
   measurements (such as reports of pain or evaluative sensory
   observations by researchers, e.g., "I can see your tumor is smaller" or
   "I can see you are not as depressed as before").

   The kind of study called for by Dr. Bailar has been done and several
   such studies are reviewed in chapter nine of R. Barker Bausell's Snake
   Oil Science (2007): "How We Know That the Placebo Effect Exists." One
   in particular is worth reviewing here. It was published in the Journal
   Pain two months after the Hróbjartsson and Götzsche article. "Response
   expectancies in placebo analgesia and their clinical relevance" was the
   work of Antonella Pollo et al. and demonstrated that placebos can help
   people with serious pain. The following is from their abstract:

     Thoracotomized patients were treated with buprenorphine [a powerful
     pain reliever] on request for 3 consecutive days, together with a
     basal intravenous infusion of saline solution. However, the symbolic
     meaning of this basal infusion was changed in three different groups
     of patients. The first group was told nothing about any analgesic
     effect (natural history). The second group was told that the basal
     infusion was either a powerful painkiller or a placebo (classic
     double-blind administration). The third group was told that the
     basal infusion was a potent painkiller (deceptive administration).
     Therefore, whereas the analgesic treatment was exactly the same in
     the three groups, the verbal instructions about the basal infusion
     differed. The placebo effect of the saline basal infusion was
     measured by recording the doses of buprenorphine requested over the
     three-days treatment. We found that the double-blind group showed a
     reduction of buprenorphine requests compared to the natural history
     group. However, this reduction was even larger in the deceptive
     administration group. Overall, after 3 days of placebo infusion, the
     first group received 11.55 mg of buprenorphine, the second group
     9.15 mg, and the third group 7.65 mg. Despite these dose
     differences, analgesia was the same in the three groups. These
     results indicate that different verbal instructions about certain
     and uncertain expectations of analgesia produce different placebo
     analgesic effects, which in turn trigger a dramatic change of
     behaviour leading to a significant reduction of opioid intake.

   The patients who thought their IV contained a powerful pain reliever
   required 34% less of the analgesic than the patients who weren't told
   anything about their IV and 16% less than the patients who were told
   the IV could be either a powerful pain killer or a placebo. Each group
   got exactly the same amount of pain killer but their requests for the
   analgesic differed dramatically. The only significant difference among
   the three groups was the set of verbal instructions about the basal
   infusion. The study was too short for the differences to be explained
   by the natural history of recovery, regression, or any of the other
   alternatives found by Hróbjartsson and Götzsche.

   Several things are worth noting about this experiment. The setting
   involves treatment being provided by medical personnel in a medical
   facility. This kind of setting usually involves a strong desire for
   recovery or relief on the part of the patient, as well as a belief that
   the treatment will be effective. The different verbal instructions
   about the basal IV would lead to different expectations. Belief,
   motivation, and expectation are essential to some forms of the placebo
   effect. Together, they are referred to as the subject-expectancy
   effect. Classical conditioning  and suggestion by an authoritative
   healer seem to be triggering mechanisms for [DEL: the :DEL] this form
   of placebo effect (Bausell 2007: 131).

             the psychological hypothesis: it's all in your mind

   Some believe the placebo effect is purely psychological. Irving Kirsch,
   a psychologist at the University of Connecticut, believes that the
   effectiveness of Prozac and similar drugs may be attributed almost
   entirely to the placebo effect. He and Guy Sapirstein analyzed 19
   clinical trials of antidepressants and concluded that the expectation
   of improvement, not adjustments in brain chemistry, accounted for 75
   percent of the drugs' effectiveness (Kirsch 1998).  "The critical
   factor," says Kirsch, "is our beliefs about what's going to happen to
   us. You don't have to rely on drugs to see profound transformation." In
   an earlier study, Sapirstein analyzed 39 studies, done between 1974 and
   1995, of depressed patients treated with drugs, psychotherapy, or a
   combination of both. He found that 50 percent of the drug effect is due
   to the placebo response.

   A person's beliefs and hopes about a treatment, combined with their
   suggestibility, may have a significant biochemical effect, however.
   Sensory experience and thoughts can affect neurochemistry. The body's
   neurochemical system affects and is affected by other biochemical
   systems, including the hormonal and immune systems. Thus, it is
   consistent with current knowledge that a person's hopeful attitude and
   beliefs may be very important to their physical well-being and recovery
   from injury or illness. But it does not follow from this fact that if
   the patient has hope will she recover. Nor does it follow from this
   fact that if a person is not hopeful she will not recover.

   The psychological explanation seems to be the one most commonly
   believed. Perhaps this is why many people are dismayed when they are
   told that the effective drug they are taking is a placebo. This makes
   them think that their problem is "all in their mind" and that there is
   really nothing wrong with them. Yet, there are too many studies that
   have found objective improvements in health after being given placebos
   to support the notion that the placebo effect is entirely
   psychological.

     Doctors in one study successfully eliminated warts by painting them
     with a brightly colored, inert dye and promising patients the warts
     would be gone when the color wore off. In a study of asthmatics,
     researchers found that they could produce dilation of the airways by
     simply telling people they were inhaling a bronchodilator, even when
     they weren't. Patients suffering pain after wisdom-tooth extraction
     got just as much relief from a fake application of ultrasound as
     from a real one, so long as both patient and therapist thought the
     machine was on. Fifty-two percent of the colitis patients treated
     with placebo in 11 different trials reported feeling better -- and
     50 percent of the inflamed intestines actually looked better when
     assessed with a sigmoidoscope ("The Placebo Prescription" by
     Margaret Talbot, New York Times Magazine, January 9, 2000).*

   It is unlikely that such effects are purely psychological, though I
   must admit that I don't find the expression 'purely psychological' very
   precise or clear.

   In fact, Martina Amanzio et al. (2001) demonstrated that "at least part
   of the physiological basis for the placebo effect is opioid in nature"
   (Bausell 2007: 160). We can be conditioned to release such chemical
   substances as endorphins, catecholamines, cortisol, and adrenaline. One
   reason, therefore, that people report pain relief from both acupuncture
   and sham acupuncture [DEL: is :DEL] may be that both are placebos that
   stimulate the opioid system.

                       the process-of-treatment belief

   Another popular belief is that a process of treatment that involves
   showing attention, care, affection, etc., to the patient/subject, a
   process that is encouraging and hopeful, may itself trigger physical
   reactions in the body which promote healing. According to Dr. Walter A.
   Brown, a psychiatrist at Brown University:

     ...there is certainly data that suggest that just being in the
     healing situation accomplishes something. Depressed patients who are
     merely put on a waiting list for treatment do not do as well as
     those given placebos. And—this is very telling, I think—when
     placebos are given for pain management, the course of pain relief
     follows what you would get with an active drug. The peak relief
     comes about an hour after it's administered, as it does with the
     real drug, and so on. If placebo analgesia was the equivalent of
     giving nothing, you'd expect a more random pattern ("The Placebo
     Prescription" by Margaret Talbot, New York Times Magazine, January
     9, 2000).*

   Dr. Brown and others believe that the placebo effect is mainly or
   purely physical and due to physical changes that promote healing or
   feeling better.

   So, what is the explanatory mechanism for the placebo effect? Some
   think it is the process of administering it. It is thought that the
   touching, the caring, the attention, and other interpersonal
   communication that is part of the controlled study process (or the
   therapeutic setting), along with the hopefulness and encouragement
   provided by the experimenter/healer, affect the mood, expectations, and
   beliefs of the subject, which in turn triggers physical changes such as
   release of endorphins, catecholamines, cortisol, or adrenaline. The
   process reduces stress by providing hope or reducing uncertainty about
   what treatment to take or what the outcome will be. The reduction in
   stress prevents or slows down further harmful physical changes from
   occurring. The healing situation provokes a conditioned response. The
   patient's been healed before by the doctor (or thinks she's been healed
   before by the doctor) and expects to be healed again.

   the genetic connection

   Because the placebo effect shows profound variability among
   individuals, some researchers have looked for evidence of a genetic
   predisposition to susceptibility to placebo effects. Andrew Leuchter et
   al. postulated that placebos act through central reward pathways
   modulated by monoamines, which are under strong genetic control. Their
   findings "support the hypothesis that genetic polymorphisms modulating
   monoaminergic tone are related to degree of placebo responsiveness in
   major depressive disorder."* The researchers stressed that genetics is
   not the sole explanation for a placebo response, which is likely to be
   influenced by several biological and psychosocial factors.*

                             the ethical dilemma

   The power of the placebo effect has led to an ethical dilemma. One
   should not deceive other people, but one should relieve the pain and
   suffering of one's patients. Should one use deception to benefit one's
   patients? Is it unethical for a doctor to knowingly prescribe a placebo
   without informing the patient? If informing the patient reduces the
   effectiveness of the placebo, is some sort of deception warranted in
   order to benefit the patient? Some doctors think it is justified to use
   a placebo in those types of cases where a strong placebo effect has
   been shown and where distress is an aggravating factor.*  Others think
   it is always wrong to deceive the patient and that informed consent
   requires that the patient be told that a treatment is a placebo
   treatment. Others, especially complementary and alternative medicine
   (CAM) practitioners, don't even want to know whether a treatment is a
   placebo or not. Their attitude is that as long as the treatment is
   effective, who cares if it a placebo? This attitude is changing,
   however, and it is now common to find defenders of CAM admit that CAM
   is placebo medicine and go on to claim that that's why CAM is good
   medicine!

   While it may be unethical to knowingly package, prescribe, or sell
   placebos as magical cures, the CAM folks seem to think they are ethical
   because they really believe in their chi, meridians, yin, yang, prana,
   vata, pitta, kapha, auras, chakras, energies, spirits, succussion,
   natural herbs, water with precise and selective memory, subluxations,
   cranial and vertebral manipulations, douches and irrigations, body
   maps, divinities, and various unobservable processes that allegedly
   carry out all sorts of magical analgesic and curative functions.

                           are placebos dangerous?

   While skeptics may reject faith, prayer and "alternative" medical
   practices such as bioharmonics, chiropractic, and homeopathy, such
   practices may not be without their salutary effects. Clearly, they
   can't cure cancer or repair a punctured lung, and they might not even
   prolong life by giving hope and relieving distress as is sometimes
   thought. But administering placebo therapies does involve interacting
   with the patient in a caring, attentive way, and this can provide some
   measure of comfort. However, to those who say "what difference does it
   make why something works, as long as it seems to work" I reply that it
   is likely that there is something that works even better and might even
   be cheaper. Worse, some people might seek out an alternative healer for
   a serious disorder that isn't affected by the CAM treatment but could
   be relieved or cured by scientific medicine. Furthermore, placebos may
   not always be beneficial or harmless. John Dodes notes:

     Patients can become dependent on nonscientific practitioners who
     employ placebo therapies. Such patients may be led to believe
     they're suffering from imagined "reactive" hypoglycemia, nonexistent
     allergies and yeast infections, dental filling amalgam "toxicity,"
     or that they're under the power of qi or extraterrestrials. And
     patients can be led to believe that diseases are only amenable to a
     specific type of treatment from a specific practitioner (The
     Mysterious Placebo by John E. Dodes, Skeptical Inquirer, Jan/Feb
     1997).

   In other words, the placebo can be an open door to malfeasance.  R.
   Barker Bausell speculates that since complementary and alternative
   medicine (CAM) practitioners' greatest asset is their nourishment of
   hope (2007: 294), "such therapies may be engendering nothing more than
   the expectation that they will reduce pain by elaborate explanations,
   promises, and ceremonies" (p. 149). Packaging placebos is big business
   and is likely to get even bigger. The only thing that could slow down
   CAM atavism would be the sudden appearance of horrible side effects
   issuing from treatments like aura cleansings or homeopathic douches.

   I'd say that there's about as much chance of that happening as there is
   of John Edward or James Van Praagh announcing to an audience that a
   spirit is telling him that one of the paying customers is an axe
   murderer.

   See also conditioning, confirmation bias, control study, communal
   reinforcement, magical thinking, nocebo, Occam's razor, post hoc
   fallacy, regressive fallacy, selective thinking, self-deception,
   subjective validation, testimonials, and wishful thinking.

   For examples of beliefs deeply affected by the placebo effect see the
   following entries in The Skeptic's Dictionary:

     * acupuncture
     * alphabiotics
     * angel therapy
     * animal quacker
     * anthroposophic medicine
     * applied kinesiology
     * aromatherapy
     * astrotherapy
     * aura therapy
     * Ayurvedic medicine
     * Bach's flower therapy
     * bio-ching
     * bioharmonics
     * chelation therapy
     * chiropractic
     * complex homeopathy
     * coning (ear candling)
     * Consegrity
     * craniosacral therapy
     * DHEA
     * dolphin-assisted therapy
     * Dr. Fritz - "energy healing"
     * Eye Movement Desensitization Reprocessing (EMDR)
     * facilitated communication
     * faith healing
     * healing touch
     * homeopathy
     * hypnotherapy
     * iridology
     * joy touch
     * magnet therapy
     * microacupuncture
     * naturopathy
     * osteopathy
     * prayer
     * psychic surgery
     * reflexology
     * reiki
     * therapeutic touch
     * trepanation
     * urine therapy
   _________________

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   further reading

   books and articles

   Amanzio Martina et al. (2001). Response variability to analgesics: a
   role for non-specific activation of endogenous opioids. Pain. Feb
   15;90(3):205-15.

   Bausell, R. Barker. (2007). Snake Oil Science: The Truth about
   Complementary and Alternative Medicine Oxford.

   Dodes, John E. (1997). The Mysterious Placebo. Skeptical Inquirer.

   Engel, Linda W. et al. The Science of the Placebo - Toward an
   Interdisciplinary Research Agenda ( BMJ Books, 2002).

   Fisher, Seymour and Roger P. Greenberg. eds. From Placebo to Panacea:
   Putting Psychiatric Drugs to the Test (John Wiley and Sons, 1997).

   Hart, Carol. The Mysterious Placebo Effect. Modern Drug Discovery
   July/August 1999

   Hróbjartsson, Asbjørn and Peter C. Götzsche. "Is the Placebo Powerless?
   An Analysis of Clinical Trials Comparing Placebo with No Treatment,"
   The New England Journal of Medicine, May 24, 2001 (Vol. 344, No. 21).
   Abstract.

   Harrington, Anne. ed. The Placebo Effect : An Interdisciplinary
   Exploration (Harvard University Press, 1999).

   Jerome, Lawrence E. Crystal Power - The Ultimate Placebo Effect
   (Amherst, NY: Prometheus, 1996).

   Kaptchuk, Ted J. et al. Components of placebo effect: randomised
   controlled trial in patients with irritable bowel syndrome. British
   Medical Journal, May 2008

   Kirsch, Irving , Ph.D. and Guy Sapirstein, Ph.D. "Listening to Prozac
   but Hearing Placebo: A Meta-Analysis of Antidepressant Medication"
   Prevention & Treatment, Volume 1, June 1998.

   Moerman, Daniel E.  (2002). Meaning, Medicine and the 'Placebo Effect'.
   Cambridge University Press.

   Ogelsby, Dr. Paul. The Caring Physician : The Life of Dr. Francis W.
   Peabody (Harvard University Press, 1991).

   Price, D. D. et al. (1999). An analysis of factors that contribute to
   the magnitude of placebo analgesia in an experimental paradigm. Pain,
   Volume 83, Number 2.

   Price, Donald D. et al. (2005). Conditioning, expectation, and desire
   for relief in placebo analgesia. Seminars in Pain Medicine. Volume 3,
   Issue 1. Abstract.

   Skrabanek, Petr, and James McCormick, (1990). Follies & Fallacies in
   Medicine. Prometheus.

   Sternberg, Esther M. and Philip W. Gold. "The Mind-Body Interaction in
   Disease," Scientific American," special issue "Mysteries of the Mind,"
   (January 1997).

   Shapiro, Arthur K. and Elaine Shapiro. The Powerful Placebo: From
   Ancient Priest to Modern Physician (Johns Hopkins University Press,
   1997).

   Stanovich, Keith E. How to Think Straight About Psychology, 3rd ed.,
   (New York: Harper Collins, 1992).

   Thompson, W. Grant. (2005). The Placebo Effect and Health:  Combining
   Science and Compassionate Care. Prometheus.

   Watts, Geoff. The power of nothing. New Scientist

   White, Leonard, Bernard Tursky and Gary Schwartz. Placebo: Theory
   Research, and Mechanisms, ed.  (New York: Guilford Press, 1985).

   websites & blogs

   Several posts by Orac at Respectful Insolence and his evil twin David
   Gorski at Science-Based Medicine go into great detail about how CAM
   defenders have co-opted so-called placebo medicine.

     Placebo effects are "proof" that God [sic] exists? Yes, someone has
     made this argument and posted it on the Huffington Post

     Adventures in defending science-based medicine in cancer journals:
     Energy chelation

     Does thinking make it so?

     CAM, placebos, and the new paternalism

     Credulous reporting on placebo effects strikes again

   Also, Stephen Novella, M.D., has posted this piece: American Headache
   Society Recommends Placebos for Migraine The placebo in question is
   acupuncture.

   Transcript of BRAIN SCIENCE PODCAST With Ginger Campbell, MD Episode
   #77 Originally Aired 9/19 /2011 Interview with Fabrizio Benedetti, MD,
   PhD, Author of Placebo Effects: Understanding the Mechanisms in Health
   and Disease, and The Patient’s Brain: The Neuroscience behind the
   Doctor-Patient Relationship

   What's in a placebo? Mike Adams certainly doesn't know "...the real
   difference between skeptics and pseudoskeptics is that skeptics base
   their skepticism on science and evidence. Pseudoskeptics like Mike
   Adams do not; rather, they base it in ideology.

   What’s In Placebos? by Steven Novella, M.D. "A new study in the Annals
   of Internal Medicine reviews clinical trials over the last two years.
   They found that only 8.2% of clinical trials with a placebo pill as a
   control specifically disclosed the placebo content. Meanwhile 26.7% of
   trials involving injections and procedures disclosed the precise nature
   of the treatment."

   To see the abstract of the study, click here.

   Prescribing Placebos by R. T. Carroll

   My review of Snake Oil Science

   Placebo Effects Revisited by Steven Novella Existing evidence strongly
   suggests that placebo effects are mostly comprised of bias in reporting
   and observation and non-specific effects. There is no measurable
   physiological benefit from placebo interventions for any objective
   outcome. There is a measured benefit for some subjective outcomes
   (mostly pain, nausea, asthma, and phobias), but the wide variation in
   effect size suggests this is due to trial design (and therefore bias)
   rather than a real effect.

   The Placebo Effect by Steven Novella

   "Placebo Effect Accounts For Fifty Percent Of Improvement In Depressed
   Patients Taking Antidepressants" by the American Psychological
   Association

   Not treating - a neglected option by Harriet Hall

   Ben Goldacre on the placebo effect

   news stories

   Irritable Bowel Syndrome: Placebo Works Even if Patients Know
   "Incredibly, according to a new study of patients with irritable bowel
   syndrome, the placebo effect, even when patients were in on the secret,
   worked almost as well as the leading medication on the market....After
   three weeks. the placebo group reported adequate symptom relief at
   double the rate of the group told to do nothing (59 percent vs. 35
   percent). And those results are about as good as the leading irritable
   bowel syndrome drugs on the market. Researchers sounded the usual
   cautionary notes. The study was small. It's not clear what it would
   mean for other conditions and more research is needed."

   Even so, the study supports the notion that the leading IBS medication
   is a placebo. Since many cases of IBS are stress-related, it makes
   sense that placebos would work well here if the process of
   administering them reduces stress. There's a lot the article doesn't
   cover. For a thorough analysis, see Respectful Insolence's take on this
   study. Or, better yet, look at the article on PLoS ONE: Placebos
   without Deception: A Randomized Controlled Trial in Irritable Bowel
   Syndrome

   The magic cure "There are limits to even the strongest placebo effect.
   No simulation could set a broken arm, of course, or clear a blocked
   artery. As a rule, placebos appear to affect symptoms rather than
   underlying diseases--although sometimes, as in the case of depression
   or irritable bowel syndrome, there’s no meaningful distinction between
   the two. Moreover, placebos have often received undue credit for
   recovery that might have occurred anyway. Indeed, the effect is
   famously difficult to identify, measure, and even coherently define.
   There is debate about the magnitude of the response, with some calling
   it modest at best, and opposing the idea of using placebos clinically."

   “Connecting with the patient, rapport, empathy . . . that few extra
   minutes is not just icing on the cake. It has biology.”

   Placebos: Pretty Good for Depression A meta-analysis published in JAMA
   confirmed what several other studies have found: anti-depressants are
   placebos for all but the severely depressed. The authors of the study
   concluded: the average benefit of antidepressant medication in patients
   with mild or moderate symptoms of depression is minimal. "The mere act
   of seeing a doctor, discussing symptoms and learning about depression
   probably triggers the improvements many patients experience while on
   medication."* (See next two entries, please.)

   Before You Quit Antidepressants ... The study is a so-called
   meta-analysis — not a fresh clinical trial....For the recent analysis
   in the journal, the authors identified 23 studies (out of several
   hundred clinical trials) that met their criteria for inclusion. Of
   those 23, they could get access to data on only 6, with a total of 718
   subjects....That is not many studies if your goal is to answer a broad
   question about the efficacy of antidepressants as a class.

   Study shows antidepressants useless for mild to moderate depression?
   Not exactly. - Science-Based Medicine - "...the paper included only 3
   studies of an SSRI. How did the authors whittle down thousands of
   papers on SSRI effectiveness to only 3?...by using questionable
   exclusion criteria, the authors accessed only 3 clinically relevant
   studies (the Paxil studies), involving only one SSRI. It is not clear
   that these studies are representative of existing studies on SSRIs, or
   even if they can be generalized to other SSRIs." (See also Science by
   Press Release.)

   MEDIA WATCH Antidepressant-Placebo Debate in the Media Balanced
   Coverage or Placebo Hype?

   German study on the placebo effect hyped by mediaThis is about a report
   in Science. The study had only 15 participants, all men. It involved
   doing an fMRI of their spinal columns while applying different degrees
   of heat to their arms, which had been treated with an analgesic or a
   placebo. Some of these stories seem to think the study is
   groundbreaking because it shows that the placebo effect is not all in
   the head. We already knew that from numerous studies. Some claim that
   the study proves spinal inhibition is one of the mechanisms by which
   the placebo effect reduces pain. No, it doesn't. The study is too small
   to prove anything. It needs to be replicated with larger groups and
   with some extensions to make sure the fMRI readings are caused by the
   placebo and indicate what the researchers think they indicate.

   A Doctor for Disease, a Shaman for the Soul Mercy Medical Center in
   Merced figured it was healthier to bring them in rather than shut them
   out, so it invited the many Hmong shamans who dwell in California's
   central valley to learn about medicine in exchange for allowing the
   shamans to treat spirits in the hospital. Superstition and science work
   hand-in-hand in more than 60 hospitals in the United States in an
   effort to accommodate cultural beliefs and break down barriers that
   keep many people from seeking treatment for their serious health
   problems.

   Placebos Are Getting More Effective. Drugmakers Are Desperate to Know
   Why. By Steve Silberman. Wired. 24 Aug 2009. [The article is worth
   reading but the blinking ad on the right might drive you away. Shrink
   your viewing window to block out the annoying ad.] First, the facts: an
   increasing number of new medications are unable to beat sugar pills in
   RCTs (randomized control studies); trials done in different cultures
   get different placebo responses; and those of us subjected to constant
   advertising of pills for every ailment under the sun packaged with
   stories from satisfied customers are being conditioned to expect relief
   for our ailments from a pill. It is, of course, possible that the
   effectiveness of new drugs versus placebos is decreasing because the
   clinical trials are getting better or the new medications are less
   effective. There have been studies that have found that certain persons
   are more susceptible to placebos than others. What is intriguing is
   that there has been very little study on the cultural influences that
   affect placebo response. More intriguing is the role of cultural
   conditioning on susceptibility to placebo effect. Though some laugh at
   the idea of the placebo effect increasing, it is possible that through
   social conditioning more and more people could become more affected by
   placebo medicine (including the theater, the suggestions, and all the
   other things that are lumped together under the 'placebo effect').

   Placebo medicine to be offered by NHS in Northern Ireland Homeopathy,
   acupuncture, and reflexology are among a range of placebo therapies a
   new trial concludes should be provided by the NHS. "As many as 81% of
   patients receiving the treatments on referral from their GP reported
   improvements in their physical health, and 79% in their mental health."
   It will save money, too.

   First 'placebo gene' discovered

   The placebo effect is the healing force of nature by G. Zajicek

   The Placebo Prescription - New York Times Magazine 1/09/2000

   Sham Surgery Returns as a Research Tool by Sheryl Gay Stolberg, New
   York Times 4/25/1999

   A surprisingly potent placebo: face time with me by Dr. Michael Evans

   Researchers Debunk Placebo Effect, Saying It's Only a Myth by Gina
   Kolata (NY Times)

   Half of Doctors Routinely Prescribe Placebos

   Placebos Recommended Routinely By Doctors

   Scientists See How Placebo Effect Eases Pain - Scientific American

   "Against Depression, a Sugar Pill Is Hard to Beat Placebos Improve
   Mood, Change Brain Chemistry in Majority of Trials of Antidepressants"
   by Shankar Vedantam

   Last updated 29-Dec-2013

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How the Placebo Effect Works

   by Shanna Freeman
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     Page

     1
   Introduction to How the Placebo Effect Works

     2
   Placebos: Is It All in Your Head?

     3
   Placebos in Research

     4

   Prescribing Placebos

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     * DiscoveryHealth.com: Pros/Cons of Placebos

   Most of us only go to the doctor when we're not feeling well. You read
   old magazines in the waiting room, pony up your insurance company's
   co-pay, answer a stream of seemingly endless questions, and put up with
   being poked and prodded. And for enduring all of this, you expect
   something in return. More often than not, that something is a piece of
   paper with a prescription scrawled on it. You don't usually worry much
   about what's in the medicine that the doctor has prescribed, as long as
   it gets you feeling like yourself again. You trust that the doctor
   knows what's best.

   But how much does that trust play into the healing process? What if,
   after filling that prescription and taking it faithfully, you found out
   that the medicine your doctor had given you wasn't proven to make you
   feel better? And yet you did get better. You expected to get well after
   taking those pills, so you did.

   That's the gist of the placebo effect. It's what happens when a person
   takes a medication that he or she perceives will help, although it
   actually has no proven therapeutic effect for his or her particular
   condition. The medicine or treatment itself is known as a placebo, from
   Latin for "I will please." There are a few different types of placebos.
   They may be pharmacologically inert, meaning that they contain no
   active ingredients. These types of placebos often contain basic
   ingredients like sugar (hence the term "sugar pill"). Medications that
   do have active ingredients but aren't proven to work on the patient's
   particular condition can also be placebos. There have even been
   placebos in the form of surgery, injections and other types of medical
   therapies. Some people believe that complementary and alternative
   medicine count as placebos, too.

   Placebos have been shown to work in about 30 percent of patients, and
   they've been used by doctors for ages. In fact, they were often the
   only thing that a doctor could offer to relieve suffering, other than
   his or her attention and support. Some researchers believe that
   placebos simply evoke a psychological response. The act of taking them
   gives you an improved sense of well-being. However, recent research
   indicates that placebos may also bring about a physical response. In
   light of this, some people don't see anything wrong with a doctor
   prescribing a placebo. After all, he or she is doing it to help the
   patient. But others see the practice not only as harmful, but
   unethical, deceptive and possibly even illegal.

   Although we've long known that placebos can work, we've only recently
   started to figure out how and why. On the next page, we'll look at some
   theories behind the therapeutic effects of placebos.
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     Page

     1

   Introduction to How the Placebo Effect Works

     2

   Placebos: Is It All in Your Head?

     3

   Placebos in Research

     4

   Prescribing Placebos

     5

   The Placebo Prescribing Controversy

     6

   Lots More Information

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Placebo Effect

What is a placebo?

   A placebo (pluh-see-bow) is a substance or other kind of treatment that
   looks just like a regular treatment or medicine, but it’s not. It’s
   actually an inactive “look-alike” treatment or substance. This means
   it’s not a medicine. The person getting a placebo does not know for
   sure that the treatment is not real. Sometimes the placebo is in the
   form of a “sugar pill,” but a placebo can also be an injection, a
   liquid, or even a procedure. It’s designed to look like a real
   treatment, but doesn’t directly affect the illness.

What is the placebo effect?

   Even though they do not act on the disease, placebos seem to affect how
   people feel (this happens in up to 1 out of 3 patients). A change in a
   person’s symptoms as a result of getting a placebo is called the
   placebo effect. Usually the term “placebo effect” speaks to the helpful
   effects a placebo has in relieving symptoms. This effect usually lasts
   only a short time. It’s thought to have something to do with the body’s
   chemical ability to briefly relieve pain or certain other symptoms.

   But sometimes the effect goes the other way, and causes unpleasant
   symptoms or worse. These may include headaches, nervousness, nausea, or
   constipation, to name a few of the possible “side effects.” The
   unpleasant effects that happen after getting a placebo are sometimes
   called the nocebo effect.

   Together, these 2 types of outcomes are sometimes called expectation
   effects. This means that the person taking the placebo may experience
   something along the lines of what he or she expects to happen. If a
   person expects to feel better, that may happen. If the person believes
   that he or she is getting a strong medicine, the placebo may be thought
   to cause the side effects. The placebo does not cause any of these
   effects directly. Instead, the person’s belief in or experience of the
   placebo helps change the symptoms, or change the way the person
   perceives the symptoms.

   Some patients can have the placebo effect without getting a pill, shot,
   or procedure. Some may just feel better from visiting the doctor or
   doing something else they believe will help. That type of placebo
   effect seems most related to the degree of confidence and faith the
   patient has in the doctor or activity.

How are placebos used?

   Placebos may be used in clinical trials. Clinical trials are research
   studies testing new drugs or other treatments in volunteers. Before a
   new treatment is used on people, it’s studied in the lab. If lab
   studies suggest the treatment will work, the next step is to test it on
   animals. If that also gives promising results, it may then be tested in
   clinical trials to see if it has value for patients. The main questions
   the researchers want to answer are:
     * Does this treatment work?
     * Does it work better than what we’re now using?
     * What side effects does it cause?
     * Do the benefits of the treatment outweigh the risks?
     * Which patients are most likely to find this treatment helpful?

   If standard treatments for the disease are already available, the new
   treatment is usually compared to one of these treatments. This tells
   researchers if the new treatment is as good as or better than the one
   that’s currently available.

   If there’s no approved treatment for an illness or condition, some
   people in the study may be given a placebo, while others get the new
   treatment being tested. The main reason to have a placebo group is to
   be sure that any effects that happen are actually caused by the
   treatment and not some other factor.

   The placebo looks, tastes, or feels just like the actual treatment, so
   that the patient’s and the doctor’s expectations don’t affect the
   outcomes. The placebo control makes it possible to “blind” patients and
   doctors to what treatment they’re getting. In a double-blind controlled
   study, neither the volunteers taking part in the study nor their
   doctors know who’s getting which treatment. This study design helps
   avoid biases in measuring outcomes that can be caused by the
   researchers’ or the patients’ expectations about the treatment. This is
   not as big a problem in studies of cancer treatment, where objective
   outcome measures are most often used. It’s more likely in studies that
   require patient reporting for symptoms like depression, sleeplessness,
   or pain.

   If you would like to know more about clinical trials, see our document
   called Clinical Trials: What You Need to Know.

   People in a study that uses a placebo should always know that there’s a
   chance they could be getting a placebo. It’s not OK to give someone a
   treatment in a clinical trial and not mention that it could be a
   placebo. Please see our document Informed Consent for more information
   on this.

   Those who get placebos in medical studies serve an important role.
   Their responses help provide a good way to measure the actual effect of
   the treatment being tested. The placebo group provides an important
   baseline with which to compare the treatment group. It helps
   researchers see what would have happened without the treatment, though
   both groups may still have some short-term effects based on what the
   patient expects. For instance, illnesses that sometimes go away on
   their own might be thought to get better because of the medicine,
   unless there’s a placebo group and those people get better too. On the
   other side, bad effects that were going to happen anyway, or that occur
   from some unrelated cause, may be blamed on the treatment unless they
   also happen to people in the placebo group.

How does the placebo effect work?

   In the past, some researchers have questioned whether there’s
   convincing proof that the placebo effect is a real effect. But there
   are studies showing that the placebo effect is real. For example,
   scientists have recorded brain activity in response to placebo. Since
   many scientific tests have shown the placebo effect, it’s one way we
   know for sure that the mind and body are connected.

   Some scientific evidence suggests that the placebo effect may be partly
   due to the release of endorphins in the brain. Endorphins are the
   body’s natural pain killers. But there’s probably more to it than this.

   Many think the placebo effect occurs because the patient believes in
   the substance, the treatment, or the doctor. The patient’s thoughts and
   feelings somehow cause short-term physical changes in the brain or
   body. The patient expects to feel better, and so he or she does feel
   better for some time. But even if a person feels better after taking a
   placebo, it doesn’t mean the person’s illness or symptoms were not
   real. For instance, the person may feel less anxious, so stress
   hormones drop. Taking a placebo may change their perception — for
   example, a person might re-interpret a sharp pain as uncomfortable
   tingling.

   What’s commonly called the placebo effect even plays a role in
   mainstream medicine. Many people feel better after they get medical
   treatments that they expect to work. But the opposite can also happen,
   and this seems to support the idea of the expectation effect even more.
   For example, in one study, people with Alzheimer’s disease got less
   relief from pain medicines. These patients required higher doses —
   possibly because they had forgotten they were getting the drugs, or
   they forgot that the pain medicines had worked for them before.

   This suggests that past experiences also play into the placebo effect.
   In one study that looked at the placebo effect in pain relief, one
   group got a real pain medicine and the other did not. In the following
   days, both groups were given a placebo that looked like the real pain
   medicine. Those who had gotten the real pain medicine were able to
   tolerate more pain than those who had not gotten pain medicines before.

   In the same study, people who were given a drug that raised a certain
   hormone level beforehand actually had a similar (but smaller) hormone
   response when they were given a placebo later. Those who had not gotten
   the real drug beforehand had no change in their hormone levels when
   they got the placebo, even though they were told that they would. This
   helped to separate the power of the researcher telling them they would
   have an effect from the learned experience of having the effect in the
   past. This type of learned response after personal experience is called
   the conditioning effect. It seems to be part of what we call the
   placebo effect.

   The nocebo effect, in which a person has more symptoms or side effects
   after a placebo, is still being studied. Researchers believe it may be
   partly explained by a substance in the body that sends messages through
   the nerves. When a person is anxious, for instance, the substance is
   activated and the person feels more pain than a person who isn’t
   anxious. The nocebo effect shows up in the brain: brain-imaging studies
   have shown that pain is more intense when a person expects more pain
   than when they don’t. This is linked to changes in certain brain
   regions on the imaging studies.

   Although we may not know exactly how it works, the idea that the mind
   can affect the body has been around for thousands of years and is
   well-proven in certain situations. Many ancient cultures depended on
   mind-body connections to treat illness. Shamans or medicine men would
   not have viewed their efforts as placebos. But their healing powers may
   have worked partly through the patient’s strong belief that the
   shaman’s treatments would restore health. Or it could be that a sick
   person was going to get better anyway, but the recovery was thought to
   be because of the treatment — which might have really done nothing for
   the illness.

   Because placebos often have an effect, even if the effect doesn’t last
   long, some people think that the placebo produced a cure. But placebos
   do not cure. And in studies where doctors are looking at whether a
   tumor shrinks, placebos have very little, if any, effect.

   Still, placebos clearly can help reduce certain symptoms such as pain,
   anxiety, and trouble sleeping in some people. In earlier times,
   placebos were sometimes given by doctors out of frustration or
   desperation, because nothing else was available or seemed to work. They
   might even be tried today — a 2008 study found that nearly half of the
   doctors polled said that they used a placebo when they felt that it
   might help the patient feel better.

   Sometimes if the placebo looks more real, the person may think it’s an
   active medicine or treatment and believe in its power even more. For
   example, a larger pill may look more powerful than a small pill. And in
   some people, an injection may have a stronger placebo effect than a
   pill.

   Some believe that placebos seem to work because many illnesses improve
   over time even without treatment. People may also take better care of
   themselves by exercising, eating healthier, or resting if they are
   taking a placebo. Just as natural endorphins may relieve pain once they
   are released, some research shows the brain may respond to an imagined
   scene much as it would to something it actually sees. A placebo may
   help the brain remember a time before the symptoms and bring about a
   chemical change. This is a theory called remembered wellness.

   Some scientists believe that the effects of many alternative therapies
   may simply be a placebo effect. If the patient believes in the
   treatment and wants it to work, it can seem to do so, at least for a
   while. If this effect worked on an illness that usually would not get
   better on its own, and it lasted, it would be considered a real cure,
   not a placebo effect.

   Finally, there’s evidence to suggest that what a patient expects about
   real medicines can influence how the patient feels after the medicine
   is taken. Even though responses from real drugs aren’t typically
   thought of as placebo effects, some short-term effects are affected by
   expectations — good ones as well as bad.

   There’s still much to find out about the placebo effect and all the
   ways it may work. Researchers agree that the placebo effect cannot cure
   people or make them live substantially longer. Still, they continue to
   study it in order to learn more about it, and find out whether and how
   it may be used to help people feel better.

Other things that can add to or be confused for the placebo effect

   Certain other factors can affect study outcomes, and may be confused
   with the placebo effect. These are effects that can cause a study to
   report that a placebo (or even a treatment) had some effect when in
   reality, it didn’t.

Timing of unrelated events

   Along with the placebo or nocebo effect, incidental events (unrelated
   effects that might have happened without the placebo) might also be
   linked to the placebo because of their timing. For example, a headache
   or rash that happens soon after taking a placebo could be caused by
   something else entirely, but the person might think the placebo caused
   it. The same can be said for good outcomes: if a person happened to
   start feeling better after taking a placebo, that improvement may be
   thought to be due to the placebo.

   Healing or changes in symptoms

   A health problem that improves on its own (many do) can sometimes add
   to what’s thought of as the placebo effect. Even in serious conditions
   such as cancer, some types appear to get better and worse on their own,
   although they continue to spread and worsen over time. This is part of
   the effect of timing, noted above. A person who was taking a placebo
   when symptoms started improving on their own is very likely to believe
   that the placebo had some effect. And a self-limited illness that goes
   away completely on its own at such a time might have the placebo-taker
   convinced it was a miracle drug.

Patient reporting

   Lack of blinding can affect reporting of these kinds of coincidental
   timing effects and belief in what caused them. For example, people who
   know they’re getting placebos will know that their headache is not due
   to the medicine, and may not report it. Those who know they are getting
   the real medicine are more likely to believe that the medicine is
   causing the headache, and are more likely to report it. Blinding helps
   to balance these incidental timing effects.

Self-report of symptoms on a scale

   Studies comparing placebo to no treatment found that patients were more
   likely to tell the study investigator that there was some improvement
   in their comfort if they were on placebo. This was observed when the
   patient had to rank their symptoms on a scale, say, from 1 to 10. When
   the patients’ rankings were compared with outcomes others could measure
   (signs, like swelling or movement) there would be no improvement in the
   measurable outcome. Some researchers believe this is due to patients
   wanting to give the investigator good news. It may also be that the
   patient is comparing current symptoms to the worst discomfort this
   problem had caused in the past.

Getting outside treatment

   The patient who isn’t getting better in a study may also seek outside
   medical help without mentioning it to investigators. Or outside
   treatment for a related problem may help the symptom being studied in
   the clinical trial. This can affect outcomes for both the placebo and
   treatment groups.

Study dropouts

   People who are not getting better in the study, including those on
   placebo, are more likely to leave the study before it’s over. This
   means that people who aren’t helped are less likely to be counted in
   the final analysis. This makes any treatment look as if it works better
   than it does, because the people who felt better during treatment were
   more likely to have their results counted at the end of the study than
   those who didn’t.

To learn more

More information from your American Cancer Society

   Here is more information you might find helpful. You also can order
   free copies of our documents from our toll-free number, 1-800-227-2345,
   or read them on our Web site, www.cancer.org.

   Clinical Trials: What You Need to Know (also in Spanish)

   Complementary and Alternative Methods for Cancer Management (also in
   Spanish)

   Dietary Supplements: How to Know What Is Safe

   Guidelines for Using Complementary and Alternative Methods

   Learning About New Cancer Treatments

   Informed Consent (also in Spanish)

   American Cancer Society Operational Statement on Complementary and
   Alternative Methods of Cancer Management

   Along with the above, information on many different types of cancer
   treatment, including complementary and alternative treatments, are
   available at no cost to you from the American Cancer Society. You can
   find them on our Web site or request a copy from our toll-free number
   as noted above.

Other organizations and Web sites*

   Today there’s a great deal of interest in complementary and alternative
   therapies. Mass communication, especially the Internet, makes it
   possible for people to share ideas and information very quickly. But
   too often information on the Internet is written by promoters of
   useless treatments. Along with the American Cancer Society, the
   following is a partial list of Web sites and phone numbers of reputable
   groups that provide information on complementary and alternative
   therapies, and in some cases, other cancer information:

   National Cancer Institute
   Web site: www.cancer.gov
   Toll-free number: 1-800-422-6237 (1-800-4-CANCER)
   TTY: 1-800-332-8615
   Offers information about cancer, treatment, clinical trials, and
       related help on many cancer topics

   National Center for Complementary and Alternative Medicine (NCCAM)
   Web site: http://nccam.nih.gov
   Toll-free number: 1-888-644-6226
   TTY: 1-866-464-3615
   Offers more details on many complementary treatments

   Memorial Sloan Kettering Cancer Center
   About Herbs and Botanicals
   Web site:
   www.mskcc.org/cancer-care/integrative-medicine/about-herbs-botanicals-o
   ther-products
   Has summaries of information on a number of complementary and
       alternative treatments

   MD Anderson Complementary/Integrative Medicine Education Resources
   (CIMER)
   Web site:
   www.mdanderson.org/education-and-research/resources-for-professionals/c
   linical-tools-and-resources/cimer/therapies/index.html

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   Center
   Web site: http://fnic.nal.usda.gov
   Choose “Dietary Supplements” from the left menu bar for information on
       dietary supplements, including vitamins and minerals

   United States Food and Drug Administration
   Web site: www.fda.gov/Food/DietarySupplements/default.htm
   Toll-free number: 1-888-463-6332 (1-888-INFO-FDA)
   Has information on dietary and food supplements. You can also report
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   Web Site: www.ncahf.org
   To help you discern scammers and fraudsters from real cancer treatment

   Quackwatch
   Web Site: www.quackwatch.org
   Reports on so-called cancer treatments that don’t actually work

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   No matter who you are, we can help. Contact us anytime, day or night,
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   www.cancer.org.

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   Hróbjartsson A, Gøtzsche PC. Is the placebo powerless? An analysis of
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   Sherman R, Hickner J. Academic physicians use placebos in clinical
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   Features

The Placebo Phenomenon


   An ingenious researcher finds the real ingredients of “fake” medicine.
   Research
     * Photograph by Jim HarrisonTed Kaptchuk in his home office in
       Cambridge

   Print | PDF | Reprints
   by Cara Feinberg
   January-February 2013
   Email

Keywords

   Harvard Medical School, health and medicine, placebos, Ted Kaptchuk

   Two weeks into Ted Kaptchuk’s first randomized clinical drug trial,
   nearly a third of his 270 subjects complained of awful side effects.
   All the patients had joined the study hoping to alleviate severe arm
   pain: carpal tunnel, tendinitis, chronic pain in the elbow, shoulder,
   wrist. In one part of the study, half the subjects received
   pain-reducing pills; the others were offered acupuncture treatments.
   And in both cases, people began to call in, saying they couldn’t get
   out of bed. The pills were making them sluggish, the needles caused
   swelling and redness; some patients’ pain ballooned to nightmarish
   levels. “The side effects were simply amazing,” Kaptchuk explains;
   curiously, they were exactly what patients had been warned their
   treatment might produce. But even more astounding, most of the other
   patients reported real relief, and those who received acupuncture felt
   even better than those on the anti-pain pill. These were exceptional
   findings: no one had ever proven that acupuncture worked better than
   painkillers. But Kaptchuk’s study didn’t prove it, either. The pills
   his team had given patients were actually made of cornstarch; the
   “acupuncture” needles were retractable shams that never pierced the
   skin. The study wasn’t aimed at comparing two treatments. It was
   designed to compare two fakes.

   Although Kaptchuk, an associate professor of medicine, has spent his
   career studying these mysterious human reactions, he doesn’t argue that
   you can simply “think yourself better.” “Sham treatment won’t shrink
   tumors or cure viruses,” he says.

   But researchers have found that placebo treatments—interventions with
   no active drug ingredients—can stimulate real physiological responses,
   from changes in heart rate and blood pressure to chemical activity in
   the brain, in cases involving pain, depression, anxiety, fatigue, and
   even some symptoms of Parkinson’s.

   The challenge now, says Kaptchuk, is to uncover the mechanisms behind
   these physiological responses—what is happening in our bodies, in our
   brains, in the method of placebo delivery (pill or needle, for
   example), even in the room where placebo treatments are administered
   (are the physical surroundings calming? is the doctor caring or curt?).
   The placebo effect is actually many effects woven together—some
   stronger than others—and that’s what Kaptchuk hopes his “pill versus
   needle” study shows. The experiment, among the first to tease apart the
   components of placebo response, shows that the methods of placebo
   administration are as important as the administration itself, he
   explains. It’s valuable insight for any caregiver: patients’
   perceptions matter, and the ways physicians frame perceptions can have
   significant effects on their patients’ health.

   For the last 15 years, Kaptchuk and fellow researchers have been
   dissecting placebo interventions—treatments that, prior to the 1990s,
   had been studied largely as foils to “real” drugs. To prove amedicine
   is effective, pharmaceutical companies must show not only that their
   drug has the desired effects, but that the effects are significantly
   greater than those of a placebo control group. Both groups often show
   healing results, Kaptchuk explains, yet for years, “We were struggling
   to increase drug effects while no one was trying to increase the
   placebo effect.”

   Last year, he and colleagues from several Harvard-affiliated hospitals
   created the Program in Placebo Studies and the Therapeutic Encounter
   (PiPS), headquartered at Beth Israel Deaconess Medical Center—the only
   multidisciplinary institute dedicated solely to placebo study. It’s a
   nod to changing attitudes in Western medicine, and a direct result of
   the small but growing group of researchers like Kaptchuk who study not
   if, but how, placebo effects work. Explanations for the phenomenon come
   from fields across the scientific map—clinical science, psychology,
   anthropology, biology, social economics, neuroscience. Disregarding the
   knowledge that placebo treatments can affect certain ailments, Kaptchuk
   says, “is like ignoring a huge chunk of healthcare.” As caregivers, “we
   should be using every tool in the box.”

   Western medicine, however, has been slow to agree with him—partly
   because of his message, and in his case, often because of the
   messenger. An acupuncturist by training, he is an unlikely leader in
   the halls of academia. With a degree in Chinese medicine from an
   institute in Macao, Kaptchuk is one of the few faculty members at
   Harvard Medical School (HMS) with neither a Ph.D. nor M.D.—“a debit,
   not a credit at most medical schools,” says Finland professor of
   clinical pharmacology emeritus Peter Goldman, one of his early Harvard
   advisers. (Kaptchuk’s diploma is recognized as a doctorate in many
   states, but not in Massachusetts.) When Kaptchuk came to Harvard in
   1995, “he knew about Chinese herbs and healing needles, and he’d
   written a very fine book on Chinese medicine [The Web That Has No
   Weaver (1983)],” says Goldman, “but he didn’t know the first thing
   about how to conduct clinical studies.”

   Kaptchuk joined the faculty as an instructor in medicine and
   apprenticed himself to several seasoned clinicians and investigators.
   Within a few years, he was winning National Institutes of Health grants
   and publishing in medicine’s top journals. “What his colleagues saw was
   a fierce intellect and curiosity,” said Goldman. “He was asking
   questions no one was asking.”

   Ironically, says Kaptchuk, it was his success as an acupuncturist that
   made him leave the profession for academia. “Patients who came to me
   got better,” he says, but sometimes their relief began even before he’d
   started his treatments. He didn’t doubt the value of acupuncture, but
   he suspected something else was at work. His hunch was that it was his
   engagement with patients—and perhaps even the act of caring itself.

   For his ideas to gain traction with Western doctors, however, Kaptchuk
   knew he needed scientific proof. His chance would come in the early
   2000s in a collaboration with gastroenterologists studying irritable
   bowel syndrome (IBS), a chronic gastrointestinal disorder accompanied
   by pain and constipation. The experiment split 262 adults with IBS into
   three groups: a no-treatment control group, told they were on a waiting
   list for treatment; a second group who received sham acupuncture
   without much interaction with the practitioner; and a third group who
   received sham acupuncture with great attention lavished upon them—at
   least 20 minutes of what Kaptchuk describes as “very schmaltzy” care
   (“I’m so glad to meet you”; “I know how difficult this is for you”;
   “This treatment has excellent results”). Practitioners were also
   required to touch the hands or shoulders of members of the third group
   and spend at least 20 seconds lost in thoughtful silence.

   The results were not surprising: the patients who experienced the
   greatest relief were those who received the most care. But in an age of
   rushed doctor’s visits and packed waiting rooms, it was the first study
   to show a “dose-dependent response” for a placebo: the more care people
   got—even if it was fake—the better they tended to fare.

   Kaptchuk’s innovative studies were among the first to separate
   components of the placebo effect, explains Applebaum professor of
   medicine Russell Phillips, director of the Center for Primary Care at
   HMS. For years, doctor-patient interactions were lumped into a generic
   “placebo response”: a sum of such variables as patients’ reporting bias
   (a conscious or unconscious desire to please the researchers); patients
   simply responding to doctors’ attention; the different methods of
   placebo delivery; and symptoms subsiding without treatment—the
   inevitable trajectory of most chronic ailments. “There was simply no
   way to quantify the ritual of medicine,” says Phillips of the
   doctor-patient interaction. And the ritual, he adds, is the one finding
   from placebo research that doctors can apply to their practice
   immediately.

   But other placebo treatments (sham acupuncture, pills, or other fake
   interventions) are nowhere near ready for clinical application—and
   Kaptchuk is not recommending that they should be. Such treatments all
   require deception on the part of doctors, an aspect of placebo medicine
   that raises serious ethical questions for practitioners.

   This was disturbing for Kaptchuk, too; deception played no role in his
   own success as a healer. But years of considering the question led him
   to his next clinical experiment: What if he simply told people they
   were taking placebos? The question ultimately inspired a pilot study,
   published by the peer-reviewed science and medicine journal PLOS ONE in
   2010, that yielded his most famous findings to date. His team again
   compared two groups of IBS sufferers. One group received no treatment.
   The other patients were told they’d be taking fake, inert drugs
   (delivered in bottles labeled “placebo pills”) and told also that
   placebos often have healing effects.

   The study’s results shocked the investigators themselves: even patients
   who knew they were taking placebos described real improvement,
   reporting twice as much symptom relief as the no-treatment group.
   That’s a difference so significant, says Kaptchuk, it’s comparable to
   the improvement seen in trials for the best real IBS drugs.

   Although this IBS “open-label” study was small and has yet to be
   replicated, fellow placebo researcher Frank Miller of the department of
   bioethics at the National Institutes of Health considers it a
   significant step toward legitimizing placebo studies. But to really
   change minds in mainstream medicine, Miller says, researchers have to
   show biological evidence that minds actually change—a feat achieved
   only in the last decade through imaging technology such as positron
   emission tomography (PET) scans and functional magnetic resonance
   imaging (fMRI).

   The first evidence of a physiological basis for the placebo effect
   appeared in the late 1970s, when researchers studying dental patients
   found that by chemically blocking the release of endorphins—the brain’s
   natural pain relievers—scientists could also block the placebo effect.
   This suggested that placebo treatments spurred chemical responses in
   the brain that are similar to those of active drugs, a theory borne out
   two decades later by brain-scan technology. Researchers like
   neuroscientist Fabrizio Benedetti at the University of Turin have since
   shown that many neurotransmitters are at work—including chemicals that
   use the same pathways as opium and marijuana. Studies by other
   researchers have shown that placebos increase dopamine (a chemical that
   affects emotions and sensations of pleasure and reward) in the brains
   of Parkinson’s patients, and patients suffering from depression who’ve
   been given placebos reveal changes in electrical and metabolic activity
   in several different regions of the brain.

   Kaptchuk’s team has investigated the neural mechanisms of placebos in
   collaboration with the Martinos Center for Biomedical Imaging at
   Massachusetts General Hospital. In two fMRI studies published in the
   Journal of Neuroscience in 2006 and 2008, they showed that placebo
   treatments affect the areas of the brain that modulate pain reception,
   as do negative side effects from placebo treatment—“nocebo effects.”
   (Nocebo is Latin for “I shall harm”; placebo means “I shall please.”)
   But nocebo effects also activate the hippocampus, a different area
   associated with memory and anxiety. As happened with Kaptchuk’s
   patients in the “pill versus needle” study, the headaches, nausea,
   insomnia, and fatigue that result from fake treatments can be painfully
   real, afflicting about a quarter of those assigned to placebo treatment
   in drug trials(see “The Nocebo Effect,” May-June 2005). “What we
   ‘placebo neuroscientists’…have learned [is] that therapeutic rituals
   move a lot of molecules in the patients’ brain, and these molecules are
   the very same as those activated by the drugs we give in routine
   clinical practice,” Benedetti wrote in an e-mail. “In other words,
   rituals and drugs use the very same biochemical pathways to influence
   the patient’s brain.” It’s those advances in “hard science,” he added,
   that have given placebo research a legitimacy it never enjoyed before.

   This new visibility has encouraged not only research funds but also
   interest from healthcare organizations and pharmaceutical companies. As
   healthcare companies increasingly reward doctors for maintaining
   patients’ health (rather than for the number of procedures they
   perform), “research like Ted’s becomes increasingly relevant,” says
   Minot professor of medicine and HMS dean for graduate education David
   Golan, a professor of biological chemistry and molecular pharmacology.

   This year, the Robert Wood Johnson Foundation, the nation’s largest
   philanthropy focused on health and healthcare, awarded Kaptchuk’s PiPS
   program a $250,000 grant to support a series of seminars at Harvard
   designed to connect placebo experts with researchers in related fields.
   And the latest findings to emerge from PiPS—a 2012 study showing that
   genetic variations may explain why only certain people respond to
   placebo effects—has caught the attention of the Food and Drug
   Administration.

   That study, published last Octoberin PLOS ONE, showed that patients
   with a certain variation of a gene linked to the release of dopamine
   were more likely to respond to sham acupuncture than patients with a
   different variation—findings that could change the way pharmaceutical
   companies conduct drug trials, says Gunther Winkler, principal of ASPB
   Consulting, LLC, which advises biotech and pharmaceutical firms.
   Companies spend millions of dollars and often decades testing drugs;
   every drug must outperform placebos if it is to be marketed. “If we can
   identify people who have a low predisposition for placebo response,
   drug companies can preselect for them,” says Winkler. “This could
   seriously reduce the size, cost, and duration of clinical
   trials…bringing cheaper drugs to the market years earlier than before.”

   Not all of Kaptchuk’s studies have been so warmly received. Though few
   academics quarrel with the quality of his research, he’s remained a
   prime target for such watchdog groups as Quackwatch and The Skeptics’
   Society, organizations that question nonconventional medical
   approaches. (Other well-known targets include Deepak Chopra, Andrew
   Weil ’63, M.D. ’68, and the late Nobel Prize winner Linus Pauling.) In
   2011, he and a team of researchers published a paper in The New England
   Journal of Medicine (NEJM) that raised the hackles of some of his
   fiercest critics.

   That paper (praised by scholars as one of the most carefully controlled
   and definitive placebo studies ever done) described a study of 40
   asthma patients given four different interventions: active treatments
   with real albuterol inhalers; placebo treatments with fake inhalers
   that delivered no medication; sham acupuncture treatments; and
   intervals with no treatment at all. The patients returned for 12
   sequential visits, receiving each type of treatment three times—a novel
   approach in placebo study that created a large amount of data (480
   treatments in total) and turned subjects into their own controls (if
   patients are compared to themselves from one treatment to the next,
   researchers can eliminate subjects’ individual differences as a
   variable). The researchers had hoped to find improved lung function
   with both the real and sham treatments; what they found instead was
   that only the real treatment yielded results—the others showed no
   significant improvement. Yet when Kaptchuk’s team measured patients’
   own assessments of improvement, the researchers found no difference
   reported between the real and sham treatments: the patients’subjective
   responses directly contradicted their own objective physical measures.

   To Dr. Harriet Hall, a retired family physician who writes critically
   about alternative and complementary medicine for such publications as
   Skeptic Magazine and Skeptical Inquirer, this discrepancy between
   objective and subjective results is precisely where the danger lies. As
   she told a reporter for The Atlantic in December 2011, following the
   publication of Kaptchuk’s NEJM study, “Asthma can be fatal. If the
   patient’s lung function is getting worse but a placebo makes them feel
   better, they might delay treatment until it is too late.”

   To Kaptchuk’s team, on the other hand, the conflicting results not only
   reveal important lessons for researchers and clinicians, but illuminate
   a gap that is central to placebo research. “Placebos have limitations,
   and we need to know what they are,” Kaptchuk says. “We’d hoped for
   measurable objective changes in breathing; what we got instead was a
   more precise diagram of placebo effects and how clearly the ritual of
   medicine makes people more comfortable.” That in itself is important
   information, he says. “Our job is to make people feel better,” and
   though this study was small, “what we’ve really done here is open up a
   new set of questions.” No one has yet studied how long-term experience
   with the ritual of medicine might ultimately affect the course of
   chronic afflictions, he says. “We hope we’ve opened up that path.”

   Kaptchuk and his team have begun to take steps in that direction,
   continuing to ask new questions and push the boundaries of placebo
   research. A study published online this past year in the Proceedings of
   the National Academy of Sciences demonstrated that the placebo response
   can occur even at the unconscious level. The team showed that images
   flashed on a screen for a fraction of a second—too quickly for
   conscious recognition—could trigger the response,but only if patients
   had learned earlier to associate those specific images with healing.
   Thus, when patients enter a room containing medical equipment they
   associate with the possibility of feeling better, “the mind may
   automatically make associations that lead to actual positive health
   outcomes,” says psychiatry research fellow Karin Jensen, the study’s
   lead author.

   Those findings led to the team’s most recent work: imaging the brains
   of physicians whilethey treat patients—a side of the treatment equation
   that no one had previously examined. (The researchers constructed an
   elaborate set-up in which the doctors lay in fMRI machines specially
   equipped to enable them both to see their patients outside the machine
   and administer what they thought was a nerve-stimulating treatment.)
   “Doctors give subtle cues to their patients that neither may be aware
   of,” Kaptchuk explains. “They are a key ingredient in the ritual of
   medicine.” The hope is that the new brain scans will reveal how
   doctors’ unconscious thought figures into the treatment recipe.

   Within academia, Kaptchuk and his fellow researchers have not escaped
   criticism, but the voices have been few and far between. The most
   notable appeared in 2001 in the NEJM—the same publication that included
   Kaptchuk’s asthma study a decade later. In a paper titled, “Is the
   Placebo Powerless?” two Danish researchers reviewed 114 published
   studies involving 7,500 patients and questioned both the research
   methods and the short duration of most placebo studies. Many of the
   trials reviewed lacked “no-treatment” groups—an important control group
   missing even in Kaptchuk’s first “pill versus needle” study.

   But Kaptchuk’s response to such criticism is perhaps as rare in
   academia as his pedigree. “If I remember correctly,” said Asbjorn
   Hrobjartsson, the lead author of that 2001 paper during a recent phone
   conversation, “Ted was already thinking along the same lines as we were
   and realized [our paper] pointed out real methodological problems.”
   When Hrobjartsson came to speak at Harvard a year later, he stayed at
   Kaptchuk’s home, and in 2011, the two coauthored a paper (with the
   NIH’s Frank Miller) on biases and best practices in placebo study.

   When Kaptchuk talks about Hrobjartsson’s 2001 paper now, he winces,
   then nods with acceptance. “At first when I read it, I worried I’d be
   out of a job,” he says. “But frankly, [Hrobjartsson] was absolutely
   right.” In order to legitimize his findings to mainstream
   practitioners, the results must be expertly quantified, he
   acknowledges. “We have to transform the art of medicine into the
   science of care.”

   Cara Feinberg is a journalist working in print and documentary
   television. She can be reached through her website at
   www.CaraFeinberg.com.
   View the discussion thread.

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   home > medterms medical dictionary a-z list > placebo effect definition
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   Definition of Placebo effect

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      Placebo effect: Also called the placebo response. A remarkable
      phenomenon in which a placebo -- a fake treatment, an inactive
      substance like sugar, distilled water, or saline solution -- can
      sometimes improve a patient's condition simply because the person has
      the expectation that it will be helpful. Expectation to plays a potent
      role in the placebo effect. The more a person believes they are going
      to benefit from a treatment, the more likely it is that they will
      experience a benefit.

      To separate out this power of positive thinking and some other
      variables from a drug's true medical benefits, companies seeking
      governmental approval of a new treatment often use placebo-controlled
      drug studies. If patients on the new drug fare significantly better
      than those taking placebo, the study helps support the conclusion that
      the medicine is effective.

      The power of positive thinking is not a new subject. The Talmud, the
      ancient compendium of rabbinical thought, states that: "Where there is
      hope, there is life." And hope is positive expectation, by another
      name. The scientific study of the placebo effect is usually dated to
      the pioneering paper published in 1955 on "The Powerful Placebo" by the
      anesthesiologist Henry K. Beecher (1904-1976). Beecher concluded that,
      across the 26 studies he analyzed, an average of 32% of patients
      responded to placebo.

      It has been shown that placebos have measurable physiological effects.
      They tend to speed up pulse rate, increase blood pressure, and improve
      reaction speeds, for example, when participants are told they have
      taken a stimulant. Placebos have the opposite physiological effects
      when participants are told they have taken a sleep-producing drug.

      The placebo effect is part of the human potential to react positively
      to a healer. A patient's distress may be relieved by something for
      which there is no medical basis. A familiar example is Band-Aid put on
      a child. It can make the child feel better by its soothing effect,
      though there is no medical reason it should make the child feel better.

      People who receive a placebo may also experience negative effects. They
      are like side effects with a medication and may include, for example,
      nausea, diarrhea and constipation. A negative placebo effect has been
      called the nocebo effect.
      Last Editorial Review: 6/14/2012


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Bronze-level article Placebo effect

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   v - t - e
   “”No one doubts—certainly not I—that the mind exercises a powerful
   influence over the body. From the beginning of time, the sorcerer, the
   interpreter of dreams, the fortune-teller, the charlatan, the quack,
   the wild medicine-man, the educated physician, the mesmerist, and the
   hypnotist have made use of the client's imagination to help them in
   their work. They have all recognized the potency and availability of
   that force. Physicians cure many patients with a bread pill; they know
   that where the disease is only a fancy, the patient's confidence in the
   doctor will make the bread pill effective.
   —Mark Twain, Christian Science, 1907.

   The placebo effect is a psychosomatic phenomenon in which symptoms of a
   disease or condition lessen — or even appear to be cured completely —
   from the patient being merely exposed to a treatment. Believing that
   their condition will be improved, they will begin to feel better and
   perhaps identifiable symptoms may disappear, irrespective of whether
   the treatment has any chemical or pharmacological effect. Because of
   this, controlling for the placebo effect is an essential part of
   medicine. For example, sugar pills or saline solutions, which have no
   pharmacological properties, are commonly prescribed as placebo
   treatments to control for the effect the simple act of intervening in a
   patient's illness may have.

   Most alternative medicine is suggested to work through this method^[1]
   — mostly because any treatment that doesn't work through this method is
   labelled "medicine". Under placebo control, alternative medicines do
   not perform significantly better.

   Contents

        * 1 Causes
             + 1.1 Statistical vs individual experience
             + 1.2 Expectation effects
        * 2 Ethical considerations
        * 3 Use in medical trials
        * 4 The strangeness of the placebo effect
        * 5 Nocebo effect
        * 6 False placebo
        * 7 See also
        * 8 Footnotes

[edit] Causes

[edit] Statistical vs individual experience

   The placebo effect is quite a complex phenomenon. It is influenced by a
   multitude of things, including positive thought, reduced stress, the
   intensity or "drama" of the medical intervention, a patient's
   expectations of what the treatment can do, and the wider cultural
   meaning of medical treatment. A particularly interesting observation is
   how much these factors can be influenced subconsciously; a doctor
   merely telling someone a treatment will work may not produce such a
   dramatic effect if the doctor doesn't actually believe it too. Because
   of the complexity of issues surrounding what causes a sick patient to
   get "better", it's difficult to say if an individual was cured by a
   placebo effect, real treatment, regression to the mean or a complicated
   combination of all three. So, the placebo effect is best described as a
   statistical phenomenon, where prognosis improves for a certain
   percentage of patients simply exposed to a treatment of some kind.

   However, as the placebo effect is powered by belief in a treatment and
   exposure to it it can manifest in individuals to a certain extent. A
   homeopathic prescription of water containing a minute dilution of
   powdered oyster shell may bring some improvement to a patient who has
   total faith in the homeopathic method. A patient who is skeptical of
   homeopathy may experience a reduced effect or no effect at all, as
   demonstrated by James Randi when he regularly consumes massive
   overdoses of homeopathic sleeping pills on stage. If these two
   hypothetical patients begin to feel better anyway, the former would be
   likely to attribute it to the treatment while the latter would be
   likely to dismiss it as just feeling better anyway. This leads to
   selective reporting, and is why anecdotal evidence shouldn't be trusted
   over statistical data.

[edit] Expectation effects

   Expectations of what drugs and medical treatments can, and do, change
   over time. Often the efficacy of real drugs decreases when a new
   version is released, as people expect the new one to be better. New
   treatments, which are perceived to be more effective because they
   exploit new technologies induce a placebo effect in addition to their
   real effect and, sometimes, this can lead to an over-estimate of their
   real efficacy over an existing treatment. This is why in controlled
   studies of new treatments, they are compared not with inactive placebos
   but the best effective treatment available (and not least because it is
   unethical to use placebopathy where a working treatment is known) and
   the experience between patients is minimised so that they genuinely
   cannot tell the difference between treatment A and treatment B.

   It is an observed phenomenon that placebo drugs distributed in flashier
   packaging tend to produce a stronger reaction than their plain
   packaging counterparts.^[2] There is also evidence that the placebo
   effect can work even if the person knows that it is a placebo, as
   observed in a study of patients with irritable bowel syndrome.^[3]
   However, the statement issued to patients read "placebo pills made of
   an inert substance, like sugar pills, that have been shown in clinical
   studies to produce significant improvement in IBS symptoms through
   mind-body self-healing processes" - which still creates an expectation
   of treatment despite being told there was no chemical reason that such
   treatment would help.

   In short, the placebo effect works if you expect the placebo effect to
   work.

[edit] Ethical considerations

   There are a number of ethical issues surrounding the wilful use of
   placebos as a treatment - known as placebopathy. Many casual complaints
   can be dealt with by inactive placebo treatments (involving a sugar
   pill and a reassuring visit to a doctor) and this would save a
   significant amount of time, money and lowers the risk of drug
   dependency and overdose. Yet, despite these potential benefits to
   willingly issuing placebos, it is not considered ethical in modern
   medicine. Firstly, placebopathy involves medical professions deceiving
   their patients, which is considered bad ethical practice, and secondly
   there is a risk in delaying the treatment of a real condition due to a
   doctor mistrusting or underestimating their patient's symptoms. If a
   patient complaining of a headache is given a sugar pill to placate it,
   and it turns out to be a serious condition that requires treatment then
   at the very least this would be a serious law suit waiting to happen.

   Conversely, some medications that have been prescribed have later
   turned out to be no more effective than inactive placebos, yet can be
   an effective treatment for psychosomatic conditions or short-term
   illnesses. Because any treatment tends to produce a better effect than
   no treatment at all (hence the need for placebo control in trials, see
   below) it could be considered unethical to stop this practice of
   effective placebopathy.

[edit] Use in medical trials

   Oscillococcinum, a well-known homeopathic remedy that "works" by the
   placebo effect.

   Because the placebo effect is so powerful, efficacy claims for medical
   treatments must be tested in an experiment that controls for this
   effect. This is usually achieved by running a double-blind test, where
   some patients receive the treatment being examined, and others get a
   placebo. Neither the patients or the administrators of the treatment
   know who is in which group. In order for the treatment to be proved
   useful, it must produce results that are better than the placebo at a
   statistically significant level. In practice the "placebo" is usually
   an existing treatment, as being better than an placebo isn't enough - a
   new treatment has to be better than the existing one! For example, in
   trials of keyhole surgery over conventional open heart surgery,
   elaborate schemes were undertaken to make patients all feel as if they
   had the same treatment - but all were treated for their condition, none
   received a full "fake" treatment that did nothing. Similarly, new pills
   would be compared with the existing treatments they aim to replace, not
   necessarily sugar pills or more "powerful" (but more restricted) drugs.

   Placebo treatments can often be quite difficult to design, but are
   still possible. As mentioned above, placebo surgeries have been
   performed using quite elaborate theatre, and often the precise wording
   that a doctor must use to describe a treatment to a patient is strictly
   controlled. Such treatments can be used to test not just efficacy, but
   the explanations offered by alternative medicine practitioners. A
   placebo treatment to test acupuncture, for example, could be designed
   to test claims about meridian lines would involve sticking the needles
   into a patient but in more randomised areas rather than the specific
   places the technique claims are "special". A second placebo treatment
   could test the effect of needles by changing the depth which they
   penetrate into the skin - acupuncture needles often go deeper than you
   think, while placebo needles penetrate only the top layer of the skin.
   Thirdly the effect of a visit to a practitioner can be controlled for
   by using entirely "sham" needles which prick the skin, causing
   indistinguishable pain sensations, but otherwise don't penetrate or
   cause any lasting effect. These three methods combine to test three
   separate areas whereby an alternative medicine can work.

   Quacks who push woo treatments rely on the placebo effect when arguing
   that their "cures" have an effect. This is exactly why medical tests
   need to pit a drug against a placebo: anything will usually perform
   better than nothing. Often, proponents of alternative medicine will
   reject placebo controlled experiments for any number of excuses. For
   example, many homopathic practitioners assert that treatments must be
   assigned individually and so are unsuited to the format of a randomised
   controlled trial. Yet, such things can be overcome by simply exposing
   the patient to everything about the treatment, including this
   individual treatment "design", and simply swapping the medication at
   the last moment, unknown to both the patient and practitioner. This
   sort of assertion is common in alternative medicine, but is obviously
   at odds with the mass-produced remedies that are sold to the public.
   Such trials have been done (very rarely does the alternative medicine
   world foot the bill for these), and they invariably come up negative.

[edit] The strangeness of the placebo effect

   The power of the placebo effect produces many strange and interesting
   quirks. These indicate that the placebo effect may well be more than
   mere "mind over matter", and stem from what is known as a complex
   intervention. This is where any given treatment consists of not just
   the medicine issued, but the bedside manner of the doctor, how the
   treatment is described and sold, and how society and environment shape
   our expectations of what a treatment can and cannot do. Many of these
   examples and their ramifications are discussed in slightly more detail
   in Ben Goldacre's book Bad Science.
     * The effect has been observed in animals and babies. However, in
       practice this requires conditioning first, which is analogous to
       just telling someone a treatment will work when you can't
       communicate more directly.^[4]^[5] This is contrary to claims by
       homeopaths who claim that their remedies work in babies and animals
       and so cannot be due to the placebo effect. (Homeopathic teething
       tablets can make babies stop crying, but because they're made of
       lactose and sucrose (milk and sugar), not because of the
       homeopathic water.)

     * Placebos that are "more expensive" work better,^[6] as do ones that
       come in fancier packaging.^[7]

     * The effect shows a dose-response relationship like a real medical
       intervention; two pills are more effective than one.

     * More dramatic placebos are more effective. Injections work better
       than pills. A full consultation session with a doctor prior to a
       placebo is more effective than just giving a patient a pill
       dismissively.

     * The placebo effect may possibly have the ability to overpower real
       pharmacological effects. People who were given very strong drugs to
       induce nausea didn't develop symptoms as they were told the
       treatment would actually relieve nausea.^[8]

     * There are reports from war zones where saline solutions were used
       due to shortages of morphine, and proved just as effective in
       battlefield surgery.^[citation needed]

     * In one trial, the placebo effect was induced even though the
       individuals were told that it was a placebo that contains no
       medicine; although they were told that it was shown to be of help
       to people with such a condition.^[3]

     * As an indication of the wider cultural meaning and subconscious
       activity of the effect, it is observed that the colour of a sugar
       pill also affects the placebo response. Certain colours boost the
       efficacy of placebos for different illnesses, and can even
       correlate with gender.^[9]

     * The placebo effect may actually be getting stronger over time, as
       expectations about the power of medicine change,^[10] but at the
       same time it can cause drugs that are old to become weaker as the
       expectation is that new and novel treatments must be better.

     * The placebo effect may be transferable; a patient being around
       someone who believes that the treatment will work can cause the
       patient to do better - even if that person is a doctor.^[11] This
       is the reason for double-blinding in drug trials. It may also mean
       that prayer can affect patients if they know they're being prayed
       for; rigorous studies of prayer therefore make sure that there is
       no contact between prayers and patients.

     * While not related to medicine in and of itself, Tummo meditation is
       one example of the power of the placebo effect. People practicing
       it (the most famous being Wim Hof) can keep their body temperature
       warm even in extremely cold temperatures just by using their mind.

[edit] Nocebo effect

   The placebo effect has a somewhat less well-known, slightly evil
   cousin; the nocebo effect.^[12]^[13] This occurs when an individual's
   expectation of negative effects generate those effects, much like a
   hypochondriac developing symptoms because he or she is actively
   watching for something to go wrong with their health. This is
   particularly important when looking at side-effects of drugs, as a
   placebo pill can generate the negative side-effects associated with
   drugs, and in some cases, specific side-effects can be increased by
   mentioning them prominently or adding an extra layer of suggestion,
   such as complex consent forms.^[14]

   For ethical reasons the nocebo effect has not been well studied
   directly, but it is probably behind the witch doctor's ability to cause
   illness in those people he curses. It has also been used to explain
   unusual phenomenon like SUNDS (Sudden Unexpected Nocturnal Death
   Syndrome) in immigrants from the Hmong people of Laos; belief in angry
   supernatural forces combined with the phenomenon of sleep paralysis to
   convince sufferers that they were under attack, leading to extremely
   high levels of stress which could trigger dormant heart defects.^[15]

[edit] False placebo

   A false placebo is a non-placebo factor that appears to cause an
   improvement of a disease. False placebos differ from actual placebos in
   that they occur regardless of whether the patient is treated or not.
   False placebos are the lesser-known things controlled for in the
   placebo arms of clinical trials. Some examples of false placebos
   include misdiagnosis, regression to the mean, and spontaneous
   regression.

[edit] See also

     * Folk remedy
     * Correlation does not equal causation
     * Faith healing
     * Security theatre
     * Regression to the mean
     * Spontaneous improvement
     * Misdiagnosis

[edit] Footnotes

    1. ↑ Scientific American - Placebo Effect: A Cure in the Mind
    2. ↑ Analgesic effects of branding in treatment of headaches, A
       Branthwaite and P Cooper
    3. ↑ ^3.0 ^3.1 Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN,
       Kokkotou E, et al. (2010) Placebos without Deception: A Randomized
       Controlled Trial in Irritable Bowel Syndrome. PLoS ONE 5(12)
    4. ↑ Science Based Medicine - Is There a Placebo Effect for Animals?
    5. ↑ Behaviorally conditioned immunosuppression, R Ader and N Cohen,
       Psychosomatic Medicine, Vol 37, Issue 4 333-340
    6. ↑ Expensive Placebo Works Better Than Cheap One
    7. ↑ Analgesic effects of branding in treatment of headaches, A
       Branthwaite and P Cooper
    8. ↑ Wolf S. Effects of suggestions and conditioning on the action of
       chemical agents in human subjects - the pharmacology of placebos. J
       Clin Invest 1950;29:100-9. PMCID PMC439730
    9. ↑ Lucchelli, Cattaneo, Zattoni, Effect of capsule colour and order
       of administration of hypnotic treatments, European Journal of
       Clinical Pharmacology, 2004
   10. ↑ Placebos Are Getting More Effective. Drugmakers Are Desperate to
       Know Why, Wired Magazine.
   11. ↑ a) Gracely R.H,; Dubner, R.; Deeter, W.R.; Wolksee, P.J.,
       Clinclicians' expectations influence placebo analgesia. Lancet, 1,
       43 8419 (1985) b) via Ben Goldacre, Bad Science, p.75.
   12. ↑ nocebo effect
   13. ↑ New Scientist - when mind attacks body
   14. ↑ Bad Science - All bow before the mighty power of the nocebo
       effect
   15. ↑ Adler, Shelley R. Sleep Paralysis. Rutgers: 2011.

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   Submit placebo effect______

placebo effect

placebo effect

   noun

Definition of PLACEBO EFFECT

   :  improvement in the condition of a patient that occurs in response to
   treatment but cannot be considered due to the specific treatment used

First Known Use of PLACEBO EFFECT

   1950

Rhymes with PLACEBO EFFECT

   domino effect, landscape architect

placebo effect

   noun    (Medical Dictionary)

Medical Definition of PLACEBO EFFECT

   >>
   : improvement in the condition of a patient that occurs in response to
   treatment but cannot be considered due to the specific treatment used

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The placebo effect

    1. Joseph H. Friedman, MD and
    2. Richard Dubinsky, MD


   Next Section

WHAT IS A CLINICAL RESEARCH TRIAL?

   In the medical world, a clinical research trial or clinical research
   study is usually done to prove whether a new medication or therapy is
   effective, before it becomes an approved and widely used treatment.
   Patients with the target disease are often asked to take part in
   clinical research trials. To show that the new treatment is truly
   effective, it is often compared to a placebo.
   Previous SectionNext Section

WHAT IS A PLACEBO?

   Placebos are usually thought of as “sugar pills.” They are important
   “sham” or phony treatments that are used to keep doctors and patients
   honest in testing new drugs or procedures. To prove that a drug works,
   it is generally tested against a placebo: a “dummy” medication that
   should have no effect on the condition.

   Placebos are not only drugs. Sometimes patients get sham or phony
   surgery, sham radiation, or some other “pretend” treatment. Many
   patients and many doctors are unaware of the strength of “mind over
   matter.” I often tell my patients about a person who was in a study
   where the drug did not work. He insisted that the drug did work, and
   that he should be given the drug after the study ended. It turned out
   that he was not receiving the drug and that he wanted more of the
   placebo!
   Previous SectionNext Section

WHY ARE PLACEBOS IMPORTANT IN RESEARCH?

   Doctors and patients both want to see benefit from a new treatment. To
   prove that a therapy “really” works, some of the patients are given the
   sugar pill, and some get the drug. Who receives active drug and who
   receives placebo is often decided by a “coin toss” or a process called
   randomization. This process makes sure that patients are fairly divided
   between the two treatments. The change with the real drug is compared
   to the change with the placebo. The patient and doctors are not told
   until after the study is over who got the active drug and who got the
   placebo.

   Some people wonder whether it is fair or ethical to give a placebo
   treatment to a patient with a disease and not tell the patient. Many
   research studies are designed so that all patients eventually are able
   to use the study medication, even if they do not receive it at first.
   Studies are carefully reviewed to be sure that use of a placebo
   treatment does not create a dangerous situation for a patient. In the
   end, all patients benefit from studies that are carefully done using a
   placebo, so that the true effect of the treatment can be fully
   understood.
   Previous SectionNext Section

HOW DO PLACEBOS WORK?

   How placebos work is still a mystery. It is important to understand
   that not all placebo effects are good. Just as some patients improve
   with the power of positive thinking, some get worse and drop out of
   research studies because of the side effects caused by the placebo. In
   a recent, well-publicized and fascinating study of Parkinson disease
   (PD), it was discovered that the patients who improved with placebo had
   changes in their brain that were identical to the changes caused by the
   actual medication (called levodopa).^1 Levodopa causes an increase in
   brain dopamine, and the placebo should not. However, the patients who
   got better with placebo had a similar increase in dopamine, identical
   to what happened in those who were given the drug. Talk about mind over
   matter! That is like convincing yourself you can run a 40-yard dash in
   4 seconds and then doing it. Similar effects of changes in brain
   chemistry have been found in studies of pain and of depression.
   However, this does not work in secret. When patients in a study of
   treatment for pain were given pain medications without their knowledge,
   the benefit was far less than when they were given placebo and they
   were able to expect a benefit.
   Previous SectionNext Section

WHAT DID THE AUTHORS OF THIS STUDY DISCOVER ABOUT PLACEBOS?

   Diederich and Goetz^2 brought together some placebo studies in the
   areas of PD, depression, and pain, and they tried to develop a theory
   as to why the placebo effect is so large, and how it occurs. They
   reviewed studies designed to investigate how a placebo produces
   benefit. The patients with PD who thought that they were receiving the
   real treatment but who really received a placebo had the same changes
   in their brains on PET scans as those who received the medication. It
   was the expectation of the benefit that led to the same chemical
   response in the placebo group. Similar chemical changes on brain
   imaging tests were seen with placebo in studies of pain and in studies
   of depression. In the studies of PD and of pain, the more severe the
   disease symptoms and the more dramatic the treatment (surgery,
   injection that the patient can see rather than by a pump), the more
   likely the subjects were to experience benefit with placebo treatment.

   Why should brain chemistry change when patients are convinced they are
   receiving a treatment and their physicians expect them to improve? It
   seems that the expectation of benefit activates the same natural
   pathways in the brain as medications. If we could harness these same
   mechanisms in the clinic, patients could help themselves without the
   side effects of medications.
   Previous SectionNext Section

WHY ARE THESE STUDIES IMPORTANT? WHAT DOES THE FUTURE HOLD?

   The authors point out that placebo effects make the study of new
   treatments very difficult. This is because the effect of a new
   treatment has to be much greater than the placebo effect, which can be
   quite large.

   If the placebo effect is strong, it is harder to prove that a drug or
   treatment is effective. This means that most research trials have to
   use many more people than they would if the placebo effect was very
   small or did not exist at all. This makes the studies cost more and
   take longer to accomplish. Better understanding of the placebo effect
   will help us to design faster, more effective studies to better combat
   disease. Perhaps one day we will also learn how to better harness the
   positive parts of the placebo effect to use as part of medical therapy.
   Previous SectionNext Section

Footnotes

     * Series editor: David C. Spencer MD, Section Editor Steven Karceski
       MD, Section Editor

   Previous Section

REFERENCES

    1. 1.↵
       de la Fuente-Fernandez R, Ruth TJ, Sossi V, et al. Expectation and
       dopamine release: mechanism of the placebo effect in Parkinson's
       disease. Science 2001;293:1164–1166.
       Abstract/FREE Full Text
    2. 2.↵
       Diederich NJ, Goetz CG. The placebo treatments in neurosciences:
       new insights from clinical and neuroimaging studies. Neurology
       2008;71:677–684.
       Abstract/FREE Full Text

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    1. Top
    2. WHAT IS A CLINICAL RESEARCH TRIAL?
    3. WHAT IS A PLACEBO?
    4. WHY ARE PLACEBOS IMPORTANT IN RESEARCH?
    5. HOW DO PLACEBOS WORK?
    6. WHAT DID THE AUTHORS OF THIS STUDY DISCOVER ABOUT PLACEBOS?
    7. WHY ARE THESE STUDIES IMPORTANT? WHAT DOES THE FUTURE HOLD?
    8. Footnotes
    9. REFERENCES

    1. doi: 10.1212/01.wnl.0000326599.25633.bb Neurology August 26, 2008
       vol. 71 no. 9 e25-e26

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   Cover Image: February 2009 Scientific American Magazine See Inside

Placebo Effect: A Cure in the Mind [Preview]

   Belief is powerful medicine, even if the treatment itself is a sham.
   New research shows placebos can also benefit patients who do not have
   faith in them

   By Maj-Britt Niemi

   [pin_it_button.png]
   Image: © ISTOCKPHOTO

In Brief

     * In recent decades reports have confirmed the efficacy of various
       sham treatments in nearly all areas of medicine. Placebos have
       helped alleviate pain, depression, anxiety, Parkinson’s disease,
       inflammatory disorders and even cancer.
     * Placebo effects can arise not only from a conscious belief in a
       drug but also from subconscious associations between recovery and
       the experience of being treated—from the pinch of a shot to a
       doctor’s white coat. Such subliminal conditioning can control
       bodily processes of which we are unaware, such as immune responses
       and the release of hormones.
     * Researchers have decoded some of the biology of placebo responses,
       demonstrating that they stem from active processes in the brain.

   A man whom his doctors referred to as “Mr. Wright” was dying from
   cancer of the lymph nodes. Orange-size tumors had invaded his neck,
   groin, chest and abdomen, and his doctors had exhausted all available
   treatments. Nevertheless, Mr. Wright was confident that a new
   anticancer drug called Krebiozen would cure him, according to a 1957
   report by psychologist Bruno Klopfer of the University of California,
   Los Angeles, entitled “Psychological Variables in Human Cancer.”

   Mr. Wright was bedridden and fighting for each breath when he received
   his first injection. But three days later he was cheerfully ambling
   around the unit, joking with the nurses. Mr. Wright’s tumors had shrunk
   by half, and after 10 more days of treatment he was discharged from the
   hospital. And yet the other patients in the hospital who had received
   Krebiozen showed no improvement.

   This article was originally published with the title Cure in the Mind.
   To read the rest of this article, we recommend purchasing and
   downloading the digital issue from a computer. Email this article link
   for reference.
   [rightsPermsIcon.png] Rights & Permissions

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   Home → Articles → The Placebo Effect

The Placebo Effect

   Posted by Steven Novella on January 16, 2008 (25 Comments)

   Recently the Federal Trade Commission went after the makers of the
   Q-Ray Ionized Bracelet for their claims that their device was a cure
   for chronic pain. Last week Seventh Circuit judge Frank Easterbrook
   handed down his opinion on the company’s appeal, writing that the
   company was guilty of fraud and ordering them to pay 16 million dollars
   in fines. One of the key points for the company’s defense was that the
   Q-Ray Ionized Bracelet is legit because it exhibits the placebo effect.
   Judge Easterbrook was not impressed with this argument, writing:

     “Like a sugar pill it alleviates symptoms even though there is no
     apparent medical reason. Since the placebo effect can be obtained
     from sugar pills, charging $200 for a device that is represented as
     a miracle cure but works no better than a dummy pill is a form of
     fraud.”

   This decision creates an interesting precedent, since there are a large
   number of fanciful treatments that do not have any “apparent medical”
   mechanism and that are claimed by its proponents to work through a
   placebo effect. In my experience the placebo effect, briefly defined as
   a measurable response to an inert treatment, is almost completely
   misunderstood by the public – a fact that is exploited by purveyors of
   dubious treatments such as the Q-ray. Already in the comments of this
   blog there has been discussion over the nature of the placebo effect.

   In order to demystify the placebo effect, I will try to first describe
   exactly what it is. The operational definition of a placebo effect is
   any health effect measured after an intervention that is something
   other than a physiological response to a biologically active treatment.
   In clinical trials the placebo effect is any measured response in the
   group of study subjects that received an inert treatment, such as a
   sugar pill. However, “the placebo effect” is a misnomer and contributes
   to confusion, because it is not a single effect but the net result of
   many possible factors.

   The various factors that contribute to a measured or perceived placebo
   effect vary depending upon the situation – what symptoms or outcomes
   are being observed. Subjective outcomes like pain, fatigue, and an
   overall sense of wellbeing, are subject to a host of psychological
   factors. For example, subjects in clinical studies want to get better,
   they want to believe they are on the active experimental treatment and
   that it works, they want to feel that the time and effort they have
   invested is worthwhile, and they want to make the researchers happy. In
   turn, the researchers want their treatment to work and want to see
   their patients get better. So there is often a large reporting bias. In
   other words, subjects are likely to convince themselves they feel
   better, and to report that they feel better, even if they don’t. Also,
   those conducting a trial will tend to make biased observations in favor
   of a positive effect.

   It has also been clearly demonstrated that subjects who are being
   studied in a clinical trial objectively do better. This is because they
   are in a clinical trial – they are paying closer attention to their
   overall health, they are likely taking better care of themselves due to
   the constant reminder of their health and habits provided by the study
   visits and attention they are getting, they are being examined on a
   regular basis by a physician, and their overall compliance with
   treatment is likely to be higher. So basically, subjects in a trial
   take better care of themselves and get more medical attention than
   people not in trials. If for those not in a clinical trial, if they
   decide to do something about their health by starting a new treatment,
   they are likely to engage in more healthful behavior in other ways.

   A common belief is that the placebo effect is largely a
   “mind-over-matter effect,” but this is a misconception. There is no
   compelling evidence that the mind can create healing simply through
   will or belief. However, mood and belief can have a significant effect
   on the subjective perception of pain. There is no method to directly
   measure pain as a phenomenon, and studies of pain are dependent upon
   the subjective report of subjects. There is therefore a large potential
   for perception and reporting bias in pain trials. But there are
   biological mechanisms by which mental processes can affect pain. There
   are many non-specific factors that can biochemically suppress pain. For
   example, increased physical activity can release endorphins that
   naturally inhibit pain. For these reasons the placebo effect for pain
   is typically high, around 30%.

   But the more concrete and physiological the outcome, the smaller the
   placebo effect. Survival from serious forms of cancer, for example, has
   no demonstrable placebo effect. There is a “clinical trial effect,” as
   described above – being a subject in a trial tends to improve care and
   compliance, but no placebo effect beyond that. There is no compelling
   evidence that mood or thought alone can help fight off cancer or any
   similar disease.

   Other conditions are more objective than pain, but are special because
   they have a strong influence from the neuro-endocrine system. This
   system translates psychological stress into physical stress, by
   releasing stress hormones and increasing activity in the sympathetic
   nervous system. So, for example, for heart disease mood matters quite a
   bit. Someone who has an A-type personality and is always angry and
   upset is at higher risk of a heart attack than someone who is mellow
   and unstressed. But here there is a known physiological connection
   between mood and a specific organ – the heart. This cannot be
   extrapolated to other diseases; it doesn’t mean you can smile your
   cancer away.

   Many people talk about the neuroendocrine system’s effect on the immune
   system. Again, here there is a physiological connection. Stress
   hormones do suppress the immune system, and it is probably true that
   extreme stress leaves us physically susceptible to disease for this
   reason. But the effects of moderate levels of stress are not
   established. Also, we cannot extrapolate from the risk of getting a
   cold to the ability to fight off cancer. You have to look at the
   evidence for each disease unto itself. So while this is a potential
   contributor, it is overall probably a small effect except in extreme
   situations.

   The lack of any real biological placebo effect has led some to question
   the necessity of having a placebo control in clinical trials. However,
   I feel there is still a need for a double-blind placebo-controlled
   design for most clinical trials because that is the only way to
   minimize the effects of bias on trial outcomes. The factors I listed
   above will still create the illusion of an effect and the only way to
   control for this is with a placebo group.

   Therefore the placebo effect is fairly complex and is largely an
   artifact of observation and confounding factors. Any real benefits that
   contribute to the placebo effect can be gained by more straightforward
   methods – like healthy habits, compliance with treatment, and good
   health care. The placebo effect is not evidence for any mysterious
   mind-over-matter effect, but since the mind is matter (the brain) and
   is connected to the rest of the body, there are some known
   physiological effects that do play a role (although often greatly
   exaggerated).

   In light of all this, I do not feel that knowingly prescribing a
   placebo treatment is effective or ethical medicine. Modern scientific
   medicine should strive for interventions that physiologically are
   scientifically plausible and have sufficient evidence for safety and
   effectiveness. But I do think there are lessons to be learned from the
   placebo effect – there are aspects of therapy that do go beyond the
   physiological intervention. Medicine is not only an applied science; it
   is the art of humans treating other humans. As part of effective
   treatment it is helpful to try to maximize all those human intangibles
   that contribute to a good outcome. But we can do this in the context of
   scientifically valid treatment, and without crossing the ethically
   dubious line of deception.

   I therefore heartily agree with Judge Easterbrook that invoking the
   placebo effect is not a defense for making fraudulent health claims,
   for the Q-ray or any other implausible treatment.

   Posted in: Clinical Trials, Science and Medicine
   Leave a Comment (25) ↓

25 thoughts on “The Placebo Effect”

    1. PalMD says:
       January 16, 2008 at 8:53 am
       I agree that it is ethically impermissible for doctors to prescribe
       placebos, as it involves actively deceiving a patient.
       It is *not* ethically unsound to “hype” a treatment, in that if a
       patient has confidence in a treatment they are more likely to be
       compliant, etc. For example, I often will tell a patient that the
       medical regimen for their heart disease will help prevent them from
       dying, etc (which is true), making them (I hope) more likely to
       stick to it. I work with residents every day, and many of them have
       not learned that yet (I’m working on it!).
       But creating confidence in a treatment/physician/relationship is
       not placebo—just good medicine.
    2. Apreche says:
       January 16, 2008 at 10:19 am
       I also agree that it is unethical to prescribe placebos to people
       who have true illness. However, I am torn on whether it is ethical
       to prescribe them to hypochondriacs.
       If someone believes they are ill, when they are not, then perhaps a
       placebo is a good treatment as long as it is in combination with
       proper psychological treatment as well. One alternative seems to be
       to either give them a real treatment for a condition they only
       believe they have, which is clearly out of the question. The other
       option seems to be to just send them home telling them they are not
       ill. That option would seem to result in them turning to
       pseudoscience for help.
       I guess that just the psychological treatment alone would be
       ethically ideal, but since it won’t be effective immediately, it
       may still result in a turn towards fraudulent treatments.
       I’m a tech person, not a doctor, so obviously I have no clue what
       I’m talking about. I’d love to hear what experts have to say about
       this issue, and that is why I like this blog.
    3. daedalus2u says:
       January 16, 2008 at 12:16 pm
       As someone who has thought a great deal about the placebo effect in
       the context of my NO research I have a slightly different
       perspective. I would distinguish between non-physiological effects,
       such as investigator bias, and what I consider to be the “true”
       placebo effect mediated through physiology. I appreciate that this
       distinction may be difficult (if not impossible) to make
       experimentally unless specifically looked for (which most trials
       don’t). In the context of treatment the distinction doesn’t much
       matter. In the context of clinical trials it can. A single blinding
       (of patients) might work to correct for the physiological placebo
       effect mediated though patient physiology, investigator blinding is
       necessary to correct for investigator bias. In clinical trials
       double blinding corrects for both, which is why it is the gold
       standard for clinical trials.
       I completely agree that prescribing placebos has no place in any
       treatment modality. There are plenty of lifestyle changes that can
       be prescribed, diet, exercise, weight loss, stress relief that will
       do the same things and much more reliably than a placebo
       medication. Learning how to relax via the relaxation response
       http://www.mbmi.org/about/default.asp
       invokes all of these same pathways (as I understand them), and
       again more reliably than any placebo.
       I know that my views of the mechanisms and magnitude of the
       physiological effects of the placebo effect are larger than what is
       considered “main stream”, however the most I see the placebo effect
       doing is restoring physiology to the “default” base-line state of
       normal health. I can think of no mechanism(s), by which the placebo
       effect would be effective at treating cancer, infections, trauma,
       or any disorder not caused by chronic stress. Even then it works as
       a preventative to prevent future damage, not to correct damage
       already done.
    4. BlazingDragon says:
       January 16, 2008 at 2:00 pm
       This discussion is interesting and touches on an issue I have
       strong feelings about. Is someone a hypochondriac or do they have a
       relatively rare disease (or a rare manifestation of a more common
       diseaese)? Too many physicians make the assumption, if simple lab
       tests do not show anything, that the patient is a hypochondriac.
       They prescribe therapies to get the patients to “shut up,” hoping
       the “placebo effect” will give the patients relief.
       This discussion about the placebo effect and how it is unethical to
       prescribe therapies mostly (or wholly) intended to get a patient to
       stop calling the doctor miss the fact that it happens often in real
       practice.
       Discussions like these are extremely frustrating to me because they
       talk about an idealized medicine standard that is rarely met these
       days in actual practice. The time/money constraints put on doctors
       render ideals pretty much moot for the general public that contacts
       the health care delivery system these days. I’m all for these
       discussions on how to make medicine better, but we also need to
       find ways to make these ideals a much larger part of everyday
       clinical practice.
       I firmly believe that clinical trials with double-blinded,
       placebo-controlled designs are the only validation for therapies.
       Just because someone “thinks” a therapy might be effective doesn’t
       make it so, even if the therapy is a new application for an
       approved drug (see the whole Zetia mess). But Apreche has a very
       relevant point about people turing to pseudo-science if they feel
       ignored by the “system.”
       I watch a lot of Discovery channel shows, so I saw this “ionizing
       bracelet” crap years ago and couldn’t believe they were selling it
       (it’s kind of sad how Discovery has to finance themselves with
       pseudo-science crap because “real” advertisers don’t advertise on
       “science” channels). I’m glad to see they got their come-uppance
       and the judge hit on exactly the reason why they are frauds.
       I wonder how long those japanese toxin-removing foot-pads I’ve seen
       lately on Discovery will be allowed to sell their crap before they
       are busted for pseudo-science too (they make even more radical and
       testable claims about being able to withdraw toxins and heavy
       metals by sleeping with their special pads stuck to the bottom of
       your feet).
    5. Calli Arcale says:
       January 16, 2008 at 4:35 pm
       I have a relative (now long since retired) who used to prescribe
       placebos for particularly troublesome patients whom he deemed to be
       hypochondriacs — only they weren’t just sugar pills, they actually
       were a drug that caused mild nausea. He would warn patients to
       expect mild nausea as evidence that it was working. They’d go away
       happy, then come back to report on how well the medicine had
       worked. When I was younger, I used to think that was a shrewd idea
       on his part. Now that I’m mature, I find myself wondering if this
       was part of the reason why he suddenly had to move his practice
       five hundred miles west (and into another state) just a few years
       shy of retirement.
       What he did was actually *worse* than mere deception, since
       evidently what he gave the patient actually did have an affect, and
       an unpleasant one at that.
    6. Pingback: Placebo–tool or weapon? « WhiteCoat Underground
    7. Roy Niles says:
       January 16, 2008 at 5:26 pm
       When you talk about treatment “without crossing the ethically
       dubious line of deception,” are you inferring that deception is
       ethically dubious per se, or that there is a line between
       acceptable and unacceptable forms of deception.
       I would presume you mean the latter, but even so, the standards for
       determining where that line is crossed might be a good subject for
       further discussion.
    8. psamathos says:
       January 16, 2008 at 8:54 pm
       Thanks for the interesting write-up. I also found Mark Crislip’s
       podcast about the placebo effect informative, if anyone else is
       looking for more information on misconceptions about the placebo
       effect:
       http://www.quackcast.com/QuackCast/Podcasts/Entries/2006/5/22_Quack
       Cast_5._Placebo_Effect.html
    9. daedalus2u says:
       January 16, 2008 at 9:19 pm
       I think that any deception in any (purported) therapeutic setting
       is unethical. I actually think that deception in any setting where
       there is an expectation of trust is unethical and is a violation of
       any type of professional conduct.
   10. Roy Niles says:
       January 17, 2008 at 12:29 am
       There are aspects of deception, both passive and active, that are
       considered ethical and moral, and that exist in different ways in
       every profession (and every culture for that matter). It may seem
       paradoxical, but trust depends on knowing those in that profession
       understand the difference, and apply that understanding in the best
       interests of their clients. Problems arise when the “cultural”
       standards of the particular profession are violated, ignored,
       twisted, subverted, and when there is no clear agreement as to what
       those standards should be, and no clear method of enforcing them.
   11. Steven Novella says:
       January 17, 2008 at 10:30 am
       The question of deception, that I only touched upon in this entry,
       is a very interesting and important one so I think I will write a
       thorough treatment of it for my blog entry next week. Stay tuned.
   12. daedalus2u says:
       January 17, 2008 at 6:03 pm
       For me, my complete unwillingness to be deceptive relates to my
       knowledge that I do make mistakes. When I am in a position of
       trust, my mistakes can hurt people who are trusting me and who I
       don’t want to hurt. Being as truthful with those who are relying on
       me as I am with myself relieves me of (most) any guilt due to
       error.
   13. daedalus2u says:
       January 18, 2008 at 8:42 am
       Another reason I don’t like to be deceptive is because the “best”
       way to lie is to also lie to yourself that is to believe the lie
       that you are telling. Figuring out physical reality is difficult
       enough as it is without injecting lies into it. One you start
       spreading lies, you start believing lies. When you believe in lies,
       even “harmless” ones, your conceptualization of reality breaks down
       and it becomes unreliable.
       In the context of administering placebos, if you started to do it
       and saw that they “worked”, it wouldn’t take much rationalization
       to ascribe mechanisms beyond that of the placebo effect. It is a
       slippery slope that could take you down into the abyss of quackery.
   14. Roy Niles says:
       January 19, 2008 at 4:24 pm
       As someone once said, one aspect of deception involves the process
       of persuading yourself you haven’t just engaged in self-deception.
   15. rjstan@together.net says:
       January 19, 2008 at 7:22 pm
       I think one of the best ways to start to understand the placebo
       effect is to speak with scientists who develop drugs or with the
       stock brokers who follow the industry. The scientists tell tales of
       experimenting for years on substances that they believed were going
       to cure horrible diseases only to find out as they tested further
       that they had been wrong.
       When you deal with an organism as complex as a living human being,
       there are many unknown variables which affect the course of a
       disease. The placebo effect is an umbrella term used to cover them
       all. While double-blind clinical trials will tell you if a drug is
       effective, they will not tell you what has caused significant
       improvement in any particular test subject receiving a placebo.
       In my experience it is very difficult for many people, especially
       many people in engineering and the “hard sciences” to accept and
       deal with the unknown variables in medicine. It is the reason that
       many are taken in by “alt med” and claims which may sound logical
       but which cannot be supported by evidence, such as the claim that a
       supplement that kills bacteria in vitro will also do that in vivo.
   16. overshoot says:
       January 22, 2008 at 12:09 pm
       rjstan@together.net:
       “In my experience it is very difficult for many people, especially
       many people in engineering and the “hard sciences” to accept and
       deal with the unknown variables in medicine. It is the reason that
       many are taken in by “alt med” and claims which may sound logical
       but which cannot be supported by evidence, such as the claim that a
       supplement that kills bacteria in vitro will also do that in vivo.”
       I think that very much depends on the “hard science” in question.
       Certainly physics and electronics do so much in the realm of
       quantum mechanics that we have no excuse for not appreciating the
       chaotic nature of complex systems.
       As for the vitro/vivo issue, please correct me if I’m wrong but
       IIRC it’s pretty safe to say that an agent that is bactericidal in
       vitro _will_ also kill them in vivo; it’s just that you can crank
       up the concentrations in vitro to levels that would be unattainable
       or intolerable in vivo. My current favorite is the bunch pushing
       various forms of silver as a magical antibacterial. They promote
       low concentration systemic use while citing high concentration
       topical use to argue effectiveness.
   17. Pingback: Science Based Medicine » The Ethics of Deception in
       Medicine
   18. Pingback: Transparent Eye » Blog Archive » The Placebo Effect
   19. Pingback: Science-Based Medicine » The Role of Anecdotes in
       Science-Based Medicine
   20. Pingback: Science-Based Medicine » Homeopathy and Evidence-Based
       Medicine: Back to the Future Part V
   21. Pingback: NeuroLogica Blog » The Price of Placebos
   22. Pingback: Science-Based Medicine » Be Wary of Stem Cell
       Pseudoscience
   23. Pingback: Science-Based Medicine » Studying Placebo Effects
   24. Pingback: The Placebo Effect « FreeThought Fort Wayne
   25. Pingback: Science-Based Medicine » Placebos in the news again

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Placebo effect

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     * Noma Bar 22032013

George Osborne's sugar pills won't heal the pain, but Julia Gillard's may
       21 Mar 2013: Gaby Hinsliff: The placebo effect has its place beyond
       medicine – as long as those who soothe us do so with our best
       interests at heart
     *

The placebo effect is present in every medical intervention
       21 Mar 2013: Philippa Perry: The western concept of an autonomous
       self does not account for how a doctor's beliefs can influence the
       patient's health
     *

Science Weekly podcast: Jim Al-Khalili on the wonders of quantum biology
       A male robin Audio (50min 20sec), 17 Sep 2012:
       On this week's show we also hear about new research into the
       placebo and nocebo effects, and from IgNobel master of ceremonies
       Marc Abrahams on why great science can be both funny and profound
     *

Subconscious cues can trigger the placebo effect, say researchers
       11 Sep 2012: The finding that there are subliminal influences on
       the placebo effect has implications for how healthcare is delivered
     *

Why I changed my mind about homeopathy
       3 Apr 2012:
       Edzard Ernst: There can be no doubt – people get better after
       consulting a homeopath, and the reason is clear
     *

Pavlov and placebos could reduce the side-effects of drug treatments
       Drug capsules 23 Mar 2012: Corrinne Burns: A new study suggests
       patients can be conditioned to respond to a placebo in place of a
       drug, allowing doses to be reduced
     *

The nocebo effect: Wellcome Trust science writing prize essay
       13 Nov 2011:
       Penny Sarchet discusses research on the 'nocebo' effect in her
       winning essay for the Wellcome Trust science writing prize, awarded
       in association with the Guardian and Observer
     *

Detox: flushing out poison or absorbing dangerous claptrap?
       29 Aug 2011:
       The alternative-medicine version of detox has real-world
       side-effects that outweigh its imaginary benefits
     *

Is Avram Grant football's placebo effect?
       avram grant 14 Jul 2011: Harry Pearson: Scientists may have solved
       the mystery of how Avram Grant keeps getting top-level coaching
       jobs
     *

Placebos may help us but they don't have the same effect as medicine
       16 Mar 2011:
       Response: There's a lot of confusion over the nature of the inert
       dummy pills used in drug trials, says Tom Burns
     *

Half of all German doctors prescribe placebos, new study shows
       6 Mar 2011:
       Placebo cures shown to help with depression and stomach complaints
       – in Bavaria, 88% of doctors have prescribed them
     *

How security can be more theatre than reality
       UK Border Agency drug detection 26 Feb 2011:
       Ben Goldacre: Drug-detecting dogs and hi-tech brain scans to spot
       liars – examples of how we are still buying into the placebo effect
     *

Placebos, again
       21 Feb 2011:
       Andrew Brown: Placebos work because people believe in them. So what
       do we make of a study that shows they work even when patients are
       told they are sugar pills?
     *

The strange powers of the Placebo Effect
       15 Feb 2011:
       Hypothesis: some people experience relief of some health symptoms
       simply by believing that a substance will make them feel better
     *

Celebrity endorsements that are science fiction trashed in annual list
       A Power Balance silicone bracelet containing a hologram 29 Dec
       2010:
       Campaigners name and shame stars for dodgy health and diet claims

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The placebo effect

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   The placebo effect

   When a person uses any type of health treatment and sees an improvement
   in their symptoms, they may be experiencing the placebo effect. That’s
   why it’s important to be aware of the placebo effect when judging the
   effectiveness of a treatment, or when using one ourselves.

   The placebo effect is about the power of the mind to influence the
   body.

   It can occur when a person uses any kind of health treatment, either
   conventional or complementary and alternative.

   It can affect all of us, whether we know about the placebo effect or
   not.

   It’s important to be aware of the placebo effect when choosing
   complementary and alternative treatments. That is because if we choose
   a complementary or alternative treatment that does not work – and
   causes only a placebo effect – we may miss out on more effective
   treatments.

What is the placebo effect?

   For hundreds of years, doctors have known that when a patient with a
   health condition expects their symptoms to improve, they often do
   improve.

   Today, we know that patients who are given empty injections or pills
   that they believe contain medicine can experience improvement in a wide
   range of health conditions. This kind of fake or empty medicine is
   often called a placebo, and the improvement that results is called the
   placebo effect.

   The placebo effect is an example of how our expectations and beliefs
   can cause real change in our physical bodies. It’s a phenomenon that we
   don’t completely understand. But we can see it working in all kinds of
   ways, and all kinds of circumstances.

The placebo effect at work

   Take one well-known example based on a physical feeling we are all
   familiar with: pain.

   In 1996, scientists assembled a group of students and told them that
   they were going to take part in a study of a new painkiller, called
   'trivaricaine'. Trivaricaine was a brown lotion to be painted on the
   skin, and smelled like a medicine. But the students were not told that,
   in fact, trivaricaine contained only water, iodine, and thyme oil, none
   of which are painkilling medicines. It was a fake – or placebo –
   painkiller. Read an abstract of the study: Mechanisms of Placebo Pain
   Reduction.

   With each student, the trivaricaine was painted on one index finger,
   and the other left untreated. In turn, each index finger was squeezed
   in a vice. The students reported significantly less pain in the treated
   finger, even though trivaricaine was a fake.

   In this example, expectation and belief produced real results. The
   students expected the 'medicine' to kill pain: and, sure enough, they
   experienced less pain. This is the placebo effect.

   Placebo medicine has even been shown to cause stomach ulcers to heal
   faster than they otherwise would.

   These amazing results show that the placebo effect is real, and
   powerful. They mean that fake or placebo treatments can cause real
   improvements in health conditions: improvements we can see with our own
   eyes.

   Experiencing the placebo effect is not the same as being 'tricked', or
   being foolish. The effect can happen to everyone, however intelligent,
   and whether they know about the placebo effect or not.

CAM and the placebo effect

   Evidence about a treatment is gathered by conducting fair tests. In
   these tests, scientists find out whether a treatment causes an
   improvement beyond the improvement caused by the placebo effect alone.

   Evidence plays an important role in mainstream medicine. This means
   that when you use many conventional medicines, you can be sure that
   there is evidence that they work.

   When patients experience improvement after using a healthcare treatment
   that has not been proven to work, they may be experiencing only the
   placebo effect.

   Of course, improvement in a health condition due to the placebo effect
   is still improvement, and that is always welcome.

   But it is important to remember that for many health conditions, there
   are treatments that work better than placebo treatments. If you choose
   a treatment that provides only a placebo effect, you will miss out on
   the benefit that a better treatment would provide.

Check the evidence

   The only way to know whether a health treatment works better than a
   placebo treatment is by checking the evidence.

   You can learn more about evidence, how it is gathered, and why it is
   important in CAM: what is evidence?.

   You can learn about the evidence for many of the best-known
   complementary and alternative medicines in the Health A-Z pages.

   Page last reviewed: 23/11/2012

   Next review due: 23/11/2014

   More articles on: Complementary and alternative medicine

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Comments

   The 1 comments about ‘The placebo effect’ posted are personal views.
   Any information they give has not been checked and may not be accurate.

rationallawful said on 04 February 2013

   You rightly say 'of course, improvement in a health condition due to
   the placebo effect is still improvement, and that is always welcome';
   however sadly certain scientists who should know better wrongly equate
   'placebo' with 'invalid' and 'contrary to evidence based medicine' and
   then go on to bad-mouth complementary therapies including homeopathy
   which they say should be banned. The greatest strength of the NHS is
   that it is COMPREHENSIVE - see the 2012 Health and Social Care Act
   (Section 1.1): 'The Secretary of State must continue the promotion in
   England of a comprehensive health service designed to secure
   improvement— .(a) in the physical and mental health of the people of
   England, and (b) in the prevention, diagnosis and treatment of physical
   and mental illness’.
   The time has come to find a better word than 'Placebo' which generates
   more heat than light. It wraps up a lot of heterogeneous concepts into
   a single word which is then meaningless in a scientific sense. This
   point has been taken up in the July 2012 in-depth (294 page) doctoral
   dissertation 'Evidence-based medicine, "placebos" and the homeopathy
   controversy' by Dr Andrew James Turner of the University of Nottingham
   at
   http://etheses.nottingham.ac.uk/2577/
   which shows (page 185) that lumping a disparate range of elements
   together only adds to the confusion; if one wishes to say something
   informative about medical treatments, ‘placebo’ and ‘placebo effect’
   are not terms which are analytically useful. Better to talk about
   'components of treatment' one or more of which can contribute towards
   the effectiveness of a therapy.
   A growing body of published research in good quality peer-reviewed
   journals shows that homeopathy has a positive effect. Healthcare is
   about adding years to life and life to years and homeopathy when
   practised (as it is)and integrated by qualified medical practitioners
   time and time again demonstrates that it is economic al, safe, and
   effective.

   Report this content as offensive or unsuitable comment id 33818

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   Ben Goldacre explains what the placebo effect is and describes its role
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   Home > Conditions and treatments > Medications - Introduction to
   medications > Placebo effect

Placebo effect

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   Placebo effect

Summary

   A placebo is any medical treatment that is inert (inactive), such as a
   sugar pill. Around one third of people who take placebos (believing
   them to be medication) will experience an end to their symptoms. This
   is called the placebo effect.
   Download the PDF version of this fact sheet Email this fact sheet

   Placebo is Latin for 'I will please', and refers to any medical
   treatment that is inert. The placebo has long been used in research
   trials to objectively test the efficacy of a new health care treatment,
   such as a drug. A placebo is indispensable to the conduct of many
   scientifically-based clinical trials. Ethical considerations require
   that participants in clinical trials be told that they may be given a
   'dummy' treatment.
   Usually, one group of people takes the drug while another group (the
   control group) takes the placebo. The placebo may be a sugar pill. None
   of the participants know whether they are taking the active or inactive
   substance. Sometimes, not even the researchers know (double blind
   test).
   Comparing the results from both groups should indicate the effects of
   the drug. However, people sometimes get better when they are taking a
   placebo. This phenomenon is known as 'the placebo effect'. Estimates
   vary, but around one third of people taking placebos for complaints
   (including pain, headache and seasickness) will experience relief from
   symptoms. There are various theories that attempt to explain this
   phenomenon but the underlying mechanisms remain mysterious.

Types of placebos

   A placebo doesn't have to be a pill. It can be any inert or 'dummy'
   treatment, such as special diets, exercise, physical therapy or even
   surgery. The placebo effect is triggered by the person's belief in the
   treatment and their expectation of feeling better, rather than the
   specific form the placebo takes.

The misconception of 'imaginary' disorders

   If a person's symptoms are relieved by taking an inert substance or
   undergoing a dummy procedure, it seems logical to assume that their
   illness must have been imaginary. This is not the case. Medical
   research has shown that psychological states play an important role in
   the development of disease. For example, stress is known to increase
   blood pressure, and chronic hypertension is a risk factor for heart
   disease. Just as the mind can contribute to a physical disorder, it can
   also contribute to its cure.

Influencing factors

   Some of the factors that influence the placebo effect include:
     * The characteristics of the placebo - if the pill looks genuine, the
       person taking it is more likely to believe that it contains
       medicine. Research shows that larger sized pills suggest a stronger
       dose than smaller pills, and taking two pills appears more potent
       than swallowing just one. Generally, injections have a more
       powerful effect than pills.
     * The person's attitude - if the person expects the treatment to
       work, the chances of a placebo effect are higher. Some studies show
       that the placebo effect may still take place even if the person is
       sceptical of success. The power of suggestion may be at work here.
     * Doctor-patient relationship - if the person trusts their health
       care practitioner, they are more likely to believe that the placebo
       will work.

How placebos work

   The exact physiological mechanisms remain mysterious. Some of the
   theories that attempt to explain the placebo effect include:
     * Self-limiting disorders - many conditions, such as the common cold,
       are self-limiting. They will resolve by themselves anyway, with or
       without placebos or drugs, and the end of symptoms is merely
       coincidence.
     * Remission - the symptoms of some disorders, such as multiple
       sclerosis and lupus, may wax and wane. A remission during a course
       of placebos may be coincidence, and not due to the placebos at all.
     * A change in behaviour - the placebo may increase a person's
       motivation to take better care of themselves. Improved diet,
       regular exercise or rest may be responsible for the easing of their
       symptoms.
     * Altered perception - the person's interpretation of their symptoms
       may change with the expectation of feeling better. For example, a
       sharp pain may be reinterpreted as an uncomfortable tingling.
     * Reduced anxiety - taking the placebo and expecting to feel better
       may soothe the autonomic nervous system and reduce the levels of
       stress chemicals, such as adrenaline.
     * Brain chemicals - placebos may trigger the release of the body's
       own natural painkillers, the brain chemicals (neurotransmitters)
       known as endorphins.
     * Altered brain state - research indicates that the brain responds to
       an imagined scene in much the same way as it responds to an actual
       visualised scene. A placebo may help the brain to remember a time
       before the onset of symptoms, and then bring about physiological
       change. This theory is called 'remembered wellness'.

The argument against placebos

   Placebos have the power to cause unwanted side effects. Nausea,
   drowsiness and allergic reactions, such as skin rashes, have been
   reported as placebo effects. Critics of placebos maintain that
   deception is wrong, regardless of whether the deceived patient
   experiences an end to their symptoms. The longterm prescription of
   placebos by an unscrupulous health care practitioner may also convince
   an otherwise healthy person that they are suffering from an illness or
   infection that requires ongoing treatment. The mind-set of believing
   oneself to be ill may contribute to the onset of genuine symptoms. A
   good doctor-patient relationship with good communication is usually
   preferable to the use of a placebo.

The placebo effect is doubted by some

   Some researchers doubt the placebo effect even exists. For example,
   medical philosophers at the University of Copenhagen recently analysed
   trials that involved placebos and declared that placebos offered about
   the same degree of symptom relief as no medical treatment. Critics
   point out that the methodology used by the medical philosophers was
   flawed, and that the placebo effect has been well documented for many
   years.

Where to get help

     * Your doctor

Things to remember

     * A placebo is any medical treatment that is inert, such as a sugar
       pill.
     * Around one third of people who take placebos (believing them to be
       medication) will experience an end to their symptoms.
     * Belief in a treatment may be enough to change the course of a
       person's physical illness.

You might also be interested in:
          + Clinical trials.

Want to know more?
       Go to More information for support groups, related links and
       references.

This page has been produced in consultation with and approved by:
       Monash University - Centre for Developmental Psychiatry and
       Psychology
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       Monash University - Centre for Developmental Psychiatry and
       Psychology
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       A placebo is any medical treatment that is inert (inactive), such
       as a sugar pill. Around one third of people who take placebos
       (believing them to be medication) will experience an end to their
       symptoms. This is called the placebo effect.
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   Season 3 | Episode 1

Placebo

   « previous episode | next episode »
   Jacob Smullyan
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   Stream m3u
   Pill Pill (Lucas Lucas/flickr/CC-BY-2.0)

   With new research demonstrating the startling power of the placebo
   effect, this hour of Radiolab examines the chemical consequences of
   belief and imagination.
     * Podcasts More

   Could the best medicine be no medicine at all? We take stock of the
   pharmacy in our brains, consider the symbolic power of the doctor coat,
   and visit the tent of a self-proclaimed faith healer.

Guests:

   Dr. Naji Abumrad, Fabrizio Benedetti, preacher Steve Buza, Dr. Daniel
   Carr, Ed Cohen, Ann Harrington, Dr. Albert Mason, Daniel Moerman and
   Tor Wager
    Tags:
     * brain
     * idea explorer
     * medicine
     * mind bending

   pills

Pinpointing the Placebo Effect

   All over the world, people say they are healed by things that turn out
   to be placebo. So it's easy to think that they must have been faking in
   the first place if all it took was a little sugar pill to assuage their
   ailments. But keep your scoffing at ...

   Comments [22]
   white lab coat

The White Coat

   Next up: a look at the placebo effect from the doctor's perspective.
   How the medical context alone can be the key into the brain's healing
   resources. We'll hear the story of Dr. Albert Mason, who found he had
   super-powers, used them for good, and then lost them forever. Then,
   we'll ...

   Comments [9]
   hypnotizing cartoon

Faith Healers

   The very first placebo-controlled trial may have been the debunking of
   the charismatic Anton Mesmer (the enigmatic source responsible for the
   verb “to mesmerize”), an enlightenment figure with a healing technique
   that Ben Franklin, for one, thought was basically placebo performance.
   Historians Ed Cohen ...

   Comments [19]

Related

     * Leave a comment
     * RSS RSS Feed for Comments

Comments [43]

   Lindsay L from Oceanside, CA

   Is there a transcript available for this episode?
   Nov. 15 2013 08:56 PM
   Vote this comment up Vote this comment down Score: 0/0
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   Feature this Comment Moderate
   Laura from Indianapolis, IN

   I would be interested in someone covering the placebo effect as it
   relates to the sponge and water that seems to be a panacea for all
   ailments in international soccer games.

   I have always been amazed at the power of the sponge to immediately
   regurgitate a soccer player writhing about on the pitch.
   Sep. 03 2013 01:52 PM
   Vote this comment up Vote this comment down Score: 0/0
   Flag for moderation
   Feature this Comment Moderate
   Amanda from NYC

   Does the audio play for anyone? I can't stream it, and when I tried to
   download it, the file had zero bytes. I listened to this one a few
   years ago and wanted to re-listen.
   Aug. 21 2013 11:49 AM
   Vote this comment up Vote this comment down Score: 0/0
   Flag for moderation
   Feature this Comment Moderate
   L W Calhoun from Atlanta

   The placebo effect is a form of mind control, and as such, its effects
   can be either positive or negative. Something works because someone
   believes it works.

   Placebo is why witchcraft works. It’s real for those who believe it’s
   real.
   Jun. 26 2013 05:03 PM
   Vote this comment up Vote this comment down Score: 0/0
   Flag for moderation
   Feature this Comment Moderate
   Daniel from Jacksonville, Fl.

   I am a christian and I always find "healing" very suspicious. I do
   believe in the power of faith and I believe in the power of God. I also
   believe in a God that has the ability to heal and that perhaps people
   through faith can be healed of all kinds of illness. But to state that
   sickness is the devil living in you or that one may be sick because of
   lack of faith is unbiblical. This belief is just another silly thing
   that a small amount of christians believe but seems to get a lot of
   media attention, mainly because it is so mindless (a common theme that
   the media portrays Christians to be). We live in a world full of
   disease caused from all different things not because some one is
   possessed or the devil is attached to their spine and causes a curve. I
   would encourage people to take that segment lightly as the majority of
   Christians would not agree with what was reported on. Every church I
   have ever attended would never encourage someone to substitute medicine
   with prayer. Prayer is for faith, to grow closer to God, not to replace
   a doctor.
   Jun. 25 2013 02:19 PM
   Vote this comment up Vote this comment down Score: 0/0
   Flag for moderation
   Feature this Comment Moderate
   ted from TX

   On the placebo effect where you compared soldiers to ordinary folks.
   The soldiers were generally much younger (recruits) and have been in
   physical training for a year or two, andthey have had it drilled into
   their heads that nthey may be shot. They were conditioned fore th
   epain. On the other hand the ordinasry peoplewere probably older, not
   in great physical shape, and they were not at all perpared for being
   shot. I believe this Radio Lab story was sophomoric.
   Jun. 23 2013 09:04 PM
   Vote this comment up Vote this comment down Score: 0/0
   Flag for moderation
   Feature this Comment Moderate
   Dave Vallee from Mahanoy City

   It is troubling, and saddening to hear a religious ritual occurring in
   a medical training facility. Well, to hear it anywhere really.

   I wonder if it would have invoked comment from the producers if the
   prayers had been offered to Zeus or Thor.

   Likewise, you should have felt compelled to make some inquiry into the
   belief system of the woman who experienced the alleged faith healer.
   Yes, you were trying to maintain continuity of context, but the
   difference in how we form the stories that make possible the
   interactions of medical personnel, and those of charlatans should have
   been distinguished by your reporting. One way to have done that would
   have been to simply inquire of that woman if she wondered why Christ
   died for cures, and not for preventions. Oversight?
   Jun. 23 2013 04:26 PM
   Vote this comment up Vote this comment down Score: 0/0
   Flag for moderation
   Feature this Comment Moderate
   Candace Clemens from Arlington, MA

   Prof. Riffs - I was at a UC medical conference where an award was
   presented to the doctor whose researched proved for certain the
   efficacy of the placebo effect. This was after a doctor received an
   IgNobel award for the same conclusion. The power of the mind is the new
   frontier in science, and that is why all neurologists and psychiatrists
   need to study both. Nobody knows for sure how to distinguish between
   neurological impulses and behavioral manifestation.
   http://psychologyofpain.blogspot.com/2008/10/ig-nobel-prize-for-study-o
   n-placebo.html
   Jun. 22 2013 11:00 PM
   Vote this comment up Vote this comment down Score: 0/0
   Flag for moderation
   Feature this Comment Moderate
   alan from atlanis

   Before the library of Alexandria was burned there was just as much
   reason as when Ben Franklin started playing with kites. We just forgot.
   Check out the ancient discoveries series. there are six episodes this
   one is about robotics https://www.youtube.com/watch?v=_TFN3aAPJLU
   Jun. 22 2013 06:35 PM
   Vote this comment up Vote this comment down Score: 0/0
   Flag for moderation
   Feature this Comment Moderate
   Kristy

   RE: the doctor who lost his confidence after a respected elder
   physician told him his claim of curing the boy of his skin problem was
   impossible:

   My mother had a heart attack in 1974 and the cardiologist who treated
   her told her that she had about 10 years to live. (I found out from my
   sister after she died).

   She had a heart attack and died two days past the 10th anniversary of
   her initial heart attack. (The kind of which is routinely treated in
   emergency rooms today).

   I have long attributed this to the fact that my mother, not having
   graduated high school, put a lot of trust in people who were more
   educated than she. In effect, the doctor said she had 10 years, and she
   did as she was told.

   Regarding the warts---I know someone who, as a child, had warts and
   they disappeared after she gave them to her friend (!) as per her
   doctor's instruction. Soon her warts were gone and her friend had them!

   Jun. 21 2013 11:00 PM
   Vote this comment up Vote this comment down Score: -1/1
   Flag for moderation
   Feature this Comment Moderate
   John Parsons from Durham, NH

   During the discussion of the color of sleeping pills, it was mentioned
   that in every country in the world, blue sleeping pills work for men -
   except in Italy. The explanation was that the Italian national football
   team is called The Blues (Gli Azzurri) and that the color represented
   the excitement of a game, thus preventing sleep. The problem with that
   reasoning is that right next door, in France, the national football
   team is also called The Blues (Les Bleus), so why do the pills work
   there? The French are just as passionate about their football as the
   Italians. Somewhere there must be a different reason for the failure of
   the pills in Italian men.
   Jun. 21 2013 12:43 PM
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   Flag for moderation
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   JustSomeone JustSomeone

   I found the faith healing section very hard to listen to. I have
   scoliosis and hearing that it was "a sign of the devil" upset me to the
   point that I now avoid this episode. I don't think its bad! I
   personally just find it hard to listen to.
   May. 30 2013 12:16 PM
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   Flag for moderation
   Feature this Comment Moderate
   Lou Vignates

   Consider these terms together: "placebo effect," "spontaneous
   remission," "will to live," "expectation of getting better," and then
   consider that you don't explain anything by giving it a name.
   Aug. 27 2012 06:31 AM
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   joyce

   WISH THERE WAS A PLACEBO FOR HOT FLASHES!!!!
   Feb. 26 2012 04:06 PM
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   Kate

   harvard just started a program to research the placebo effect, website
   is www.programinplacebostudies.org
   Jan. 06 2012 11:54 AM
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   Craftylady Craftylady

   I love the fact of the history on this topic.Medical trials still go on
   today with the placebo.Are you scared or is it your belief to judge
   this episode ?
   Dec. 18 2011 12:01 AM
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   Professor Riffs

   Maybe the worst episode of Radiolab. The placebo effect is quackery
   extreme... I can see no reason to give it this much positive attention.
   Oct. 08 2011 02:44 PM
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   Aimee from Perth, Australia

   I laughed when I heard the story of the lady's faith healing: I know
   how that trick works. You can try it yourself. First, the control: form
   an "O" between you thumb and forefinger, with your wrist straight. Try
   to pull through your thumb and forfinger with the other hand - I know I
   can't. Now form the "O" with your wrist bent at 90 degrees; this time
   it's easy to pull through the thumb and forefinger.

   I'd bet a large Easter egg that that's how the faith healer did it.
   When the wrist is bent, the finger grip is significantly weaker.

   Source: Practicing Aikido regularly.
   Sep. 29 2011 05:01 AM
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   l_e_cox l_e_cox

   Finally! We sail beyond the domain of the merely scientific! This is
   the stuff leaps in knowledge are made of! But don't let anyone convince
   you that "we don't know why this works." We know plenty about why it
   works.
   Sep. 10 2011 06:20 PM
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   AHodges from Indianapolis

   The placebo affect is the only reason homeopathic hucksters can make a
   buck. They sell a "remedy" that is so diluted that it doesn't have ANY
   active ingredient. Don't get taken for a ride by these quacks. Be an
   educated and demanding consumer!
   Aug. 07 2011 11:36 PM
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   PeterAlanHOffman from wes seeya

   The part about the hypnosis reminds me of kungfu the legend continues
   where cain says something about how when the spirit is in control the
   body obeys. this is when he fell and hurt his hand and it healed
   because his mind commanded his body
   Jul. 11 2011 09:42 PM
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   David from Chicago

   Maybe there should be a follow-up given this info:

   http://www.youtube.com/watch?v=O1Q3jZw4FGs&feature=player_embedded
   Dr. Ben Goldacre does a stand-up routine about medicine, the placebo
   effect, and the mysteries of the human body at Nerdstock.
   Jan. 18 2011 02:06 PM
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   Emma

   This is so cool! I was so excited when I heard this just a couple of
   days ago. I have to do a science project for my biology class, and I
   didn't realize it but it was closely related to placebos! I'm entering
   into the science fair. Hope I get to nationals!
   Jan. 01 2011 02:30 PM
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   jeffredachmd from florida

   Another placebo effect: A study published in JAMA reported that SSRI
   antidepressants are no better than placebo for most cases of
   depression. The authors reviewed 30 years of data and concluded that
   "the benefit of antidepressant medication compared with placebo may be
   minimal or nonexistent in patients with mild or moderate symptoms". ref
   JAMA 2010;303(1):47-53)

   For more:

   http://jeffreydach.com/2010/01/21/jama-says-ssri-antidepressants-are-pl
   acebos-by-jeffrey-dach-md.aspx

   jeffrey dach md
   Dec. 28 2010 09:45 AM
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   Josh

   Here is an interesting story on NPR about placebos that work even when
   the patient knows what they are!

   http://www.npr.org/blogs/health/2010/12/23/132281484/fake-pills-can-wor
   k-even-if-patients-know-it
   Dec. 23 2010 11:18 AM
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   googie

   where can i find those picturs of the buy with the warts on his arms
   Nov. 24 2010 08:49 AM
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   nardan from USA

   I hope the story about the boy with one arm healed had been checked,
   because in another interview it was the left arm that was healed:
   "So I hypnotised him and told him that the warts would go from his left
   arm, and sent him away."
   http://www.melanie-klein-trust.org.uk/masoninterview.htm
   Oct. 26 2010 12:21 AM
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   mel from meadville, pa

   i am fairly new to radio lab, and so i will listen to the podcasts over
   and over to make sure i gather all of the information and interpret it
   well... i thought this was a wonderful "article", however i strongly
   disagree with the mention of the soldiers in the battle field and their
   way of thinking... soldiers do not think about the awards they may
   receive or the parades that may be had- they are trained to work as a
   unit and their mind set was more likely to be a thought of "someone
   else needs the morphine" or even that their body was naturally "high"
   on adrenaline with a raised level of endorphins. i relate the
   comradeship closely to mother and child. soldiers are willing to die
   for each other, much like a mother would do for her child. they bond in
   ways that are unimaginable. they are faced with a life and death
   situation and they know that the actions as a unit will win the battle,
   actions as an individual will lose the battle and likely the life of
   yourself and others.
   Sep. 14 2010 01:28 PM
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   anglafro

   The last part of the podcast mentions an old lady and her wrist
   problems. In the story, the lady said that the dude massaged her wrist.
   Not a lot of people know that massages can temporarily cure arthritis.

   the old lady was tricked...
   Aug. 04 2010 04:42 AM
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   Feature this Comment Moderate

   Bob, you said it all and effectively cut this debate short. Congrats,
   you earned an Honorable Mention at the International Contest of Compact
   Statements which Cut Discussions Short. Heh heh heh. . .
   Apr. 02 2010 11:54 AM
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   Bob Roney

   Belief may heal but ignorance kills.
   Mar. 20 2010 02:49 PM
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   Fast Eddie B. (Ed Benson)

   Just an anecdote:

   I saw a chiropractor for many, many years for low back problems. I
   would have said that the treatments seemed to work. Then I moved and
   stopped seeing a chiropractor. Now, 4 years later, I can say my back is
   better than ever, with NO manipulation.
   I had a similar experience with glucosamine - it seemed to work, but
   when I stpped taking it I could see no difference.

   Just my .02.
   Mar. 07 2010 09:16 AM
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   dddoofus

   what happened to the boy whose 1 arm was cured of Congenital
   Ichthyosiform Erythroderma? did the rest of his skin ever heal? or just
   the 1 arm? find him and do a follow up interview!
   Jan. 26 2010 10:01 PM
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   Cindy

   I found it interesting that the shaman story at the beginning of the
   show seems to contradict the conclusion of your hypnotist doctor, yet
   no mention is made of this on the show. The shaman-in-training knew he
   was a fake, and found he healed people anyway. This seems to undercut
   the medical hypnotist's opinion.
   Jan. 13 2010 06:01 PM
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   Travis

   Chris, that's a terrible story, but I think you are overreacting to
   this broadcast. Radiolab and the people they interviewed acknowledged
   the limitations of the placebo effect.

   Would you also fault them for exploring the wonders of Asprin merely
   because it can't cure cancer?
   Jan. 08 2010 11:41 AM
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   Marco Raaphorst

   again such a play with audio

   greetings from Holland
   Jan. 03 2010 09:05 AM
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   Lillian

   Somewhat new to Radiolab, I had not heard this broadcast before. I
   didn't perceive this article as being about healing per se, or as
   espousing placebo treatments in particular, but as a conversation about
   what is known, and becoming more consciously known, about one of the
   elegant complexities of the mind. And about how we experience these
   phenomena daily, moment by moment, and this knowledge is reflected
   outright in our languages and cultures to the point that it is usually
   unnoticed among what we consider the conscious, logical landscape of
   life. Thank you, Radiolab for, again, agitating the mixture so that
   intriguing bubbles may surface.
   Dec. 31 2009 04:14 AM
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   y

   Also, I've been going to PT and chiropractic for 3 months. Chiropractic
   is only half of the story. The only way to permanently change the way
   the spine is going to align is to strengthen it. A lot of doctors know
   this and will strictly not to physical therapy so that they can hold on
   to a patient longer.
   Dec. 30 2009 06:06 PM
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   y

   Chris,
   You have a great point about pseudoscience but you can't dismiss
   chiropractic medicine entirely. After a violent car accident, your
   spine can be seriously damaged. As in, the force of the wreck can cause
   muscles and bones to shift in ways that cause extreme discomfort. Also,
   some people develop scoliosis after childhood which can cause severe
   pain and discomfort.

   Some chiropractors are all too happy to crack the bones of young
   children, pregnant mothers, and those of us too weak to realize that
   we're being ripped off. It's unfortunate that the system can be abused
   for money that way.

   On the other hand, chiropractic can be extraordinarily helpful for a
   large amount of people. I hurt my back at work and was told by two
   doctors that I probably fractured or dislocated a rib. They didn't take
   X-rays but pumped me full of painkillers and anti-inflammatories. I
   went to a chiropractor based on a recommendation of a coworker. The
   doctor took an X-ray and my spine was seriously messed up. About my
   tailbone it started to curve left, then right, then at midback it
   curved left again. The curve is pinching nerves in various places,
   leaving me with really bizarre side effects.

   For example, I can now tell how crooked my back is by how often I have
   to use the restroom. I know my bladder isn't full, but the nerves from
   my spine are being affected telling my bladder that it is full
   prematurely. Sometimes I'll go every two hours! I know it isn't related
   to any other disease because I am under 25 and when I go to physical
   therapy and chiropractic like I'm supposed to, the symptoms vanish. I
   haven't had trouble with that in a while since I've strengthened by
   back into holding its shape.

   Applied properly, chiropractic can provide a wealth of relief to those
   with GENUINE problems. Any good chiropractor should have taken X-rays
   regularly on a patient being treated for a crooked spine. You can't
   tell what is going on by touch alone.

   Also, if it takes 7 years to treat back pain... Perhaps 6 years ago a
   second opinion would have been a life saver. I don't mean any offense,
   I'm just saddened that these doctors sometimes put money ahead of
   people's lives and livelihoods.
   Dec. 30 2009 06:04 PM
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   Chris Smith

   I really am disappointed. I somehow had missed this episode in when it
   was originally puked out upon us. The disservice that you do is
   amazing.

   Here is another story about who the placebo effect works. A man who
   went to a chiropractor for 7 years straight to receive some minor
   relief from the constant back pain he suffered from, was informed by
   the new owner of the practice that perhaps he should visit with a
   medical doctor. He chose to do so and after three X-rays and a CT scan,
   the cancer diagnosis that was now unstoppable was shared with him. Of
   course 7 years too late; he died and left his wife with 3 boys to
   raise.

   Belief in pseudoscience kills good people.

   These charlatans kill people. They propagate fear, they propagate
   mistrust, and you have turned around and propagated that mistrust of
   science and medicine. How many people will now not seek real treatment
   because of your lack of a proper education on the science of these
   alleged phenomena….how many will die because of your lack of
   responsibility?
   Dec. 30 2009 04:05 PM
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   Kandice Garibay

   This broadcast, for me, confirms the idea that thought holds more power
   than most people give it credit for. Just imagine how far we can go...
   Dec. 30 2009 03:11 PM
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   Wissam Dow

   Oui. I as well...
   Dec. 30 2009 03:16 AM
   Vote this comment up Vote this comment down Score: 0/0
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   Feature this Comment Moderate
   Aaron

   Oh, shucky darns. A rebroadcast. Oh well.

   I'm patiently waiting for two weeks from now. Verrrry patiently.
   Season 6 was great. I'm hoping for a great follow-up in season 7.
   Dec. 28 2009 11:44 PM
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   Photo of Ted J. Kaptchuk

Ted J. Kaptchuk

   Ted J. Kaptchuk is Professor of Medicine at Harvard Medical School and
   Director of the Program in Placebo Studies at Beth Israel Deaconess
   Medical Center in Boston. read more
   Photo of John M. Kelley

John M. Kelley

   John M. Kelley, a professor of psychology at Endicott College and an
   instructor at Harvard Medical School, is Deputy Director of the Program
   in Placebo Studies at Beth Israel Deaconess Medical Center in Boston.
   read more
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   OCT 18, 2013 1

Inside the Placebo Effect

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   BOSTON – For many medical researchers and followers of science, few
   things are more unsettling than the placebo effect. How can an inert
   sugar pill have therapeutic value?

   The answer requires understanding the context that surrounds medical
   treatment – a setting in which the symbols and rituals of health care
   combine with the charged emotional reactions that arise when patients
   encounter healers. The importance of trust, empathy, hope, fear,
   trepidation, and uncertainty in the therapeutic encounter should not be
   disregarded.

   By using sugar pills, saline injections, or even sham surgery, placebo
   research isolates provision of care from the direct effects of genuine
   medications or procedures. Recent research on the placebo effect has
   demonstrated that the clinical encounter alone – without the provision
   of any “real” medicine – can alleviate pain, improve sleep, relieve
   depression, and ameliorate the symptoms of a wide variety of
   conditions, including irritable bowel syndrome, asthma, Parkinson’s
   disease, heart ailments, and migraine.

   Placebos mainly influence patient self-appraisal. They cannot shrink
   tumors; but they can help patients experience less of the fatigue,
   nausea, pain, and anxiety that are associated with cancer and its
   treatment. They cannot lower cholesterol or reduce high blood pressure,
   but they may alter mood or pain sufficiently to promote more healthful
   behaviors.

   Placebos can behave like drugs; and the placebo effect can also make
   drugs more effective.

   Research shows that various components of the placebo effect – for
   example, the paraphernalia of care (pills and syringes) and the
   patient-provider relationship – can be added incrementally in a manner
   analogous to dose dependence (the higher the dose, the greater the
   effect).

   Indeed, these components have been shown to boost the efficacy of many
   powerful medications.

   For example, when morphine is administered by injection in full view of
   the patient, it is significantly stronger than when it is given through
   an intravenous line without the patient’s knowledge.

   Many psychosocial mechanisms have been implicated in placebo responses.
   Increased hope, positive expectations, and reduced anxiety can all
   modify “mindsets” that guide how patients respond to noxious
   sensations. Evidence strongly suggests that the support and empathy of
   a thoughtful and attentive physician can improve clinical outcomes.
   Indeed, it has been demonstrated that non-conscious environmental cues
   and symbols – the white coat or the diploma on the wall – can “prime” a
   patient to experience improvement.

   Until recently, it was assumed that the effects of placebo pills
   depended on concealment or deception. The patient had to believe that
   the treatment was “real” for placebos to work. But new research
   indicates the potential for significant clinical improvement even if
   patients are told that they are ingesting an inactive substance. This
   suggests that the simple enactment of a treatment ritual may, like
   conscious expectations, have a powerful impact.

   In fact, the power of imagination, it seems, has a basis in
   neurobiology. Recent evidence shows that when placebos have salubrious
   effects, they engage the same neurological pathways as active
   medications. For example, when patients experience pain relief from
   placebos, the brain releases endogenous opioids and/or CB1 cannabinoids
   – the very same mechanisms that mediate pain relief derived from
   pharmaceutical treatments.

   Likewise, neuroimaging studies show that placebo treatment activates
   specific brain structures such as the prefrontal cortex and the rostral
   anterior cingulate cortex. Experiments on patients with Parkinson’s
   disease have shown that placebo treatment releases endogenous dopamine
   in the striatum region of the brain. Moreover, intriguing pilot
   research suggests that there may be genetic factors that predispose one
   to have greater placebo responses.

   The effects of placebos are not always beneficial. The placebo effect
   has a dark twin called the nocebo effect. Although placebos are
   biologically inert, as many as 26% of placebo-treated patients drop out
   of clinical trials after suffering intolerable side effects, which are
   usually the same as the possible side effects of the drug being tested.
   For example, in a trial of anti-migraine medication, if the active
   ingredient is an anticonvulsant, the nocebo effect (the placebo’s side
   effect) will disproportionally relate to anorexia or memory; but if the
   active ingredient is a non-steroidal anti-inflammatory drug, the nocebo
   effect will more likely be gastrointestinal symptoms and thirst.

   This underscores the importance of placebo effects in the development
   of new drugs. To approve new pharmaceuticals, the US Food and Drug
   Administration requires two well-designed randomized controlled trials
   in which the drug demonstrates superiority over placebo treatment.

   However, evidence suggests that for some illnesses, placebo effects
   have grown progressively larger over the last several decades. This
   “placebo drift” poses significant challenges to detecting drug-placebo
   differences.

   And that highlights a more fundamental point: In our rush to embrace
   high-tech medicine, we tend to forget the enormous potential for
   healing that can arise from a good therapeutic relationship. Placebo
   research has demonstrated that the context within which treatment takes
   place and the patient-clinician relationship have huge potential to
   improve health outcomes.

   We need to learn more about the placebo effect’s power and limitations.
   We also need to learn how to translate this scientific knowledge into
   ethical and effective methods that physicians can use to improve
   medical outcomes. And we need to know more about the placebo effect in
   clinical trials. In short, we need to stop thinking in terms of the
   “art of medicine” and start exploring a new science of healing.
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CommentedZsolt Hermann NOV 7, 2013
       Thank you for this intriguing article. I agree with everything the
       article describes, as a surgeon myself, and I am sure other health
       professionals can testify "intrinsic" factors are crucial, we could
       even say most important in healing, acquiring illness and health in
       general. I would suggest that while modern medicine looks at
       illness and healing as an external process, illness happening due
       to external causes, pathogens, environmental factors, and healing
       also have to come "from the outside" from overwhelming
       pharmaceutical agents, improving technology and surgical miracles
       and of course expensive implants, true illness/healing is a
       completely internal matter. Although Indian or Chinese traditional
       medicine has several thousands of years experience with this
       viewpoint, by today even in their original countries very few
       people remember, let alone practice this notion. All medicine
       should be doing is facilitating, initiating a healthy protective,
       healing response from the body and the body then heals itself. And
       beyond medicine the whole human environment should function in such
       natural, self supporting way as any other interconnected natural,
       living system providing healthy, sustainable living, strong inner
       protection to all the individuals and the whole.

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   1. placebo effect
   This is mind over matter; when somebody believes that something will
   happen to his health, it does even when it wouldn't have otherwise.
   This generally happens when doctors tell patients that their health
   will improve even though there's no logical reason to believe that; the
   patients' optimism then helps heal them.
   The doctor gave Jimmy sugar capsules and told them it would cure his
   headaches; it did even though the capsules didn't do anything. Classic
   placebo effect!
   mark as favorite buy placebo effect mugs & shirts
   mind over matter illogical doctor medicine psychology
   by iLikeSoup February 17, 2010 add a video add an image
   Random Word
   2. placebo effect
   When you are with people who are doing something, even when you arent
   doing it, you feel the same effect. It works depending on if you
   mentally believe in it or not.
   Since I'm straight edge, when my friends drink, i use the placebo
   effect and feel the same as they do.
   mark as favorite buy placebo effect mugs & shirts
   straight edge triple x bud bong piece
   by taaaaayyyyllooorrrr January 11, 2009 add a video add an image
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Putting the placebo effect to work

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   Rather than dismiss it, we should try to understand the placebo effect
   and harness it when we can.

   For a long time, the placebo effect was held in low regard. If people
   responded to a suspect treatment, we said it was "just the placebo
   effect." The suggestion was that they had been fooled in some way, and
   their response was inauthentic.

   But attitudes are shifting, even in conventional medical circles.
   Randomized trials, some of them led by researchers at the Harvard-wide
   Program in Placebo Studies and the Therapeutic Encounter, have deepened
   the understanding of the placebo effect and its various components.
   Researchers have also used brain scans and other technologies to show
   that there may be a physiological explanation for the placebo effect in
   many cases. There is some danger that uncritical acceptance of the
   placebo effect could be used to justify useless treatments. But more
   important is the growing recognition that what we call the placebo
   effect may involve changes in brain chemistry — and that the placebo
   effect may be an integral part of good medical care and an ally that
   should be embraced by doctors and patients alike.

The power of expectation

   Arriving at a tidy definition of the placebo effect is difficult, but
   here's a try: it's a favorable response to a medical intervention — a
   pill, a procedure, a counseling session, you name it — that doesn't
   have a direct physiological effect. (Note the emphasis on direct,
   because there do seem to be indirect effects.) The classic example is
   when people enrolled in a study experience some improvement in their
   condition even though they have been assigned, for comparison purposes,
   to take "dummy" pills that don't contain any active ingredients.

   Expectations appear to have a lot to do with the effect. If an
   intervention is believed to help a condition, a certain percentage of
   people who receive it will experience some benefit. How large a
   percentage varies tremendously and depends on the condition, the
   strength of belief, the subjectivity of the response, and many other
   factors. The placebo effect may also have an element of psychological
   conditioning: once someone benefits from an intervention, the person
   starts to associate that intervention with a benefit. The association,
   and therefore the benefit, may get stronger with additional exposures
   to the intervention.

An effect of care that's caring

   There's also evidence that some of the placebo effect is a favorable
   reaction to care and attention from people who patients believe can
   help ease their suffering and distress. Researchers associated with
   Harvard's placebo studies program published a study in 2008 that
   illustrates this aspect of the response very nicely. The volunteers for
   the study were people with irritable bowel syndrome (IBS), a condition
   that causes abdominal pain and changes in bowel movements in the
   absence of any discernible changes to the bowel. The placebo treatment
   was sham acupuncture, which involves the use of needles that,
   unbeknownst to the patient, retract into their handles instead of
   penetrating the skin. The placebo effect of the sham acupuncture
   needles was impressive: 44% of those treated with just the sham needles
   reported relief from their IBS problems. When sham acupuncture was
   combined with attentive, empathetic interaction with the acupuncturist,
   the placebo effect got even larger, with 62% reporting relief from
   their IBS woes.

Subjective vs. objective

   The placebo effect is most pronounced and relevant when a treatment's
   success or failure depends largely on the subjective experiences of
   patients. That's often the case for conditions that are defined mainly
   by symptoms, such as depression, and problems like migraine headaches
   and back pain that are defined primarily by the pain they produce.

   Sometimes treatments can be judged by both objective and subjective
   outcomes, and a Harvard study published in 2011 in The New England
   Journal of Medicine showed that the placebo effect may influence one
   and not the other. This small study compared the response of 39 people
   with asthma to albuterol, an inhaled bronchodilator that's commonly
   used to treat asthma, with two different inactive treatments, a placebo
   inhaler and sham acupuncture. Albuterol was much more effective than
   both the placebo inhaler and the sham acupuncture when an objective
   test of lung function, called FEV1, was used to measure the response of
   the asthmatic study volunteers. But when the study volunteers were
   asked about their symptoms and perceived improvement in their asthma,
   albuterol and the placebos performed equally well.

   Research is showing that the placebo effect often seems to be
   associated with objective changes in brain chemistry. A number of
   studies have shown, for example, that the brain releases natural
   pain-relieving substances, called endorphins, when people enrolled in
   pain studies are given placebos. Research results indicate that
   measurable changes in brain chemistry may explain the large placebo
   effect seen in depression treatment. Parkinson's disease is associated
   with a shortage of a brain chemical called dopamine, and in studies of
   the disease, placebos have increased the production of dopamine.

Getting it out in the open

   In 2008, just under 700 American internists and rheumatologists were
   surveyed about prescribing placebos. Only a small percentage had ever
   prescribed "pure" placebos like sugar pills or saline solutions. But
   about 40% reported that they had prescribed over-the-counter pain
   relievers or vitamins as placebos, not because they believed these
   compounds would have a direct effect on the person's condition. Even if
   patients feel better, prescribing pain relievers and vitamins in that
   way involves some deception.

   Dr. Ted Kaptchuk, director of the Harvard placebo program, and
   colleagues have conducted "open-label" placebo studies, in which
   patients were told they were taking a placebo and that the placebo
   effect is powerful. In one small study of IBS patients, Dr. Kaptchuk
   and his colleagues found that an open-label placebo still produced a
   placebo effect and was about 20% more effective than no treatment.
   These and other results suggest that doctors could be more up-front
   with patients, informing them that a prescription is mainly for placebo
   purposes, and their patients would still benefit, as long as the
   prescription had no major drawbacks.

What you can do

   We're a long way from fully understanding the placebo effect. But here
   are some things you can do (and think), based on what researchers have
   discovered so far:

   Make sure you're getting the support you need from your doctor. Placebo
   effect research has shown how important a supportive doctor-patient
   relationship can be. If you're not getting the support and attention
   you need, consider switching doctors.

   Recognize that it might be "in your head" — but there's nothing wrong
   with that. Behind the subjective experience of feeling better (and
   worse) are objective changes in brain chemistry that we've only started
   to understand.

   Find treatments you can believe in… Expectations that an intervention
   will have some benefit increase the chances that it will.

   …but keep your healthy skepticism. Quacks and charlatans can exploit
   the placebo effect to peddle treatments that are useless, and even
   harmful, if for no other reason than they keep people from getting
   treatment that is directly effective.
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   19 March 2002, Vol 136, No. 6
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     * PDF

   Ideas and Opinions

   Published online 19 March 2002

   Deconstructing the Placebo Effect and Finding the Meaning Response
   Daniel E. Moerman, PhD; Wayne B. Jonas, MD
   [+-] Author Affiliations

   From University of Michigan, Dearborn, Michigan; and Samueli Institute
   and Uniformed Services University of the Health Sciences, Bethesda,
   Maryland.

   Grant Support: In part by a grant from the National Science Foundation
   to Dr. Moerman (NSF SBR-9421128).

   Requests for Single Reprints: Daniel E. Moerman, PhD, Department of
   Anthropology, University of Michigan–Dearborn, 6515 Cherry Hill Road,
   Ypsilanti, MI 48198; e-mail, dmoerman@umich.edu.

   Current Author Addresses: Dr. Moerman: Department of Anthropology,
   University of Michigan–Dearborn, 6515 Cherry Hill Road, Ypsilanti, MI
   48198.

   Dr. Jonas: Department of Family Medicine, Uniformed Services University
   of the Health Sciences, Bethesda MD 20814.
   More Author Information
   Ann Intern Med. 19 March 2002,136(6):471-476
   doi:10.7326/0003-4819-136-6-200203190-00011
   [+-] More
   Article
   Comments (0)

   We provide a new perspective with which to understand what for a half
   century has been known as the “placebo effect.” We argue that, as
   currently used, the concept includes much that has nothing to do with
   placebos, confusing the most interesting and important aspects of the
   phenomenon. We propose a new way to understand those aspects of medical
   care, plus a broad range of additional human experiences, by focusing
   on the idea of “meaning,” to which people, when they are sick,
   often respond. We review several of the many areas in medicine in which
   meaning affects illness or healing and introduce the idea of the
   “meaning response.” We suggest that use of this formulation, rather
   than the fixation on inert placebos, will probably lead to far greater
   insight into how treatment works and perhaps to real improvements in
   human well-being.

Topics

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Placebo Effect and Lessons for the Physician-Patient Relationship

   Sep. 19, 2013 &#151; The findings of a comprehensive review of the
   placebo phenomenon and its consequences for clinical medicine are
   contained in a new article, "Placebo and the New Physiology of the
   Doctor-Patient Relationship," published in Physiological Reviews. The
   effort, undertaken by physician-researcher Fabrizio Benedetti of the
   Department of Neuroscience, University of Turin Medical School, and
   National Institute of Neuroscience, Turin, Italy, provides an in-depth
   biological and evolutionary approach to examining the placebo effect in
   relationship to the doctor-patient relationship.
     __________________________________________________________________

   Share This:

   Placebo, in Latin, means "I shall please," and its role in research and
   medicine is a fascinating story. One of the first recorded use of
   placebos involved Benjamin Franklin who was commissioned by the French
   king Louis XVI to test the effectiveness of mesmerism, a kind of
   healing practice which was supposed to act through a healing fluid
   released from the healer. Franklin's team utilized blind assessments
   and placebo interventions to women patients and determined that their
   improvements were spurred on by the imagination. Over time there was
   awareness to both researchers and physicians that clinical trials were
   susceptible to imagination and biases. This led to the use of the
   double-blind design, in which neither the investigator nor the patient
   knew the nature of the tested therapy (it could be either real or
   fake).

   For many years placebos have been used for the validation of therapies,
   but they have also traditionally taken as an example of the powerful
   interaction between mind and body with associated commentary research
   appearing in psychology literature. Dr. Benedetti's research is aligned
   with the current state of placebo research, a complex field of
   investigation which ranges from psychology to psychophysiology, from
   pharmacology to neurophysiology, and from cellular/molecular analysis
   to modern neuroimaging techniques.

   Dr. Benedetti's research methodology employed in this article
   transcends the traditional division between psychology, the study of
   the mind and how it works, and biology, the study of all living things.
   This article clarifies the research conducted to identify the
   relationship between pharmacological treatments administered to the
   patient and the role of the mind in the overall patient health. In
   addition, it clarifies the interaction between psychological processes
   and the many physiological functions of the human body.

   This new discipline acknowledges that placebos and placebo responses
   with their wide range of physiological responses involving numerous
   mechanisms across a number of conditions, systems, and interventions
   represent an active field of neurobiological research. With that, Dr.
   Benedetti, using biochemical, cellular and physiological tools, aptly
   summarizes research new findings on describing the placebo effect on
   psychology and biology and their impact on the doctor-patient
   relationship. Among the issues discussed in detail are:

   o There is no one "the placebo effect." There are different mechanisms
   in play across a variety of medical conditions and therapeutic
   interventions. For example, a placebo effect takes place because there
   is expectation. The patient expects a therapeutic benefit, and this
   kind of expectation actually has an effect on the brain and the body.

   o The connection between expectation and real improvement that may
   occur is due at least to two mechanisms. The first may be a reduction
   of anxiety. The second is between expectation and the activation of a
   reward mechanism by the region of the brain known as the nucleus
   accumbens (which also governs pleasure, reinforcement learning,
   laughter, addiction, aggression, fear, impulsivity and the placebo
   effect.)

   o When a treatment is given to a patient, be it a placebo or real, it
   is administered in a complex set of psychological states that vary from
   patient to patient and from situation to situation. For example, when a
   placebo is given to relieve pain, it is administered along with stimuli
   which tell the patient that a clinical improvement should be occurring
   shortly. These stimuli can include the color and shape of the pill,
   patient and provider characteristics and the healthcare setting.

   o Recent research has revealed a reduced efficacy of drugs when they
   are administered covertly to the patient. In fact, if the
   placebo/expectation component of a treatment is eliminated by means of
   a hidden administration (unbeknownst to the patient), the psychological
   component of the therapy is absent as well.

   For physicians, psychologists, and health professionals these and other
   recent findings found in Dr. Benedetti's article can foster enhanced
   understanding of how their words, attitudes, and behaviors impact on
   the physiological profile of their patients' brains. This "direct
   vision" of the patient's brain will hopefully boost health
   professionals' empathic, humane, and compassionate behavior further.
   Moreover, understanding the physiological underpinnings of the
   doctor-patient relationship will lead to better medical practice as
   well as to better social/communication skills and health policy.
   Share this story on Facebook, Twitter, and Google:

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     __________________________________________________________________

   Story Source:

     The above story is based on materials provided by American
     Physiological Society (APS).

     Note: Materials may be edited for content and length. For further
     information, please contact the source cited above.
     __________________________________________________________________

   Journal Reference:
    1. Fabrizio Benedetti. PLACEBO AND THE NEW PHYSIOLOGY OF THE
       DOCTOR-PATIENT RELATIONSHIP. Physiological Reviews, September 2013
       DOI: 10.%u200B1152/%u200Bphysrev.%u200B00043.%u200B2012

   Need to cite this story in your essay, paper, or report? Use one of the
   following formats:
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Placebo Effect Produces Higher Test Scores

   A new study finds it’s possible to trick people into doing better on a
   general-knowledge exam.

   [pills.jpg]
   (PHOTO: TRIFF/SHUTTERSTOCK)
   March 24, 2013 • By Tom Jacobs •
   725 Flares Filament.io 725 Flares ×

   Scientists are increasingly convinced of the power of the placebo
   effect. Believing that one is receiving treatment when you're not—say,
   in the form of a pill that supposedly contains a powerful drug that is
   actually just sugar—can produce surprisingly strong results, at least
   for some patients, some of the time.

   Newly published research suggests a placebo process can produce a
   similarly positive outcome for test-takers. In short, the belief that
   you have access to the answers makes it more likely you will get them
   right.

   “People have powerful psychological resources to deal with challenges,
   but those resources cannot always be used deliberately,” German
   psychologist Ulrich Weger and Australian psychologist Stephen Loughnan
   write in the Quarterly Journal of Experimental Psychology. Just as a
   dummy pill can help people access their ability to tolerate pain, they
   report, a false conviction can help test-takers relax and improve their
   performance.

   Their experiment featured 40 undergraduates, each of whom took a
   20-question general-knowledge text. Questions ranged from the numerical
   value of pi to the artist who created Guernica; participants were given
   four possible answers and instructed to pick the correct one.

   Before doing so, half the students were told that just before each
   question was asked, the correct answer was momentarily flashed onto the
   screen. They were informed that this happened too quickly for them to
   process the information consciously, but assured that it would register
   in their brains.

   A “demonstration” showed them the process in slow motion, reinforcing
   their belief that this was really happening. In fact, the researchers
   write, “the subliminally presented answers of this experimental phase
   were random letter strings.”

   No matter: “Participants in the placebo condition who believed they had
   been exposed to the correct answers subliminally scored higher than
   participants in the control condition,” Weger and Loughnan write.

   The researchers suspect the false assurance produced  “a weakening of
   inhibitory mechanisms that normally impair performance on a task.” In
   other words, the participants’ belief that they had the answers allowed
   them to relax, focus—and answer more questions correctly.

   When you’re confident, “anxieties that have previously taxed cognitive
   resources … become available for other tasks and processes,” they
   write.

   Weger and Loughnan concede this is one small study, but it conforms
   with earlier research on confirmation bias and self-fulfilling
   prophecies. In this case, they note, the positive bias was not the
   product of internal self-talk, but rather an outside intervention—a
   mental sugar pill.

   As such, they speculate, this technique could come in handy in
   situations “where a participant’s genuine skills profile needs to be
   assessed, uncontaminated by the impact of self-incapacitating fears.”
   Did that job applicant’s low score reflect a lack of brainpower, or
   merely the anxiety of an inherently stressful situation? Some version
   of this experiment could be a fine way way to find out.

   For the rest of us, this study confirms that the best possible mantra
   to use before taking a test is: You know this.

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   About Tom Jacobs

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   experience at daily newspapers. He has served as a staff writer for The
   Los Angeles Daily News and the Santa Barbara News-Press. His work has
   also appeared in The Los Angeles Times, Chicago Tribune and Ventura
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Welcome to PiPS

   For many years, the placebo effect was considered to be no more than a
   nuisance variable that needed to be controlled in clinical trials. Only
   recently have researchers redefined it as the key to understanding the
   healing that arises from medical ritual, the context of treatment, the
   patient-provider relationship and the power of imagination, trust and
   hope.

   Although our biomedical health care system often considers these
   humanistic dimensions of care as secondary to the administration of
   pharmaceuticals and procedures, the emerging field of placebo studies
   is producing scientific evidence that these more intangible elements of
   medicine may fundamentally contribute to the improvement of patient
   outcomes.

   The Program in Placebo Studies and the Therapeutic Encounter hosted at
   Beth Israel Deaconess Medical Center is the first research center to
   pursue placebo studies through interdisciplinary, translational
   research initiatives that bridge the basic, clinical and social
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   methodologies as they design studies that elucidate critical aspects of
   placebo studies.  Read more…

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   Karin at work PiPS seeks to establish itself as a center where young
   researchers can develop careers in placebo studies. Collaborations
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     * Special article

The placebo effect

    1. Sundararajan Rajagopal, Consultant Psychiatrist

    1.


    South London and Maudsley NHS Trust, Adamson Centre for Mental
    Health, St Thomas’ Hospital, London SE17EH, e-mail:
    Sundararajan.Rajagopal{at}slam.nhs.uk

     * Declaration of interest
     * None.


   Next Section

   The placebo effect is a fascinating phenomenon in clinical practice.
   Studies have shown that there is a significant placebo effect in a wide
   range of medical conditions including psychiatric disorders. This
   article looks at the background of the placebo effect, defines the
   common terms used, describes the various hypotheses that have been put
   forward to explain this seemingly inexplicable phenomenon and also
   covers the issue of using placebos in research trials, highlighting the
   important ethical dilemmas involved. Throughout, specific emphasis is
   given to psychiatry.
   Previous SectionNext Section

Background

   The term placebo is derived from the Latin verb ‘placare’, ‘ to
   please’. The American anaesthetist Henry K. Beecher (1955) coined the
   term ‘ placebo effect’. He reported that, on average, about a third of
   patients with a range of conditions improved when they were given
   placebos. This subsequently led to the development of
   placebo-controlled trials, whereby a new drug is said to have
   significant benefit only if it shows superiority over placebo. The
   placebo effect has also been a source of recent interesting debate in
   psychiatry with some claiming that a considerable proportion of benefit
   from antidepressant medication derives from the placebo effect (Kirsch
   & Sapirstein, 1998), whereas others (Leutcher et al, 2002) have
   stressed that response to placebo and to antidepressants involves
   distinct biological mechanisms.
   Previous SectionNext Section

Definitions

   In general, a placebo is an inert substance that has no inherent
   pharmacological activity. It looks, smells and tastes like the active
   drug with which it is compared. An ‘active placebo’ is one that has its
   own inherent effects but none for the condition that it is being given
   for (e.g. use of atropine as the control drug in trials of tricyclic
   antidepressants). A placebo need not always be pharmacological. It
   could be procedural, for example, sham electroconvulsive therapy (ECT),
   where the patient is anaesthetised but not given ECT. Surgical placebo
   is a procedure where the patient is anaesthetised and superficial
   procedures (e.g. skin incision, burr hole) are performed without the
   actual surgery.

   Placebo equivalents are also employed in complementary medicine. For
   example, sham acupuncture consists of needles placed at non-acupuncture
   points. A recent study (Linde et al, 2005) showed that real acupuncture
   was no more effective than sham acupuncture in reducing migraine
   headaches, although both interventions produced benefits compared with
   a waiting list control.
   Previous SectionNext Section

Why does the placebo effect occur?

Natural remission theory

   This states that the improvement that occurs with the administration of
   placebo is coincidental and would have occurred even without it. This
   theory explains the beneficial effects of placebo in short-lived
   conditions like common cold, headache, etc, but does not satisfactorily
   explain why even patients with chronic conditions such as hypertension
   or schizophrenia show improvement with placebo.

   An allied hypothesis is the ‘regression to the mean’ theory. Regression
   to the mean is a statistical concept; according to this, if an initial
   test result is extreme and if the test is repeated, statistically there
   is a greater likelihood for the second result to be closer to the mean
   than for it to be more extreme than the first result. Usually only
   patients who are significantly unwell (e.g. depression score above a
   certain cut-off point) are eligible to enter a trial. Hence, at
   follow-up they are more likely to show an improvement (depression score
   being closer to the mean than the first score) than a deterioration,
   owing to regression to the mean (McDonald et al, 1983).

Classical (Pavlovian) conditioning

   In the original experiment of Pavlov, the dog salivated at the sound of
   the bell even without any food, as it had previously been conditioned
   to expect food by pairing the bell with food. Food is the unconditioned
   stimulus, salivation owing to food is the unconditioned response; the
   bell is the conditioned stimulus and salivation owing to the bell is
   the conditioned response.

   In a similar manner, patients who have had past experience of getting
   better with active medication may be conditioned to anticipate
   improvement by any subsequent prescription, including placebo. Using
   the classical conditioning analogy, the active medication is the
   unconditioned stimulus, improvement owing to active medication is the
   unconditioned response, the placebo is the conditioned stimulus, and
   improvement owing to placebo is the conditioned response.

Other psychological factors

   Patient expectations are important in determining the placebo effect.
   Treatments that are perceived as being more powerful tend to have a
   stronger placebo effect than those that are perceived to be less so.
   Thus, placebo injections have more effect than oral placebos, capsules
   are perceived as being stronger than tablets, bright-coloured placebos
   are more effective than light-coloured ones larger placebos have more
   effect than smaller ones, and two placebos have more effect than one.
   Also, the status of the treating professional is directly related to
   the placebo effect. The same compound has been found to be more
   powerful if it is branded than when it is unbranded (Branthwaite &
   Cooper, 1981).

   In a novel study, Benedetti et al (2003) examined the impact of the
   patient’s awareness that they are having a certain treatment
   administered/withdrawn on the outcome. They studied three treatments in
   three groups of patients - intravenous morphine for post-thoracotomy
   pain, intravenous diazepam for post-thoracotomy anxiety and stimulation
   of the subthalamic nucleus for idiopathic Parkinson’s disease. In each
   group, some patients were informed of the fact that they were receiving
   the treatment (e.g. by a doctor administering the injection) but others
   were not aware as they received an infusion from an automatic
   pre-programmed machine. In all the groups, the efficacy of the
   respective interventions was greater when the patient was aware of the
   procedure than when they were not. Similarly, being aware that a
   treatment was being withdrawn worsened the symptoms much more than when
   the treatment was withdrawn without the patient’s knowledge. From a
   psychiatric point of view, neither the hidden administration nor hidden
   withdrawal of diazepam had any significant positive or negative effect
   respectively but the open administration of diazepam improved anxiety
   symptoms and open withdrawal worsened them.

Role of endogenous opioids

   In a systematic review, ter Riet et al (1998) concluded that endogenous
   opioids (e.g. endorphins) play a significant role in mediating
   placebo-induced analgesia. Previous studies had shown that
   placebo-induced analgesia is partially reversed by administering the
   opioid antagonist naloxone (Grevert et al, 1983). There is also growing
   interest in the role of neurotransmitters, particularly dopamine, in
   placebo effects on mood and behaviour.
   Previous SectionNext Section

Pattern of placebo improvement

   Among psychiatric disorders, the placebo effect has been most
   extensively studied in depression. ‘Pattern analyses’ have shown that
   the improvement as a result of placebo in depression tends to be
   abrupt, occurs early in treatment and is less likely to persist
   (Quitkin et al, 1991), whereas improvement in response to
   antidepressants tends to be gradual, occurs later and is more likely to
   persist. Even among patients apparently responding to the active drug,
   if the pattern of improvement is consistent with a placebo response
   (i.e. abrupt and early), the improvement tends to be short-lived.

   Stewart et al (1998) investigated whether they could predict relapse of
   depression from the initial pattern of response. Patients who had
   responded to treatment with fluoxetine for 12–14 weeks were then
   randomly allocated to continuation/maintenance treatment for 50 weeks
   with either placebo or fluoxetine. Those patients who had shown a
   placebo pattern of improvement during the initial fluoxetine phase
   relapsed in a similar manner whether they continued on fluoxetine or
   were switched to placebo, but patients who had shown a true drug
   pattern of improvement relapsed more if they were switched to placebo
   in the maintenance phase. This study adds strength to the hypothesis
   that, even among drug responders, only a certain proportion will
   benefit from maintenance treatment.

   Hrobjartsson & Gotzsche (2001) conducted a major systematic review of
   placebo-controlled trials involving 40 clinical conditions, including
   hypertension, asthma, pain, depression, schizophrenia, anxiety and
   epilepsy. They concluded that placebos tended to have no significant
   effects on binary outcomes, and possibly had small beneficial effects
   on continuous subjective outcomes and in the treatment of pain.
   Previous SectionNext Section

Use of placebos in clinical trials

   It is generally accepted that a double-blind randomised controlled
   trial (RCT) is the best research method to study the efficacy of
   clinical interventions.

   However, the use of placebos for conditions for which effective
   treatments are already available raises an important ethical question.
   Should a new treatment be compared with an established treatment or
   should it only have to demonstrate superiority over placebo in order to
   be accepted as another effective treatment? Rothman & Michels (1994)
   have criticised the use of placebo-controlled trials to test new drugs
   for conditions with potentially irreversible consequences, such as
   onchocerciasis and rheumatoid arthritis, when established treatments
   for these conditions already exist.

   Death by suicide is associated with major psychiatric disorders such as
   depression, and the use of placebo-controlled trials to test the
   efficacy of new drugs is fraught with ethical issues.

   Another important question involves the masking of the double-blind
   trials. Margraf et al (1991) reported that a majority of patients in a
   double-blind study of alprazolam v. imipramine v. placebo could
   correctly guess whether they were on an active drug or placebo. In
   addition, the ‘masked’ assessors were even able to distinguish between
   the two active drugs.

   Informed consent entails the patients being made aware that they will
   be receiving either an active drug or placebo. Therefore, it may not
   require more than just monitoring one’s side-effects closely to
   accurately determine whether one is on active medication or placebo.

   In addition to ethical issues, RCTs with a placebo control group have
   other limitations. RCTs only demonstrate statistical significance. If
   the sample size is very large, even if the difference in clinical
   outcome between the two groups is small and clinically insignificant,
   it may be detected as being significant by the statistical test.

   In any RCT, the placebo is made by the manufacturer of the active drug.
   Hence, placebos used in one study will be different in form (size,
   shape, tablet/capsule, etc.) from those used in another study,
   depending on the form of the active drug. This may account for the wide
   variation in placebo response observed for the same condition.
   Previous SectionNext Section

Side-effects of placebos

   When a placebo produces prominent side-effects it is known as a ‘
   nocebo’. The term ‘nocebo effect’ encompasses the negative consequences
   resulting from the administration of a placebo. In placebo-controlled
   studies of psychotropic drugs, the placebos tend to cause a similar
   range of side-effects as the active drugs but usually with a much lower
   incidence rate. Non-specific side-effects, such as headache and nausea,
   tend to be more common than more specific ones such as acute dystonia
   or QT prolongation. ‘Placebo sag’ refers to the attenuation of the
   placebo effect with repeated use (Peck & Coleman, 1991). There are
   historical reports of placebo dependence (Vinar, 1969).

   The nocebo effect clearly illustrates the role of patient expectations
   in perceived side-effects. Usually patients included in trials of
   psychotropic medication have already received previous treatment with
   active medication in the past, as most major psychiatric disorders tend
   to follow a chronic course. Hence, even if they are given placebo this
   time, they may anticipate side-effects similar to those that they
   experienced when they were receiving treatment with the active drug.
   Also, patients may be influenced by the list of side-effects
   experienced by their friends or relatives who have received such
   treatment in the past, and by the list of potential side-effects
   described by the researchers before obtaining informed consent.

   Just as doubts have been cast on the beneficial effects of the placebo,
   so have questions been raised about the nocebo effect. Even healthy
   people who are not taking any medication have been shown to have a high
   prevalence of a range of symptoms which are similar to the side-effects
   investigated during RCTs. Thus, side-effects reported by patients on
   placebo may be a reflection of pre-existing or spontaneously occurring
   symptoms rather than being placebo-induced. Similarly, RCTs may be
   overestimating the side-effects (especially the nonspecific ones) of
   active drugs.

   However, the nocebo effect is not purely psychological. It has been
   shown that nocebo hyperalgesia (i.e. an increase in pain as a result of
   placebo) is mediated by cholecystokinin and is abolished by the
   cholecystokinin antagonist proglumide (Benedetti et al, 1997). In a
   systematic review of double-blind RCTs comparing fluoxetine and
   placebo, Casper et al (2001) found similar rates of placebo response in
   men and women but slightly more nocebo effects in women.
   Previous SectionNext Section

Conclusions

   Despite half a century having passed since its inclusion in modern
   medicine, the placebo effect is still poorly understood. Beecher’s
   (1955) original study, which showed an overall average placebo response
   of 35%, has been strongly criticised for major methodological
   shortcomings (Kienle & Kiene, 1997).

   All discussion regarding placebos is based on the assumption that they
   are inert. But are they really so? Placebos are generally referred to
   as ‘ sugar pills’; sugar is not chemically inert. Similarly, the tablet
   coating or the capsule covering are not inert. Hence, the possibility
   that the ‘inert’ chemical in the placebo may be relevant to the
   condition being studied should not be dismissed.

   Whatever the reasons for the placebo effect, the most important message
   for clinicians is that just because someone responds to a placebo does
   not mean that the initial ailment for which they sought help was false.
     * © 2006 Royal College of Psychiatrists

   Previous Section

References

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       BEECHER, H. K. (1955) The powerful placebo. JAMA, 159, 1602 -1606.
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       KIRSCH, I. & SAPIRSTEIN, G. (1998) Listening to Prozac but hearing
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   10. LEUCHTER, A.F., COOK, I.A., WITTE, E. A., et al (2002) Changes in
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       McDONALD, C. J., MAZZUCA, S. A. & McCABE, G. P., Jr (1983) How much
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       PECK, C. & COLEMAN, G. (1991) Implications of placebo theory for
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       QUITKIN, F. M., RABKIN, J. G., STEWART, J.W., et al (1991)
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       STEWART, J.W., QUITKIN, F. M., McGRATH, P. J. (1998) Use of pattern
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   19. ↵
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       Abstract/FREE Full Text

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    2. Background
    3. Definitions
    4. Why does the placebo effect occur?
    5. Pattern of placebo improvement
    6. Use of placebos in clinical trials
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    8. Conclusions
    9. References

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The golden arse beam method.

   July 9th, 2011 by Ben Goldacre in alternative medicine, irrationality
   research, placebo | 15 Comments »

   Ben Goldacre, The Guardian, Saturday 9 July 2011

   Since I was a teenager, whenever I have a pivotal life event coming –
   an exam, or an interview – I perform a ritual. I sit cross-legged on
   the floor, and I imagine an enormous golden beam of energy coming out
   of my arse. Read the rest of this entry »

Placebo! Nocebo!

   April 17th, 2010 by Ben Goldacre in onanism, placebo, podcast | 29
   Comments »

   Hi, two quick videos… one on the mighty placebo effect, via NHS
   Choices, one on the nocebo effect from Nerdstock. Read the rest of this
   entry »

All bow before the mighty power of the nocebo effect

   November 28th, 2009 by Ben Goldacre in homeopathy, placebo | 70
   Comments »

   Ben Goldacre, Saturday 28 November 2009, The Guardian

   This week the parliamentary science and technology select committee
   looked into the evidence behind the MHRA’s decision to allow homeopathy
   sugar pill labels to make medical claims without evidence of efficacy,
   and the funding of homeopathy on the NHS. There were some comedy
   highlights, as you might expect from any serious enquiry into an
   industry where sugar pills have healing powers conferred upon them by
   being shaken with one drop of the ingredient which has been diluted, so
   extremely, that it equates to one molecule of the substance in a sphere
   of water whose diameter is roughly the distance from the earth to the
   sun.

   Read the rest of this entry »

Part two of my Radio 4 show on the placebo effect, 9pm tonight (Monday)

   August 25th, 2008 by Ben Goldacre in bad science, onanism, placebo,
   podcast | 31 Comments »

   image So tonight at  9pm on BBC Radio 4 (Monday) you can hear the
   second episode of my two-part miniseries on the placebo effect, one of
   the most effective and neglected evidence based treatments known to
   man.

   In this show we look at the ethical and practical implications of
   research into the placebo effect, and discuss whether it’s okay – or
   even necessary – to lie to patients. The answer, from me at any rate,
   is “no”. Read the rest of this entry »

Think yourself thin…

   August 23rd, 2008 by Ben Goldacre in bad science, placebo | 33 Comments
   »

   Ben Goldacre
   The Guardian,
   Saturday August 23 2008

   What I particularly enjoy is the spectacle of fat people – ideally
   drinking beer – watching television, while somewhere on the other side
   of the world citizens of all nations are getting some nice exercise in
   the Olympics (throwing javelins, jumping over metal bars, climbing lamp
   posts with banners, and running away from the water cannon). These are
   the people I imagine paying for gyms they never visit, while I am
   cheerfully cycling to work and carrying the shopping up the stairs.
   Read the rest of this entry »

My Placebo programme on BBC Radio 4

   August 18th, 2008 by Ben Goldacre in bad science, onanism, placebo | 30
   Comments »

   [060721_pills_vmedwidec.jpg] I’ve been so busy I completely failed to
   spot that this show went out earlier this evening. It’s a smashing
   programme I made with Matt Silver from the BBC Radio 4 Science Unit on
   the placebo effect.

   We charge through some of the most fun experiments in the field, and in
   part two we get all philosophical about what it means for mankind. Read
   the rest of this entry »

All bow before the might of the placebo effect, it is the coolest strangest
thing in medicine

   March 1st, 2008 by Ben Goldacre in homeopathy, placebo, regulating
   research | 31 Comments »

   Ben Goldacre
   The Guardian,
   Saturday March 1 2008

   It was fun to hear universal jubilation over the new meta-analysis
   showing once again that some antidepressants aren’t much cop in mild or
   moderate depression: most of all on the Today programme, where a
   newsreader said the industry was contesting the study on the basis that
   it was not in line “with patient experience”. I’ve always said that
   homeopaths mimic big pharma in their marketing spiel, but this is the
   first time I’ve seen it done the other way around, so bravo to pill
   peddlers of all shades. Read the rest of this entry »

Medicalisation – don’t take it lying down.

   September 29th, 2007 by Ben Goldacre in acupuncture, bad science,
   medicalisation, placebo | 69 Comments »

   Ben Goldacre
   The Guardian
   Saturday September 29 2007

   One thing that always fascinates me, as I tug on my pipe in this
   armchair, is how reductionist, how mechanical, how sciencey and medical
   we like our stories about the body to be. This week a major new study
   was published on acupuncture. Many newspapers said it showed
   acupuncture performing better than medical treatment: in fact it was 8
   million times more interesting than that.
   Read the rest of this entry »

Acupuncture and back pain: some interesting background references

   September 25th, 2007 by Ben Goldacre in acupuncture, bad science,
   placebo | 96 Comments »

   I was just on Radio 4′s PM program talking about the acupuncture study
   that’s in the news today, you can listen to it here (37 minutes in to
   the programme):

   www.bbc.co.uk/radio4/news/pm/

   Here are some references and background bits and bobs.

   The paper itself was very interesting. It took 1200 people, with an
   average of 8 years back pain each: we can assume not been helped by
   biomedical treatments. They were split into three groups: one group had
   medical treatment; one group had proper, real, bells and whistles,
   needles in the “meridiens” acupuncture; and one group were treated with
   pretend acupuncture. Read the rest of this entry »

Homeopathy gives you Aids

   September 15th, 2007 by Ben Goldacre in homeopathy, MMR, placebo | 48
   Comments »

   Ben Goldacre
   The Guardian
   September 15th, 2007

   Okay now look: there’s nothing wrong with the idea of homeopaths giving
   out sugar pills. The placebo effect can be very powerful, because it’s
   not just about the pill, it’s about the cultural meaning of the
   treatment: so we know from research that four placebo sugar pills a day
   are more effective than two for eradicating gastric ulcers (and that’s
   not subjective, you measure ulcers by putting a camera into your
   stomach); we know that salt water injections are a more effective
   treatment for pain than sugar pills, not because salt water injections
   are medically active, but because injections are a more dramatic
   intervention; we know that green sugar pills are a more effective
   anxiety treatment than red ones, not because of any biomechanical
   effect of the dyes, but because of the cultural meanings of the colours
   green and red. We even know that packaging can be beneficial. Read the
   rest of this entry »
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The golden arse beam method.

   July 9th, 2011 by Ben Goldacre in alternative medicine, irrationality
   research, placebo | 15 Comments »

   Ben Goldacre, The Guardian, Saturday 9 July 2011

   Since I was a teenager, whenever I have a pivotal life event coming –
   an exam, or an interview – I perform a ritual. I sit cross-legged on
   the floor, and I imagine an enormous golden beam of energy coming out
   of my arse. Read the rest of this entry »

Placebo! Nocebo!

   April 17th, 2010 by Ben Goldacre in onanism, placebo, podcast | 29
   Comments »

   Hi, two quick videos… one on the mighty placebo effect, via NHS
   Choices, one on the nocebo effect from Nerdstock. Read the rest of this
   entry »

All bow before the mighty power of the nocebo effect

   November 28th, 2009 by Ben Goldacre in homeopathy, placebo | 70
   Comments »

   Ben Goldacre, Saturday 28 November 2009, The Guardian

   This week the parliamentary science and technology select committee
   looked into the evidence behind the MHRA’s decision to allow homeopathy
   sugar pill labels to make medical claims without evidence of efficacy,
   and the funding of homeopathy on the NHS. There were some comedy
   highlights, as you might expect from any serious enquiry into an
   industry where sugar pills have healing powers conferred upon them by
   being shaken with one drop of the ingredient which has been diluted, so
   extremely, that it equates to one molecule of the substance in a sphere
   of water whose diameter is roughly the distance from the earth to the
   sun.

   Read the rest of this entry »

Part two of my Radio 4 show on the placebo effect, 9pm tonight (Monday)

   August 25th, 2008 by Ben Goldacre in bad science, onanism, placebo,
   podcast | 31 Comments »

   image So tonight at  9pm on BBC Radio 4 (Monday) you can hear the
   second episode of my two-part miniseries on the placebo effect, one of
   the most effective and neglected evidence based treatments known to
   man.

   In this show we look at the ethical and practical implications of
   research into the placebo effect, and discuss whether it’s okay – or
   even necessary – to lie to patients. The answer, from me at any rate,
   is “no”. Read the rest of this entry »

Think yourself thin…

   August 23rd, 2008 by Ben Goldacre in bad science, placebo | 33 Comments
   »

   Ben Goldacre
   The Guardian,
   Saturday August 23 2008

   What I particularly enjoy is the spectacle of fat people – ideally
   drinking beer – watching television, while somewhere on the other side
   of the world citizens of all nations are getting some nice exercise in
   the Olympics (throwing javelins, jumping over metal bars, climbing lamp
   posts with banners, and running away from the water cannon). These are
   the people I imagine paying for gyms they never visit, while I am
   cheerfully cycling to work and carrying the shopping up the stairs.
   Read the rest of this entry »

My Placebo programme on BBC Radio 4

   August 18th, 2008 by Ben Goldacre in bad science, onanism, placebo | 30
   Comments »

   [060721_pills_vmedwidec.jpg] I’ve been so busy I completely failed to
   spot that this show went out earlier this evening. It’s a smashing
   programme I made with Matt Silver from the BBC Radio 4 Science Unit on
   the placebo effect.

   We charge through some of the most fun experiments in the field, and in
   part two we get all philosophical about what it means for mankind. Read
   the rest of this entry »

All bow before the might of the placebo effect, it is the coolest strangest
thing in medicine

   March 1st, 2008 by Ben Goldacre in homeopathy, placebo, regulating
   research | 31 Comments »

   Ben Goldacre
   The Guardian,
   Saturday March 1 2008

   It was fun to hear universal jubilation over the new meta-analysis
   showing once again that some antidepressants aren’t much cop in mild or
   moderate depression: most of all on the Today programme, where a
   newsreader said the industry was contesting the study on the basis that
   it was not in line “with patient experience”. I’ve always said that
   homeopaths mimic big pharma in their marketing spiel, but this is the
   first time I’ve seen it done the other way around, so bravo to pill
   peddlers of all shades. Read the rest of this entry »

Medicalisation – don’t take it lying down.

   September 29th, 2007 by Ben Goldacre in acupuncture, bad science,
   medicalisation, placebo | 69 Comments »

   Ben Goldacre
   The Guardian
   Saturday September 29 2007

   One thing that always fascinates me, as I tug on my pipe in this
   armchair, is how reductionist, how mechanical, how sciencey and medical
   we like our stories about the body to be. This week a major new study
   was published on acupuncture. Many newspapers said it showed
   acupuncture performing better than medical treatment: in fact it was 8
   million times more interesting than that.
   Read the rest of this entry »

Acupuncture and back pain: some interesting background references

   September 25th, 2007 by Ben Goldacre in acupuncture, bad science,
   placebo | 96 Comments »

   I was just on Radio 4′s PM program talking about the acupuncture study
   that’s in the news today, you can listen to it here (37 minutes in to
   the programme):

   www.bbc.co.uk/radio4/news/pm/

   Here are some references and background bits and bobs.

   The paper itself was very interesting. It took 1200 people, with an
   average of 8 years back pain each: we can assume not been helped by
   biomedical treatments. They were split into three groups: one group had
   medical treatment; one group had proper, real, bells and whistles,
   needles in the “meridiens” acupuncture; and one group were treated with
   pretend acupuncture. Read the rest of this entry »

Homeopathy gives you Aids

   September 15th, 2007 by Ben Goldacre in homeopathy, MMR, placebo | 48
   Comments »

   Ben Goldacre
   The Guardian
   September 15th, 2007

   Okay now look: there’s nothing wrong with the idea of homeopaths giving
   out sugar pills. The placebo effect can be very powerful, because it’s
   not just about the pill, it’s about the cultural meaning of the
   treatment: so we know from research that four placebo sugar pills a day
   are more effective than two for eradicating gastric ulcers (and that’s
   not subjective, you measure ulcers by putting a camera into your
   stomach); we know that salt water injections are a more effective
   treatment for pain than sugar pills, not because salt water injections
   are medically active, but because injections are a more dramatic
   intervention; we know that green sugar pills are a more effective
   anxiety treatment than red ones, not because of any biomechanical
   effect of the dyes, but because of the cultural meanings of the colours
   green and red. We even know that packaging can be beneficial. Read the
   rest of this entry »
   « Older Entries

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   Biology 202
   1999 First Web Reports
   On Serendip

   This paper reflects the research and thoughts of a student at the time
   the paper was written for a course at Bryn Mawr College. Like other
   materials on Serendip, it is not intended to be "authoritative" but
   rather to help others further develop their own explorations. Web links
   were active as of the time the paper was posted but are not updated.

   Contribute Thoughts | Search Serendip for Other Papers | Serendip Home
                                    Page

                         Therapeutic Placebo Effect:
                           A Mind/Body Connection

                            Patricia Anne Kinser
     __________________________________________________________________

                        reformatted from original at
           http://students.haverford.edu/pkinser/neuro-placebo.htm
     __________________________________________________________________

     Imagine you go to your doctor for chronic back pain and she tells
     you that she's going to give you a drug, yet she's not sure of its
     effectiveness because only approximately 40% of her patients have
     found it to be beneficial. How sure will you be that the outcome of
     this treatment will be positive? However, what if your doctor tells
     you she is giving you the newest, most beneficial drug treatment on
     the market and that she is very sure of how helpful it will be?
     Imagine the difference just a simple positive statement from your
     doctor will make when you take the pill every day. Not only will you
     be trusting of your treatment, but that trust will lead you to be
     confident ^(Endnote 1) that you will feel better - and in most
     cases, you will.

     This is an example of the placebo effect - a self-made natural
     healing response of the body. No matter the fact that in both
     instances your doctor is giving you the same medication, her belief
     and yours in the treatment will most likely result in more positive
     effects. Many people argue that alternative methods of healing (such
     as hypnosis, therapeutic touch, homeopathic remedies, etc) are
     basically a placebo effect taking place. Yet, doesn't this fact
     prove the power of our minds both in health and in issues of pain
     management? Most modern scientists tend to separate the mind from
     the body, at least implicitly, suggesting the "mind" is simply a
     construct with little meaning. The one-cause, one- cure philosophy
     of science today often disregards the role of the mind in health and
     healing. Yet many of us even daily acknowledge the power of the mind
     when we say "oh, you're not sick- it's all in your mind". The
     placebo effect is not totally understood, yet this fact should not
     lead anyone to believe that its effects should be discounted. The
     placebo effect has been documented to be very powerful.

     A placebo is a medicine or other kind of treatment that seems
     therapeutic, but in reality is inert and pharmacological inactive
     ^(2). The placebo effect is "a change in a patient's illness
     attributable to the symbolic import of a treatment rather than a
     specific pharmacologic or physiologic property" ^(3). Note that a
     placebo is not even necessary to result in a placebo effect.
     Basically, the only way this treatment can work is if one believes
     that it will. No matter the fact that placebos lack actual chemical
     functioning, it has been documented that 30-40% of patients
     experience the positive effects of placebo ^(2, 5, 7). We most often
     hear of placebos in clinical tests of new medications or treatments,
     where one group in the study is given the actual medication and the
     other receives a placebo which feels, tastes, appears exactly like
     the drug. The placebo group's reactions to the placebo serve as a
     base-line against which the effects of the drug can be studied. In
     order for this drug to be considered effective, the treatment being
     tested much produce results better than those by the placebo. Most
     often, the patient's belief that the placebo will be positively
     effective is a self-fulfilling prophecy.

     A patient's belief in the treatment and the placebo response are
     dependent upon a variety of factors. First, the patient's
     expectations of treatment effects clearly influence the responses.
     For example, a study in England was done where 100 men were told
     that they were taking chemotherapy, when in actuality they were
     taking inactive saline solution. 20% of these men lost their hair,
     demonstrating the power of the belief of effects of the treatment.
     ^(4) Second, the relationship between patient and care-provider is
     quite important in determining treatment (or placebo) results. If
     there is a positive rapport between the two, then most often there
     will be a positive enthusiasm for the treatment, and therefore a
     positive outcome, no matter if a placebo or pharmacologic treatment
     was used. The friendliness, interest, sympathy, prestige, and
     positive attitude of the care- provider toward the patient and
     toward the treatment are associated with positive effects of
     placebos as well as of active treatments. For example, in a double-
     blind study of dental extractions, two groups were compared: the
     first, where the doctors knew they would administer either a
     narcotic analgesic, a placebo, or a narcotic antagonistic and the
     second, where the doctors knew they would administer either a
     placebo or narcotic antagonist. The patients from the first group
     who received placebo had significantly less pain. Since the two
     placebo groups were only different in the doctors' knowledge of
     possible treatment, this knowledge must have resulted in differences
     in behaviors by the doctor that influenced patient responses ^(3).
     Third, placebos have time- effect curves and peaks, cumulative and
     carryover effects after end of treatment which are quite similar to
     those of pharmacologically active medications. For example, "when
     varying doses of analgesic followed by a placebo are administered,
     patients' placebo responses correspond in degree of pain relief over
     time to their original dosage of analgesic" ^(3). In addition,
     dose-response effects have also been documented where two placebo
     pills were demonstrated to have more pronounced effects than one.

     How does one explain these trends and effectiveness of a placebo
     treatment? The physiology of the placebo effect is still largely
     unknown. A placebo is chemically inactive, yet it has a profound
     effect on the human mind and body. A possible explanation is that a
     patient's belief in the treatment will reduce anxiety by allowing
     the problem to seem more controllable. With regards to the example
     given at the beginning of the paper, you may feel much more at ease
     once a doctor has told you that there are effective treatments for
     your pain, therefore you can reap the benefits of a less-stressed
     state. Depression and anxiety most often increase subjective
     complaints of pain ^(5). Stress adversely affects several
     physiological processes and increases symptom reporting. Placebos
     seem "most effective for anxious patients and the effects are often
     attributed to anxiety reduction and associated decreased pain and
     suffering" ^(3). Thus, the patient may benefit from the relief of
     symptoms of depression, stress, and anxiety. In addition, the
     placebo does not merely allow the patient's mind to be at ease; the
     effect extends beyond the psyche. In a 1950 study of routine
     arterial ligation surgery to treat angina pectoris, 13 patients
     received the surgery while a placebo group of five had a chest
     incision made. 76% of those who received the surgery and 100% of the
     placebo group improved ^(7).

     Another explanation is the idea of conditioned stimuli. Treatment
     may have a positive effect because of its association with effective
     treatments (and interactions with the medical field) the patient has
     had before. Thus, inactive drugs, people, procedures, and places can
     function as conditioned stimuli for the alleviation of symptoms if
     powerful unconditioned stimuli has been positively associated
     repeatedly with the relief of symptoms.

     An additional possible explanation for the effects of placebo is
     that responses may be caused by endogenous opiate release in the
     central nervous system ^(3). Pain sensation is subject to circuitry
     within the nervous system that uses opioid synapses, as suggested by
     the fact that injection of opiates relieves pain. It is thought that
     possibly the placebo effect is a stimulation and release of our
     body's own natural narcotics, such as endorphins and enkephalins.
     These chemicals are typically released during stress or excitement
     and it is possible that they either bind to pain receptors or
     depress neurons in the central nervous system, thus slowing or
     eliminating pain communication ^(6). This shows us that, by whatever
     mechanism, a person's beliefs can either change his biochemistry or
     functionally mimic a change in biochemistry. However, studies of the
     exact physiological mechanism of the placebo effect are rare and
     difficult, especially when in most cases the use of a placebo is to
     test the effect of another drug. Additionally, since we know that
     the effect of placebos is dependent upon conditioning, faith and
     reduction of anxiety, the placebo response is different for everyone
     and cannot be necessarily predicted.

     Indeed, we may not know how the placebo works, yet something which
     makes such profound therapeutic changes must not be ignored. Many
     scientists believe that the effectiveness of alternative therapies
     may simply be a placebo effect. Yet, if the effects of treatments
     such as hypnosis, meditation, acupuncture, etc... remain and bring
     about long- lasting health benefits, then we must draw the
     conclusion that a placebo is more than something against which
     testing of a "real" drug should be done. Given the positive results
     of the placebo effect, how can we really say that one type of
     medicine or therapy is necessarily ineffective? For example,
     relaxation techniques generally alter sympathetic activity as
     indicated by decreases in oxygen consumption, respiratory and heart
     rate, and blood pressure. Increased electroencephalographic slow
     wave activity has also been reported. Although the mechanism for the
     decrease in sympathetic activity is unclear, one may infer that
     decreased arousal (due to alterations in catecholamines or other
     neurochemical systems) plays a key role. Hypnosis, in part because
     of its capacity for evoking intense relaxation, has been reported to
     reduce several types of pain. Finally, acupuncture has gained
     popularity in its ability to relieve pain, possibly due to the
     release of endorphins ^(5). In addition, these types of techniques
     may alter expectation, which also plays a key role in subjective
     experiences of pain intensity. They also may augment analgesic
     responses through behavioral conditioning. Finally, these techniques
     help patients enhance their sense of self control over their illness
     enabling them to be less helpless and better able to deal with pain
     sensations ^(5). If these are positive effects of alternative
     therapies (which the medical world claims are placebo effects), then
     the placebo effect must demonstrate the amazing power of our mind.

     Perhaps the placebo decreases anxiety. Perhaps it meets the
     expectations of the patient. Perhaps it is a conditioned response.
     Yet, the issue here is that it works. Why does much of the Western
     world of medicine reject a "technology" that works - the power of
     our minds? Most doctors shy away from the use of the word because it
     seems to imply a type of deception. And yet, the deception is all in
     our heads! "Placebo effects are recognized as an inherent part of
     any therapeutic intervention outcome, and demonstrate the important
     and power of the psychological factors in the healing process" ^(1).
     The placebo effect is proof of the fact that the mind can influence
     the body in a powerful and therapeutic way.
     Citations

     1- Fecteau, Danielle, "Placebo Effects", Science et Comportement
     http://www.ovid.med.virginia.edu/ovidweb/ovidweb.cgi

     2- American Cancer Society, Alternative and Complementary Therapies:
     http://www.cancer.org/alt_therapies/articles/placebo.html

     3- Turner, et al, "The importance of placebo effects in pain
     treatment and research", JAMA, 1994: http://www.ovid.med.
     virginia.edu/ovidweb/ovidweb.cgi

     4- Mining Co. Alternative Medicine Information:
     http://www.altmedicine.minigco.com/library/weekly/aa100998.htm?terms
     =placebo+eff ect&COB=home (Note: this link takes you to the Mining
     Co. search engine)

     5- Mind/Body Medicine Discussion:
     http://www2.trincoll.edu/~rmlee/mindbody_lll/mb2disc_frm.htm

     6- Elmer, Debra, "Placebo Use":
     http://www.nursing.uiowa.edu/sites/Adultpain/MedGen/placebot.htm

     7- Imprint Online, "Placebo Power":
     http://imprint.uwaterloo.ca/issues/012398/3Science/science01.shtml
     Endnotes

     1- "confident" literally means "with faith" (Lat: con = with; fides
     = faith)

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     * The Placebo Effect: Transforming Biology With Belief

The Placebo Effect: Transforming Biology With Belief

   July 21, 2013 by Arjun Walia. 35 Comments.
   (BUTTON)   Share on Facebook (BUTTON)   Twitter

   placebo Did you know that we can change our biology simply by what we
   believe to be true? The placebo effect is defined as the measurable,
   observable, or felt improvement in health or behaviour not attributable
   to a medication or invasive treatment that has been administered. It
   suggests that one can treat various ailments by using the mind to heal.
   For example, if two people have a head ache and one takes tylenol while
   the other is given a pill that contains nothing (sugar), both could
   report that the pill was successful and the headache is gone. The
   difference is, the one that was given the pill which contained nothing
   still believed that they were given a tylenol that would alleviate
   their headache. In doing so,  their headache was cured because of what
   they believed to be true. This has happened on numerous occasions, many
   studies have shown that the placebo effect is real and highly
   effective.

   The placebo practice is known, but widely dismissed in medicine. The
   placebo effect should be a major topic of study in medical schools.
   Unfortunately drug companies study patients who respond to the placebo
   effect with the goal of eliminating them from early clinical trials. It
   bothers pharmaceutical manufacturers that in most of their clinical
   trials the placebos prove to be just as effective as their chemical
   ridden drugs. Examining the placebo effect would give rise to a whole
   new category under science, which would probably be consciousness. This
   is why it’s not examined thoroughly, the power of our perception and
   its ability to create our reality and even change our biology would
   open the door to a multitude of other questions, possibilities and
   potentialities for the human race. These potentialities would most
   likely wipe out many industries on the planet, from health all the way
   down to energy. These concepts are also heavily examined and
   illustrated by quantum physics.

     The placebo effect should be the subject of major, funded research
     efforts. If medical researchers could figure out how to leverage the
     placebo effect, they would hand doctors an efficient,energy-based,
     side effect-free tool to treat disease. Energy healers say they
     already have such tools, but I am a scientist, and I believe the
     more we know about sceince of the placebo, the better we’ll be able
     to use it in clinical settings – Bruce Lipton, Ph.D (3)

   A Baylor School of Medicine study, published in 2002 in the New England
   Journal of Medicine, (1) looked at surgery for patients with severe and
   debilitating knee pain. Many surgeons know there is no placebo effect
   in surgery, or so most of them believe. The patients were divided into
   three groups. The surgeons shaved the damaged cartilage in the knee of
   one group. For the second group they flushed out the knee joint,
   removing all of the material believed to be causing inflammation. Both
   of these processes are the standard surgeries people go through who
   have severe arthritic knees. The third group received a “fake” surgery,
   the patients were only sedated and tricked that they actually had the
   knee surgery. For the patients not really receiving the surgery, the
   doctors made the incisions and splashed salt water on the knee as they
   would in normal surgery. They then sewed up the incisions like the real
   thing and the process was complete. All three groups went through the
   same rehab process, and the results were astonishing. The placebo group
   improved just as much as the other two groups who had surgery.

     My skill as a surgeon had no benefit on these patients. The entire
     benefit of surgery for osteoarthritis of the kneww was the placebo
     effect – Dr. Moseley (Surgeon involved in the study)(3)

   Another great example of the placebo effect came from the United States
   Department of Health and Human Services in 1999. The report discovered
   that half of severely depressed patients taking drugs improve compared
   to the thirty-two percent taking a placebo. Don’t forget about all of
   the side effects and dangers that have been associated with
   antidepressants every year. Don’t forget that the ‘depression industry’
   alone is a multi billion dollar one(3).

   A 2002 article published in the American Psychological
   Association’s prevention & treatment, by University of Connecticut
   psychology professor Irving Kirsch titled, “The Emperor’s New Drugs,”
   made some more shocking discoveries(5)(4). He found that 80 perecent of
   the effect of antidepressants, as measured in clinical trials, could be
   attributed to the placebo effect. This professor even had to file a
   Freedom of Information Act (FOIA) request to get information on the
   clinical trials of the top antidepressants.

     The difference between the response of the drugs and the response of
     the placebo was less than two points on average on this clinical
     scale that goes from fifty to sixty points. That’s a very small
     difference, that difference is clinically meaningless – Professor
     Kirsch

   Researchers all over the world have found that placebo treatments can
   stimulate real biological and physiological responses. Everything from
   changes in heart rate to blood pressure and even chemical activity in
   the brain. It’s been effective with a number of different ailments from
   arthritis, depression, fatigue, anxiety, Parkinson’s and more (2)

   So what does this mean?

   It means that through the power of belief, your biological body can
   react in a necessary way to target whatever ailment you are
   experiencing. Thoughts, feelings, and emotions are directly responsible
   for changing  your biology. If we look at depression for example, we
   are told the main cause of it is a chemical deficit in the brain. But
   if thoughts, feelings and emotions can release different chemicals in
   the brain, why not just work on the patients feelings to induce a
   different chemical state? If our feelings, emotions and thoughts are
   directly correlated with our biology, why aren’t we putting more
   resources into this research? Why is this not practiced by the medical
   industry? Why do we completely turn a blind eye to it?

   The human race has been trained, and programmed to believe that
   external medicines are necessary for all ailments. I’m not saying that
   some medical applications are not valid, I’m just saying the human race
   completely ignores the power of non-physical phenomenon. We continue to
   believe that we need something outside of ourselves to heal, when
   everything points to the fact that this is not entirely true. Our own
   biological system and the human being is very capable of healing
   itself. We just don’t know how, we don’t believe it, we are not exposed
   to it.

   Changing your biology with belief is not an easy process, because most
   of us don’t truly believe we can. We are going up against years of
   perceptual manipulation that have formed our thoughts and beliefs. Your
   beliefs shape your perception, and your perception is what creates real
   phenomenon. If you change the way you perceive things, the things you
   perceive change. We are powerful beings,  and have abilities that have
   yet to be unlocked.  I believe that these types of realities will
   continue to  emerge  and will be implemented in the future. The placebo
   effect demonstrates, from a biological standpoint, that what you
   believe indeed becomes your reality. For one to be able to use this,
   they must believe it. One must perceive it as real as the perceive
   their own hand real, the sun real, the stars real. It’s not about
   believing, it’s about knowing.

   The true nature of reality has yet to be discovered, but we continue to
   progress in our understanding. As we progress we realize how obsolete
   our current way of functioning really is. It’s time to evolve past our
   archaic ideas and false beliefs, and step into a new understanding of
   reality. We are capable of so much more, or potential is limitless.

   Sources:

   (1)http://www.nejm.org/doi/full/10.1056/NEJMoa013259

   (2)http://harvardmagazine.com/2013/01/the-placebo-phenomenon

   (3)Lipton, Bruce. The Biology of Belief. Hay House, Inc, 2005

   (4)http://www.scientificamerican.com/article.cfm?id=mind-reviews-the-em
   perors-new-drugs

   (5)http://psycnet.apa.org/?&fa=main.doiLanding&doi=10.1037/1522-3736.5.
   1.523a

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About the author

Arjun Walia

   arjun@collective-evolution.com
   My Articles

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35 comments on “The Placebo Effect: Transforming Biology With Belief”

    1. darkmoon
       December 2, 2013 at 4:42 am
       what about migraine ? is it just all psychologically driven and can
       a placebo also help alleviate migraine pain?
       Reply
    2. RAHEEM REMTULLA
       November 7, 2013 at 10:10 pm
       Im done with this…………………………
       Reply
    3. Pingback: Efeito Placebo: Transformando a sua biologia através da
       convicção. « METANOIAN
    4. Pingback: Thou mind’s power to heal – The Placebo Effect | Rajkamal
       Mohanram's Blog
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    8. Dave Kool
       August 14, 2013 at 12:25 am
       There was a similar study done where some basketball players were
       divided into three groups: one that would practice free throws for
       an hour a day, one who would only visualize practicing free throws
       for an hour a day, and the final group did basically nothing.
       Predictably the group that did nothing showed no improvement on the
       number of baskets they made, the group that practiced showed the
       most improvement, but interestingly enough, the group who only
       VISUALIZED practicing their free throws showed a marked
       improvement, almost as much as the group who was actually
       practicing. Just goes to show that perception and visualization are
       nearly as important as actions themselves.
       Reply
          + Rich
            August 15, 2013 at 11:09 am
            In all kindness in addition:
            A ‘study’ is also the creating of a reality version.
            (“We are not the cool observers of the world, but its
            “passionate creators” — we are all poets and the world is our
            metaphor.” – Roger S. Jones)
            After all it is a possibility in the dream state of
            consciousness to to create and experience a similar experience
            of being real.
            Science aka ‘knowledge’, ‘science fiction’ is a product of
            imagining.
            Reply
          + Rich
            August 15, 2013 at 2:40 pm
            In addition and in all kindness.
            “I see no ships
            European explorers found indigenous peoples unable to see
            their tallships – or did they?
            By David Hambling
            February 2007
            Are people blind to unexplained phenomena because their brains
            simply can’t handle anything they don’t understand? This
            story, quoted in social science circles and popular with New
            Agers, was repeated in the recent film What The Bleep Do We
            Know? – “When the tall European ships first approached the
            early Native Americans, it was such an ‘impossible’ vision in
            their reality that their highly filtered perceptions couldn’t
            register what was happening, and they literally failed to
            ‘see’ the ships.”
            A more detailed account, “allegedly found in a diary in
            Magellan’s own handwriting”, 2 describes how South Americans
            could see the boats that the explorers landed in, but not the
            ships anchored offshore. [...]”
            http://tinyurl.com/ybjbzbe
            &
            “Gautama Buddha [...]
            We are what we think.
            All that we are arises with our thoughts.
            With our thoughts we make the world. [...]”
            http://tinyurl.com/lae32pt
            &
            “Numerical Cognition Without Words: Evidence from Amazonia
            1. Peter Gordon
            Members of the Pirahã tribe use a “one-two-many” system of
            counting. I ask whether speakers of this innumerate language
            can appreciate larger numerosities without the benefit of
            words to encode them. This addresses the classic Whorfian
            question about whether language can determine thought [...]”.
            http://tinyurl.com/mwuujnc
            The information which, for one , is used to (co-) create with,
            is aka ‘language’. According to ‘Ethnologue’ there are about
            7,105 languages.
            http://tinyurl.com/m6cbev8
            These 7,105 languages consist out of a multitude of concepts
            (information). Being ignorant of most all of these concepts
            also means that (co-) creating realities using all these
            concepts is impossible.
            No information for ‘tall ships’ also means no focusing with
            this information, and no (co-) creating of a reality with
            ‘tall ships’. This also applies to the ‘holographic illusion’
            know as ‘New York’ , or ‘histories’ or what ever.
            (Reality is merely an illusion, albeit a very persistent one.
            – Albert Einstein -(Adjusted version: Reality is merely an
            illusion, albeit a very persistent holographic one. ))
            “We are what we think.”
            But we can only use the tools we have. When those ’tools’ aka
            ‘languages/concepts’ are lacking, they cannot be used to (co-)
            create realities with. When those ’tools’ aka
            ‘languages/concepts’ are alternatives, (co-) created
            alternative realties manifest.
            Numerical Cognition is using ‘languages/concepts’ to (co-)
            create with. When these ‘language/concepts’ are lacking (being
            ignorant of these concepts), (co-) creating with these
            ‘languages/concepts’ is impossible.
            Ignorance is bliss and is most common!
            Being ignorant of the information regarding an activity and to
            take or have a part in or share this activity, is impossible.
            Even if according to ‘language/concepts’ it is an ‘illness’, a
            ‘sport’ or ‘whatever’.
            In all cases ‘energy’ cannot assume holographic form
            manifestations, if the information (for one
            ‘languages/concepts) in use to focus with, is lacking.
            Regarding holograms:
            “Japanese scientists create touchable holograms.”
            For one: http://tinyurl.com/2996nyw
            Is Our Universe a Hologram? In 1982 a Litttle Known but Epic
            Event Occured at the University of Paris (Today’s Most
            Popular)
            For one: http://tinyurl.com/6e5nlu4
            *Definition:
            “Everything is a holographic energy form variation
            manifestation, within consciousness, by which energy assumes
            the holographic form variation and manifests as a holographic
            reflection relative to the information* which is in use to
            focus with and in doing so co-create with.”
            Reply
               o Rich
                 August 15, 2013 at 7:59 pm
                 Motto:
                 Errors fail to become by means of propagation in
                 multitude.
                 Verify everything – The Buddha.
                 Thus the following corrections;
                 Questioning perceptual blindness
                 I see no ships
                 http://tinyurl.com/ybjbzbe
                 Gautama Buddha
                 http://tinyurl.com/lae32pt
                 Numerical Cognition Without Words: Evidence from Amazonia
                 http://tinyurl.com/3pg4ncv
                 Is Our Universe a Hologram? In 1982 a Litttle Known but
                 Epic Event Occured at the University of Paris (Today’s
                 Most Popular)
                 http://tinyurl.com/6e5nlu4
                 The information which, for one , is used to (co-) create
                 with, is aka ‘language’. According to ‘Ethnologue’ there
                 are about 7,105 languages.
                 http://tinyurl.com/m6cbev8
                 Japanese scientists create touchable holograms.
                 http://tinyurl.com/2996nyw
                 Is Our Universe a Hologram? In 1982 a Litttle Known but
                 Epic Event Occured at the University of Paris (Today’s
                 Most Popular)
                 http://tinyurl.com/6e5nlu4
                 Reply
    9. Pingback: Re-Write Reality. | ThirdiRadio
   10. Pingback: The Placebo Effect: Transforming Biology With Belief |
       Phoenix Tree Productions
   11. Will van Tienen
       August 3, 2013 at 4:25 pm
       There is no difference between energy and material! It’s all the
       same principle: Religion, Mantra, Belief, Mindfullness, The Secret.
       You create your own reality. You just have to believe it yourself!
       Reply
          + Rich
            August 5, 2013 at 4:31 am
            Kindly in addition:
            Energy is conscious, holographic, formless, transformable.
            Focusing information and energy assumes holographic forms
            which manifest.
            Language and cultural codes:
            “How does relativity theory resolve the Twin Paradox?”
            Ronald C. Lasky, a lecturer at Dartmouth College’s Thayer
            School of Engineering, explains.
            Time must never be thought of as pre-existing in any sense; it
            is a manufactured quantity. –Hermann Bondi..” [...]
            http://tinyurl.com/llggv9m
            Altering the information which is in use to focus with, also
            alters the manifestation accordingly.
            In regard to the “Twin Paradox” substituting the persons, for
            one, known as ‘The Twins’ with persons, for one known as
            ‘Mother and her child’ and the manifestation is accordingly.
            The person ‘the mother’ , being the person who travels with
            the rocket, and the person ‘the child’ who remains on earth,
            at a certain point according to the information know as the
            “Twin Paradox/Mother and Child Paradox” are ‘equally old’ and
            at another point ‘the mother is younger than her own child’
            and ‘the child is older than it’s own mother’.
            Consciousness:
            “A honours degree in mathematics with “no detectable brain”?
            Consciousness
            The predominant view amongst neuroscientists is that human
            consciousness is a product of the electrical activity of the
            brain. They call it an “emergent property” of grey matter. The
            basic assumption there is that if you take approximately 100
            billion nerve cells and you wire them together through a
            prodigious network of connection, consciousness somehow
            “emerges” spontaneously from that complexity. One neuron is
            not conscious, but 100 billion, taken together, are.
             This materialist theory of consciousness is up against some
            formidable challenges, all happily ignored by the mainstream
            materialist neuroscientists. [...]
            A brain is also a holographic manifestation with in
            consciousness, a possibility but not a necessity.
            “Grey Walter’s Anticipatory Tortoises” lack a brain
            manifestation altogether, yet have consciousness.
            http://tinyurl.com/q8q42lh
            Focusing information:
            Jacko deemed to be a gorilla of Amsterdam Zoo Artis, in
            percentages, is doing ‘remarkably’ well buying and selling
            shares for years.
            Those persons who are deemed to be Jacko’s caretakers however
            are the beings who are focusing the information and believe
            Jacko’s share picks/instructions.
            http://tinyurl.com/l4aq47o
            Altering information and thus altering possible beliefs:
            There is no such thing as a “Nobel Prize In Economics”.
            There is “The Sveriges Riksbank Prize in Economic Sciences in
            Memory of Alfred Nobel”. A prize of the central bank of
            Sweden.
            http://tinyurl.com/ldf2724
            http://tinyurl.com/l4z46e5
            It is however possible to use language and pretend there is a
            “Nobel Prize In Economics”.
            http://tinyurl.com/88f76fv
            Energy doesn’t judge, it just assumes holographic forms which
            manifest and can be propagated as beliefs.
            http://tinyurl.com/88f76fv
            Reply
               o Rich
                 August 6, 2013 at 10:01 pm
                 Link for
                 “…Consciousness:
                 “A honours degree in mathematics with “no detectable
                 brain”?…”
                 Link: http://tinyurl.com/kgqyhpv
                 Reply
                    # Rich
                      August 9, 2013 at 7:36 am
                      The principle of the definition* also applies for
                      the conceptualization known as:
                      “…self-fulfilling prophecy
                      Any positive or negative expectation about
                      circumstances, events, or people that may affect a
                      person’s behavior toward them in a manner that
                      causes those expectations to be fulfilled.
                      An employer who, for example, expects the employees
                      to be disloyal and shirkers, will likely treat them
                      in a way that will elicit the very response he or
                      she expects. …”
                      http://tinyurl.com/kb4s3as
                      “…Self-fulfilling prophecy
                      From Wikipedia, the free encyclopedia
                      A self-fulfilling prophecy is a prediction that
                      directly or indirectly causes itself to become true,
                      by the very terms of the prophecy itself, due to
                      positive feedback between belief and behavior.
                      Although examples of such prophecies can be found in
                      literature as far back as ancient Greece and ancient
                      India, it is 20th-century sociologist Robert K.
                      Merton who is credited with coining the expression
                      “self-fulfilling prophecy” and formalizing its
                      structure and consequences. In his book Social
                      Theory and Social Structure, Merton defines
                      self-fulfilling prophecy in the following terms:
                      e.g. when Roxanna falsely believes her marriage will
                      fail, her fears of such failure actually cause the
                      marriage to fail. …”
                      http://tinyurl.com/kyxvmty
                      *Definition:
                      “Everything is a holographic energy form variation
                      manifestation, within consciousness, by which energy
                      assumes the holographic form variation and manifests
                      as a holographic reflection relative to the
                      information* which is in use to focus with and in
                      doing so co-create with.”
                      Reply
                         @ Rich
                           August 9, 2013 at 3:58 pm
                           “Obese? Smoker? No Retirement Savings? Perhaps
                           It’s Because of the Language You Speak
                           Why can’t the Greeks be more like the Germans?
                           Could it be because they speak Greek? There’s
                           no doubt some nations save more money than
                           others, and plan better for retirement, and
                           watch their collective weight, but the proposed
                           explanations for different levels of
                           future-mindedness have been historical,
                           sociological, cultural and psychological—not
                           grammatical. In this ingenious paper (pdf),
                           though, M. Keith Chen argues that syntax plays
                           a role. His analysis suggests that if your
                           language’s syntax blurs the difference between
                           today and tomorrow (as do, say, Chinese and
                           German) then you are more likely to save money,
                           ….”
                           http://tinyurl.com/9aqaose
                           &
                           “In New Quantum Experiment, Effect Happens
                           Before Cause
                           A real-world demonstration of a thought
                           experiment conducted at the University of
                           Vienna, has produced a result that is somewhat
                           befuddling to people with what the lead
                           researcher calls a “naïve classical world
                           view.” Two pairs of particles are either
                           quantum-entangled or not. One person makes the
                           decision as to whether to entangle them or not,
                           and another pair of people measure the
                           particles to see whether they’re entangled or
                           not.
                           The head-scratcher is: the measurement is made
                           before the decision is made, and it is
                           accurate. “Classical correlations can be
                           decided after they are measured,” says
                           Xiao-song Ma, the writer of the study.
                           Entanglement can be created “after the
                           entangled particles have been measured and may
                           no longer exist.” …”
                           http://tinyurl.com/7b7dj3u
                           Albert Einstein’s ‘Spukhafte Fernwirkung’ is
                           about instantaneous manifestation. There is
                           neither cause nor effect.
                           Real-Time Imaging of Quantum Entanglement
                           YouTube
                           http://tinyurl.com/n5mehrs
                           However altering the information (languages for
                           one) which is in use to focus and create with
                           will also have energy assume forms accordingly
                           which manifest as a reality.
                           Using the information ‘effect happens before
                           cause’ is also possibly applicable for concepts
                           know as “virgin birth”.
                           http://tinyurl.com/8926j33
               o Rich
                 August 11, 2013 at 2:35 pm
                 “Splitting (also called all-or-nothing thinking) is the
                 failure in a person’s thinking to bring together both
                 positive and negative qualities of the self and others
                 into a cohesive, realistic whole. It is a common defense
                 mechanism used by many people.[1] The individual tends to
                 think in extremes (i.e., an individual’s actions and
                 motivations are all good or all bad with no middle
                 ground.)….”
                 http://tinyurl.com/d6czkxz
                 Albert Schweitzer, M.D. on the Doctor Within Every
                 Patient
                 “Within every patient there resides a doctor, and we as
                 physicians are at our best when we we put our patients in
                 touch with the doctor inside themselves.”
                 http://tinyurl.com/65goswb
                 The language (information) in use by Mr Albert Schweitzer
                 is ‘black & white’ . This ‘school of thought’ is for one
                 relative to the languages (information) known as the
                 “Abrahamic religions” (Judaism, Christianity, Islam, and
                 Bahá’í Faith.)
                 http://tinyurl.com/6wjsvhf
                 And by shifting the focus from being a creator
                 (co-creator) to the being an observer, a “Wild Goose
                 Chase” manifests. Mr Albert Schweitzer not only (co-)
                 creates the ‘Doctor Within’, but also the ‘disease
                 within’, in his reality manifestation; but fails to
                 recognize that creating (co-creating) is at play, not
                 observing.
                 Energy just assumes forms-no matter what.
                 Reply
                    # Rich
                      August 14, 2013 at 1:01 am
                      Charles Robert Darwin’s ‘On the Origin of Species by
                      Means of Natural Selection, or the Preservation of
                      Favoured Races in the Struggle for Life.’ (The
                      Origin of Species.)
                      http://tinyurl.com/noxdjfa
                      “[...]WHEN we look to the individuals[...]”
                      The, for one, phenomenon Mr Charles R. Darwin’s
                      focus is a shifting from being a creator
                      (co-creator) to being an observer.
                      (“We are not the cool observers of the world, but
                      its “passionate creators” — we are all poets and the
                      world is our metaphor.” – Roger S. Jones)
                      The, for one, phenomenon Mr Charles R. Darwin fails
                      to account for and integrate into ‘The Origin of
                      Species’ the implications of, for instance: ‘the
                      blind spot’, ‘filtering of the senses’, ‘the
                      language concepts and conceptualizations (English
                      -black/white-deductive) in use’.
                      But does focus subconsciously, using the tools he
                      does have, incomplete as they are, information, and
                      energy just assumes holographic forms which
                      manifest.
                      Of course being ignorant of English and thus also of
                      ‘The Origin of Species’ beliefs, also has energy
                      remain formless, in this regard.
                      Reply
   12. Tahir C
       August 2, 2013 at 4:48 am
       Okay, so there’s no disagreement that humans are capable of doing
       much more. But there’s also a huge tendency of mixing up reality
       with illusion, and a very fine line separates out both from each
       other. I don’t want to get all hasty on getting quotes from all
       those famous personalities.
       If this was the case then Homeopathy had been doing this thing for
       a long time, and if it were that successful regarding placebo then
       we would not even have Allopathy today. Not even this, the ancient
       medicines like herbal medicines etc would have been more than
       enough. Why move to even Homeopathy or even Allopathy then?
       Why was there Polio vaccination, hmm? And then there’s a long list
       of ailments which ancient medicines utterly failed to cure and were
       treated only by Allopathy successfully.
       There’s certain objectivity in placebo, but it has been used to
       prove delusion most of the times.
       There used to be a time when humans “believed so hard” that “they
       could have wings”, and many even tried to fly by attaching fake
       wings, “believing hardly” that their belief would make those fake
       wings a “real ones” (i.e. shaping their perception); and then they
       could easily proceed to fly in air. Sadly, this lead to countless
       deaths in the human history. And even if that would have been the
       case then we would not be having airplanes among us today. It shall
       be so easy then just to “believe” that one has wings, and then
       everybody would be flying easily.
       Also, it would be rather simple just to believe that one is full
       and would not proceed to eat something. And we see doing that would
       rather lead to starvation, which is harmful on another level. And
       the list simple goes on.
       But hey, then there are further arguments on “believing rightly”
       and this would lead to infinite arguments for the sake of
       arguments, as in all this has happened because “belief” was not
       carried out rightly or a belief was not believed correctly; and
       this would further aggravate things up as in which one is the
       “right” way of believing, further leading into infinite dialogues.
       We can see countless religions a result of “believing rightly”.
       A belief is merely a very subjective thing. I would rather say the
       opposite, to that of what the write has mentioned, and that is
       perceptions shapes beliefs. A belief in its very nature is purely
       subjective.
       We have made other material tools because we need them. For
       instance an eye is a tool to see things and we need it to see
       light. If we would have been able to see light without eyes, then
       why do we have eyes in the very first place? Same goes for our
       arms, legs, body and other material tools. But let us not forget
       that humans need tools, which are our extensions.
       Let us not forget that one has to see the picture in totality,
       which would eventually take us to a certain objectivity. And that
       objectivity will be purely without subjectivities.
       Reply
          + Rich
            August 2, 2013 at 12:54 pm
            Reality is an illusion.
            The blind spot test is one way to become aware. A reality
            illusion of a complete computer screen is thought to be seen,
            but the eyes have blind spots so the information is already
            incomplete. The missing information is added.
            See: Online Eye Test: Find Your Blind Spot in Each Eye! –
            http://tinyurl.com/l9znwgh
            The senses filter.
            Reply
               o Predrag Lozanovski
                 August 3, 2013 at 10:15 am
                 @Tahir, I think you’re confusing the areas where belief
                 does or doesn’t work. For example, you’ll never turn into
                 an elephant no matter how hard you believe to be one. But
                 you will very well overcome an ailment – or at least
                 alleviate its symptoms or pains and/or stimulate your
                 recovery. Yet the most important part – which again is
                 most difficult to prove or demostrate – is the fact that
                 by means of belief you can always prevent yourself from
                 becoming ill, especially from those new and mostly
                 preconceived “ailments” like arising of cancer as a
                 result of smoking.
                 So, belief works with all those things that exist as a
                 result of our BELIEVING IN THEIR EXISTENCE.
                 Sure you can also change some things within this
                 “Reality” that seem impossible to change, like flying for
                 instance. But to do that, you’ve got to alter some parts
                 of “Reality” as well – as it’s the case in your dreams.
                 You can’t fly as long as you accept all those physical
                 laws that are congruent parts of our “Reality”. As long
                 as you believe in those physical laws, you’re bound to
                 the earth. The problem seems to be our BELIEVING. Insects
                 like May-beetles for instance, DON’T believe in physical
                 laws, that’s why they’re able to fly. If they believed in
                 those physical laws, they’d “know” that their bodies are
                 not shaped aero-dynamically, so they would never even try
                 to fly. So, if you want to go further than just overcome
                 some problems that are easy to solve – like not becoming
                 ill of something, Millions of people get ill from –
                 you’ve got to alter your own system of beliefs, thusby
                 sort of producing “your own Reality”. If you do that,
                 you’ll realize that some things will become possible for
                 you, and other will not. And then you’ll realize that
                 your own intervention within this widely accepted
                 “Reality” is limmited. As a final result you’ll probably
                 find out that your ultimate success should be TO CREATE
                 YOUR OWN REALITY that is BASICALLY DIFFERENT THAN THIS
                 ABNORMAL ONE, where we exist as long as we believe in it
                 the way it is. In other words, you’ll be able to overcome
                 this “Reality” when you stop believing that it was
                 created by God or is an unchangable course of Evolution.
                 Your final and ultimate developent starts when you
                 realize that “God” or “Evolution” are NOT EXTERN, but
                 WITHIN YOU. You are the Creator of your own NEW AND
                 INDIVIDUAL Reality and partly an executor within this OLD
                 AND COLLECTIVE “Reality”. :)
                 Reply
   13. johnsonwi10
       July 29, 2013 at 11:57 pm
       Wow, can it really be possible? From Statistics class lectures, it
       said that the placebo effect worked more than half the time, but I
       didn’t know it was this serious. I wonder if I can finally end my
       depression and pain from simply believing. Why aren’t we funding
       research on this? The potentialities are LIMITLESS!!! Or are we
       funding this?
       Reply
          + Rich
            July 30, 2013 at 2:49 am
            Why aren’t we funding research on this?
            In all kindness:
            Everything which is needed, you already have!
            Use (focus with) information which creates the end-result of
            that which you do want only, in the now.
            A) ”Reality is merely an illusion, albeit a very persistent
            one.” – Albert Einstein
            http://tinyurl.com/5kkgm
            &
            Are We Living in a Holographic Universe? This May Be the
            Greatest Revolution of the 21st Century
            http://tinyurl.com/6b7wdlf
            Adjusting Albert Einstein’s quote: “Reality is merely an
            illusion, albeit a very persistent holographic one”
            &
            B) Man sieht nur das, was man weiß.
            You only see what you know. (One only experiences what one
            knows).
            Johann Wolfgang von Goethe
            http://tinyurl.com/mvk4c2d
            &
            Bible: New International Version (©2011)
            In the beginning was the Word, and the Word was with God, and
            the Word was God.
            http://tinyurl.com/p7vg5xs
            That which one ‘knows’, in general, is a multitude of
            concepts, for one, known as a language. Aka ‘the word’.
            Use concepts (words/language/information) and energy assumes
            holographic form variations and manifests as a holographic
            reflection relative to the information. Energy is free from
            judging, cultural codes etc. etc. Energy just assume
            holographic form variations which manifest as realities.
            See:
            Numerical cognition without words: evidence from Amazonia”.
            In: Science Express, 10.1126/science.1094492 (2004)
            “…Members of the Pirahã tribe use a “one-two-many” system of
            counting. I ask whether speakers of this innumerate language
            can appreciate larger numerosities without the benefit of
            words to encode them. This addresses the classic Whorfian
            question about whether language can determine thought. Results
            of numerical tasks with varying cognitive demands show that
            numerical cognition is clearly affected by the lack of a
            counting system in the language. …”
            http://tinyurl.com/mwuujnc
            The persons who are deemed to be the Pirahã tribe are also
            ‘co-creators’ and use their concepts. Energy still just
            assumes holographic form variations and manifests as a
            holographic reflection relative to this information. The
            holographic reflection of the persons who are deemed to be the
            Pirahã tribe manifests as “one-two-many”. Four, five, six
            doesn’t manifest as this information is lacking and cannot be
            used to focus with.
            Information can also be used to create a “Wild goose chase”.
            Shifting the focus via deduction and using ‘word
            camouflage”.le
            An exemple
            The persons who are producing are ‘producers’. The persons who
            are consuming are ‘consumers’.
            Statement:
            “The producers are optimistic and the consumers are
            pessimistic.”
            The concept ‘person’ is deducted and the Wild Goose chase is
            created.
            After all a person who produces also consumes and should the
            statement belong to one’s belief system, a person is both
            ‘optimistic’ and ‘pessimistic’, simultaneously.
            Energy still just assume holographic form variations which
            manifest as realities, with in consciousness.
            1) In the awake state of consciousness it is possible to
            experience walking down a beach, meeting people, see
            reflections in the water etc..
            2) In the dream state of consciousness it is possible to
            experience walking down a beach, meeting people, see
            reflections in the water etc..
            3) In the imagining state of consciousness it is possible to
            experience walking down a beach, meeting people, see
            reflections in the water etc..
            All these alternative states of consciousness feel ‘real’ and
            form realities. Yet from the dream state of consciousness we
            know, only we personally can be the co-creator of the
            reality-hologram (illusion). And it is still energy which
            assumes holographic form variations and manifests as a
            holographic reflection relative to the information.
            It is all ‘in the mind’.
            Reply
          + Predrag Lozanovski
            August 5, 2013 at 6:41 pm
            @johnsonwi10: Ending your depression and pain by simply
            believing should be the easy part, any good Psychologist could
            help you at it. It need not even be a Psychologist, any gifted
            person could do it as well. The crucial part is your reaction.
            If you believe, anything within the sphere of believing is
            possible. Let me tell you this: If a doctor or a priest tell
            you that you’re ill or sinfull, you can’t but BELIEVE THEM, so
            you’re ill or sinfull, because you believe that you are. When
            that doctor or priest tells you that you’re cured or your sins
            are forgiven, you BELIEVE THEM again, since you can’t find it
            out yourself, so you’re cured or forgiven because YOU BELIEVE
            IT. So, belief works within the sphere of Authorities that we
            put our trust in – doctors, scientists, priests, “God”…
            Knowing that and the fact that your body is best equipped with
            every thing that is neccessery to make you ill or to heal you,
            you all of a sudden realize that EVERY THING DEPENDS ON YOU
            AND YOUR BELIEVING.
            This works even if you believe in some higher powers – like
            God for instance. When you’re in a trouble or ill from a
            dangerous ailment you can believe that God can help you – and
            if you believe it hard enough, YOU WILL be cured. As a matter
            of fact you’ll ALWAYS get healed by YOUR OWN BELIEVING, not
            because an external instance has helped you, but it’s still up
            to you to define WHO helped you. If you’re very young you will
            probably believe that God had helped you. If you’re old enough
            to understand that YOU ALONE ARE ALMOST TOTALLY SUFFICIENT TO
            MAKE YOURSELF ILL OR TO HEAL YOURSELF – you’ll understand that
            IT WAS YOU who helped you.
            Of course there is one more option that you can choose to
            believe in, although it’s pretty questionable and far from
            being proven by anyone. That option involves your FUTURE “ME”.
            It is possible that at a future moment we all will be able to
            intervene in our own Past, in order to save ourselves from
            some personal disasters. Maybe only some people will be able
            to do that, but it doesn’t matter now, the point is that it is
            possible for you in future to act back in time in order to
            save yourself from something. You’re probably able to remind
            yourself of some situations when you evaded a danger without
            knowing how or why that happened. As for me, I’ve been in
            several situations when I got rescued from something in a way
            that leaves the option open for my future ME to have
            intervened to my favour – other options however not excluded.
            Back to your question: Depression and pain are no real
            obstacles for your belief. You can handle them just like that.
            Although I’m not a believer, let me remind you of Jesus’
            words: “If you have faith the size of a small mustard seed,
            you’ll say to this mountain ‘Move over!’ – and it will obey.”
            I’m not referring to the religious faith in God. I’m referring
            to FAITH IN GENERAL, since religious faith is just one form of
            FAITH or BELIEVING. So one of the “things” you’ve got to do is
            believe that things are not as they seem. What we see is what
            WE HAVE BEEN TAUGHT TO BE TRUE. Some of it corresponds with
            Reality, while many things are far from being real – and yet
            we believe in them. So if you ask me, I’d advice you to first
            of all realize that YOU ARE THE MOST IMPORTANT “THING” IN THE
            WHOLE “UNIVERSE” – which will make it easy for you to develop
            your faith or your self-confidance. That as a start. Every
            thing else will follow as a normal and logical advancement of
            your personal growth. Not saying that every thing will be ok –
            but in spite of all your future problems – or yet better:
            THANKS TO THEM you’ll become more and more effective,
            gradually overcoming this present so-called “Reality” and
            upgrading your own personal Reality.
            Reply
   14. Rich
       July 26, 2013 at 1:47 am
       INVENTOR OF ADHD’S DEATHBED CONFESSION: “ADHD IS A FICTITIOUS
       DISEASE”
       http://tinyurl.com/b3y7uvc
       Not only does the placebo effect work to create a cure but also to
       create the disease.
       There is nothing either good or bad but thinking makes it so.
       William Shakespeare
       http://tinyurl.com/4fom4jc
       Of course, in order to think ‘what ever’ one needs the concepts. It
       be ‘good’, ‘bad’, ‘disease’, ‘cure’, ‘ADHD’, etc.
       No concepts and energy will not assume a form and remain formless.
       Kindly refer to the definition.
       Reply
   15. Rich
       July 25, 2013 at 8:03 am
       I don’t believe in mathematics.
       Quoted by Carl Seelig. Albert Einstein.
       http://tinyurl.com/kbxm5z4
       Albert Einstein negates/nullifies mathematics; he is not solving
       mathematical problems, but creating the problems and the solutions.
       After all, mathematics is also a holographic energy form variation
       manifestation, within consciousness.
       Albert Einstein e=mc^2 is about ‘energy’. It is not about
       ‘light-speed’. Light-speed is not energy, but also a holographic
       energy form variation manifestation. Yet using the information
       ‘light-speed’ to focus with will have energy act according the the
       definition.
       Light-speed is also a ‘belief’ as is the ‘placebo-effect’.
       It is impossible for energy to go ‘faster’ than itself. There is no
       need to either! Please see definition.
       Definition:
       “Everything is a holographic energy form variation manifestation,
       within consciousness, by which energy assumes the holographic form
       variation and manifests as a holographic reflection relative to the
       information* which is in use to focus with and in doing so
       co-create with.”
       Reply
   16. Rich
       July 24, 2013 at 3:10 am
       Is Economics a Science or a Religion?
       Bloomberg – http://tinyurl.com/oalfl5g
       Economics is also information which is ‘believed’ as are all other
       sciences, academic and otherwise, and energy will plain and simply
       assume holographic form variations which will manifest as a
       reality.
       Reply
   17. Rich
       July 24, 2013 at 1:53 am
       A definition which one can learn by heart. After all, one can read
       all one wants, go to lectures all one wants, forgetting, is no
       matter what, a human quality.
       Definition:
       “Everything is a holographic energy form variation manifestation,
       within consciousness, by which energy assumes the holographic form
       variation and manifests as a holographic reflection relative to the
       information* which is in use to focus with and in doing so
       co-create with.”
       *Information is factor X.
       Change the information and energy assumes an alternative form
       variation which manifests relative to the alternative information.
       “We are not the cool observers of the world, but its “passionate
       creators” — we are all poets and the world is our metaphor.” –
       Roger S. Jones
       Measurement Problem – Reality is an Illusion
       YouTube
       http://tinyurl.com/cglc5ve
       In this YouTube video replace ‘observer’ with the person who
       co-creates by focusing information, and the puzzle will fall into
       place.
       Reality is holographic, but English, for one, is lacking the
       holographic quality of energy in the concepts which form the
       English language.
       By focusing information even if it is lacking the holographic
       quality still has energy act according to the definition above.
       Reply
   18. Rich
       July 23, 2013 at 2:48 am
       The following url gives a visualisation of how information has
       energy assume form variations.
       Water, Consciousness & Intent: Dr. Masaru Emoto
       https://www.youtube.com/watch?v=tAvzsjcBtx8
       Reply
   19. Predrag Lozanovski
       July 22, 2013 at 2:18 pm
       GREAT ARTICLE! (I knew about those facts long time ago, my
       favourite notions sound: “our body is the most powerful factory”
       and “the way it (an eilment) comes, the way it goes”. I haven’t
       been seriously ill for over 35 years. During that time I’ve had
       only 3 tooth extractions and a chirurgical intervention on
       hemorrhoides.)
       Reply
   20. Jeremy
       July 22, 2013 at 12:05 pm
       Well, I dont know of some of the things that bother me, only that I
       experience pain in a certain area and it has been diagnosed, after
       almost a year and a million dollars woth of tests and drugs as “I
       dont know what ails you!” So I meditate on a daily basis that my
       body is healthy and will stay that way…
       Reply
   21. Rod Dalitz
       July 21, 2013 at 5:01 pm
       This is also the case for homeopathy.
       Reply
   22. waltinseattle
       July 21, 2013 at 4:18 pm
       “hyperactive children who are given a “dose extender” IN FULL
       KNOWLEDGE THAT it is an INACTIVE PILL ” can reduce their regular
       meficstion by half with no ill effects” from Slights of Mind by
       Strphen Macknik and Susana Martinez-Conde…neuroscientists both…pg
       210
       btw there is no mind brain body separatness. all one “Thing”..a
       thing that include “process” as well as “objects.”
       Reply

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Could an app replicate the placebo effect?

   New research shows deception isn't needed to induce healing effects
   with fake meds

   By Adrianne Jeffries on May 14, 2013 11:00 am @adrjeffries 81Comments

   Don't miss stories Follow The Verge
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   medical cupcakes

   Daniel Jacobs believes in the placebo effect, the well-documented but
   not well-understood phenomenon in which sick patients sometimes feel
   the same healing effects from swallowing a sugar pill that they would
   from taking a real one. He believes in it so strongly that he doesn’t
   believe people even need to take a pill in order to produce a positive
   placebo effect; an app with a picture of a pill will do.

   That’s the basis of his startup, Placebo Effect, which is raising
   $50,000 through the crowdfunding site Indiegogo to build his prototype
   into an iPhone app that he says can harness the placebo effect in order
   to help people make positive changes in their lives, such as feeling
   happier or quitting smoking.
     __________________________________________________________________

   "New research shows deception may not be necessary for the placebo
   effect"

   The app offers a variety of "placebos," including images of a pill, a
   magic wand, a communion wafer, and other options. "Placebo pills are
   actually chosen often. About 12 percent of people in our testing choose
   pills," he said. "The reason for that probably is that in our society,
   we feel that pills work really well."

   He’s done limited testing with good results, he said, and plans to do
   more. So far, 39 people self-reported an average of 31 percent increase
   in the effect they were trying to create in their lives, for example
   joy, energy, physical healing, or love, after one use. Seven users
   reported no change, and one person reported a negative change and did
   not complete the trial.

   Jacobs’ idea may sound a bit bogus, especially since it is widely
   believed that the placebo effect only works if the patient believes he
   or she is taking a real treatment. This perceived need for deception is
   part of the reason doctors don’t prescribe placebos, despite the fact
   that they can occasionally work as well as FDA-approved treatments for
   some conditions.

              IFRAME: http://www.youtube.com/embed/3J73TEnPj5w

   However, new research suggests deception may not be necessary to induce
   a placebo effect. In 2010, researchers from Harvard Medical School and
   other institutions did a study on patients diagnosed with Irritable
   Bowel Syndrome (IBS). One group received no treatment, while the other
   patients were told they’d be taking inactive drugs and told that
   placebos can have healing effects. To drive the point home, the fake
   drugs were placed in bottles labeled "placebo pills."

   The patients who knew they were taking placebo pills reported twice as
   much relief as the control group. The placebo had healing effects
   comparable to some of the best real IBS drugs. "Our results challenge
   ‘the conventional wisdom’ that placebo effects require ‘intentional
   ignorance,’" the researchers wrote.

   "Placebos are used to test treatments, but in the future they could be
   the treatment"

   If placebos could be effectively prescribed without the need to lie to
   patients, it would be revolutionary. Placebos are cheaper and safer
   than many treatments. Studies have shown placebos to be 75 percent as
   effective as antidepressants. Fake surgeries have been shown to be just
   as effective as real surgeries in treating Parkinson’s. Today placebos
   are used to test treatments, but in the future they could be the
   treatment. Some doctors are already prescribing placebos this way. "We
   should be using every tool in the box," Ted Kaptchuk, a Harvard
   professor, leading placebo effect researcher, and alternative medicine
   expert, told Harvard Magazine.

   Kaptchuk worked on the IBS study that showed a placebo effect even when
   patients knew they were taking a placebo. He now runs the Program in
   Placebo Studies and the Therapeutic Encounter (PiPS) at Beth Israel
   Deaconess Medical Center, a group dedicated to placebo research. The
   placebo effect varies from person to person, and some may be
   genetically predisposed to it. The type of placebo and the condition
   also matter: pills work better for insomnia, studies have found, while
   injections work better for pain.

   It's also important not to cause the nocebo effect, in which patients
   suffer the same harmful side effects associated with a real medication,
   for example, even when taking the fake version. It works like the
   placebo effect but induces negative reactions instead of positive ones.
   "Placebo" translates to "I will please" in Latin. "Nocebo" translates
   to "I will harm."

   Kaptchuk and his colleagues have plenty of critics within the FDA, the
   pharmaceutical industry, and academia. A group of Danish researchers
   conducted a meta-analysis in 2001 and again in 2004, concluding that
   there is "little evidence in general that placebos had powerful
   clinical effects."

   It’s also unclear how much of the measured effects are due to the
   placebo effect, and how much might be due to other factors. It’s been
   suggested that patients experiencing improvement could be have a
   reporting bias, for example, that skews in favor of the result they
   believe will please their doctors.

   ""This is extremely effective.""

   As to whether the placebo effect can be simulated by an app, more
   research is needed there too. (Due to the lack of empirical evidence,
   Kaptchuk declined to comment, via his program manager, on whether an
   app could induce the placebo effect.)

   "What we’re not saying here is, ‘stop taking your antidepressants and
   to then do this instead,’" Jacobs said. "What we are saying is that the
   literature shows, and our own internal studies, and later on, clinical
   trials that we will surely do, that this is extremely effective. It
   would be wonderful if you could complement this with whatever else
   you’re doing in life."
     * Image Credit Clever Cupcakes (Flickr)
     * Related Items health daniel jacobs indiegogo crowdfunding placebo
       effect nocebo effect ted kaptchuk program in placebo studies and
       the therapeutic encounter

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11 Surprising Facts About Placebos

   Joseph Brownstein, LiveScience Contributor
   Date: 03 June 2013 Time: 08:00 AM ET

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     * Introduction Intro CREDIT: Brian Hoskins | Stock Xchng Pills
     * Early placebo research was done in the 18th century for consumer
       protection. A woman holds two aspirin in her hand. 11 CREDIT: Pills
       photo via Shutterstock aspirin-pills-water-120910
     * Even real treatments benefit from the placebo effect. A bottle of
       prescription pills 10 CREDIT: Prescription photo via Shutterstock
       prescription-drug-130328
     * "Placebo" and "the placebo effect" refer to different things. 9
       Assorted Pharmaceutical Drugs
       Credit: Dreamstime
     * There is a "nocebo" effect. A woman holds her aching head 8 CREDIT:
       Headache photo via Shutterstock woman-headache-130415
     * Many clinical trials no longer include placebos. doctor's office,
       appointment, physical 7 CREDIT: Doctor's visit photo via
       Shutterstock Doctor's visit
     * Placebos have a long-term, demonstrated effect in relieving pain.
       fibromyalgia 6 CREDIT: Yuri Arcurs | shutterstock fibromyalgia,
       neck pain
       Tender points on the neck are one sign of fibromyalgia
     * Scientists don't know if certain groups of people are more
       susceptible to placebos. A bottle of pills 5 CREDIT: Pills photo
       via Shutterstock pill-bottle-120619
     * The placebo effect is actually several effects.
       pills-natural-101014-02 4 CREDIT: Alita Bobrov | Dreamstime Pills
       Natural
     * Psychiatric illnesses are among the conditions most susceptible to
       placebos. brain cells, neurons 3 CREDIT: Dreamstime Brain
       The brain is made up of an inconceivable number of cells.
     * Not all placebos are created equal. drugs 2 CREDIT:
       Shutterstock.com drugs
       Drugs, when taken in combination, can cause severe side effects.
     * Placebo does not equal being duped. 1 FDA Issues Serious Reality
       Check on Diet Pills
       Photo taken by Steve Knight (stevekrh19). There are no usage
       restrictions for this photo

   The placebo effect plays a central role in doctors' understanding of
   whether medications work.

   The effects of a placebo, or "dummy," treatment cannot come from the
   actual treatment itself. In other words, the placebo effect explains
   why people report feeling better when they think they are taking
   medicine, but aren't actually receiving the treatment. (The word
   placebo comes from the Latin for "I will please.")

   The placebo effect can help explain why drugs and other treatments with
   no value can seem to work, and therefore, why some treatments pass
   muster while others do not.

   However, the placebo effect itself remains mysterious. Doctors still
   have questions about how it operates, and why its effect can be large,
   small or nonexistent for a given treatment or patient.

   The following pages share some of the history, knowledge and
   misconceptions about the placebo effect.

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   [psiteeny.gif]

Placebo Effects

   Believing in something often helps to make it work. This is called the
   placebo effect. A placebo (pronounced pluh-SEE-bo) is literally a
   "pleasing thing." The word usually refers to a sugar pill or fake
   medicine. However, the phrase "placebo effect" has come to mean much
   more. To most psychology researchers, the phrase placebo effect now
   refers to any situation in which a person's belief in a treatment
   causes the treatment to work (Critelli & Neumann, 1984).

   What are placebo effects? Are they imaginary?

   Placebo effects, defined this way, are not imaginary. They are genuine
   changes produced by a person's knowledge or belief in a manipulation.
   For example, if you wore a certain cologne which made you feel more
   attractive, you might act more attractive and be more attractive. This
   would be a placebo effect if your belief affected your behavior, but
   the cologne by itself had no real effect. To determine whether that was
   the case, the placebo effect would have to be controlled.

   How do you control a placebo effect?

   When testing the effects of a new medicine, researchers must give the
   control group a placebo-a realistic-looking "fake" which contains no
   active ingredient. The experimental group gets the real medicine, the
   control group gets the placebo. Both groups think they are getting a
   real medicine. This way the researchers can tell if the medicine has
   any effect beyond the expected placebo effect, which should be present
   equally in both groups.

   Students have no trouble understanding this idea, yet many still miss
   this question:

   1) How do you control the placebo effect?

   a) give the control group an experimental treatment

   b) give the experimental group a "sugar pill"

   c) create a placebo effect in the control group

   d) make sure nobody gets a placebo

   The correct answer is "c." To some students that sounds wrong. If it
   sounds wrong to you, study this concept until you understand it. A
   researcher tries to create a placebo effect in the control group to
   equalize the placebo effect in the two groups. That removes the placebo
   effect as a confounded variable, because it is not a difference between
   groups. (In other words, both groups must believe they are receiving a
   genuine treatment, to equalize the placebo effect and remove it as a
   confounding variable.)

   What is a single-blind design?

   An experimental design in which subjects do not know whether they are
   receiving a placebo treatment or a real treatment is called a
   single-blind design. The subjects are blind to which treatment they are
   receiving, although the experimenter may be aware of which they are
   getting.

   Prev page | T of C | Next page
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     *  Discussion
     *  Analysis

   Placebo Effect
   Sheldon: Do you believe in the placebo effect?
   Amy: Of course I do. There have been many studies proving its validity.
   Sheldon: Great. Now, this may look like a Tic Tac, but it is really a
   powerful medication specifically designed to cure your illness as well
   as freshen your breath.
   -- The Big Bang Theory

   The placebo effect is where a patient thinks that a 'medicine' is
   healing them, even though it doesn't have an actual medical effect. The
   most common use is in drug trials, in which a control group is given a
   placebo, to compare the effects in case the drug actually is only
   effective due to the placebo effect, or is even worse.

   One difference between fiction and reality is that, unlike in fiction,
   real placebos often continue to have an effect even if the user finds
   out it's a placebo - the action of taking the "drug" is usually enough
   to fool the body.

   The opposite is the nocebo effect, in which someone believes something
   is hurting them or making them sick, when it's really not. This could
   even kill them, as Your Mind Makes It Real.

   See Magic Feather in terms of the plot. A more realistic version of
   Clap Your Hands If You Believe.
     __________________________________________________________________

Examples:

       open/close all folders

       Anime and Manga
     * One chapter of Sayonara, Zetsubou-Sensei has a field day with this
       trope, including Nozomu taking a placebo drug and breaking out in
       hives from the percieved side effects, Stalker with a Crush Matoi
       forcing Nozomu to take a fake Love Pill, only for the effect to
       work on her instead when she's the only one convinced that it
       worked, and Nozomu eventually getting fake surgery performed on him
       to get rid of the fake side effects from the fake drug he took at
       the start, and ending up convinced that he's been turned into an
       android.
          + The chapter also throws some Leaning on the Fourth Wall into
            the mix, by introducing a sticker that, if you stick it to a
            manga, makes it six times funnier. Immediately the sticker
            starts showing up more and more, until the last two pages are
            covered in them.

       Film
     * In Eurotrip, two of the characters order brownies at an Amsterdam
       bakery run by a Dreadlock Rasta. They immediately become stoned
       beyond belief...until the Dreadlock Rasta calmly informs them that
       they're not hash brownies.
     * The protagonist of Matchstick Men, who has severe OCD, is given a
       packet of pills by his psychiatrist that apparently heals him.
       Around the same time, he starts bonding with his long-lost
       daughter. He eventually learns that the pills are just soy
       menopause supplements, and that bonding with his daughter has given
       his life meaning and helped him overcome his neurosis.
     * The Birdcage: Armand's "Pirin tablets" -- he seems to think they're
       some kind of powerful anti-anxiety medication; they are in fact
       Aspirin with two letters scraped off. They seem to do the job,
       though.
     * In SpaceJam, the Tune Squad has completely given up hope of winning
       their basketball game against the Monstars until Bugs Bunny gives
       them 'Michael's Secret Stuff', which buffs them up and gives them
       the confidence to get back in the game. Of course, the real secret
       is that it is just water.
     * Subverted in The Exorcist. In one scene, a priest douses the
       demon-posessed protagonist with tap water and claims that it's holy
       water, but the protagonist screams in pain anyway. Later, though,
       it's implied that the demon only pretended to be fooled so that the
       priests would think that the "possession" was purely psychological
       and wouldn't try to exorcise it. When the priests douse the
       protagonist with real holy water in the climactic exorcism scene,
       the screams are real and the water leaves visible burns.
     * An inadvertent psychotherapy version appears in What About Bob?:
       Bob's new therapist gives him a copy of his book Baby Steps, which
       is about setting small, attainable goals. Bob completely misses the
       point and thinks that he has to physically take small steps
       wherever he goes. However, Bob's focus on taking "baby steps" when
       he gets nervous helps distract him from his fears and allows him to
       do things he wasn't able to do before.

       Literature
     * In It, it is revealed that Eddie Kaspbrak's asthma is
       psychosomatic, and his medication is a placebo.
     * Inverted by Captain Underpants, who thinks his powers are
       neutralized if he's sprayed with spray starch.

       Live Action TV
     * Star Trek: The Original Series At the end of Mudd's Women.
     * The Red Green Show had an episode where the lodge members were part
       of a test-market for an energy bar, making them very active and
       becoming addicted. When the test batch ran out, they reverted back
       to normal, only for Harold to reveal all they got was a basic
       granola bar to gauge product interest, due to the real stuff being
       too dangerous. Red, taking this as proof of the strength of his
       mind, salvages one of the test sample bars and tells his wife at
       home to wait up that night.
     * In an episode of Frasier, Niles eats a normal brownie thinking it's
       a pot brownie, with the reverse situation for Martin. Hilarity
       Ensues.
     * One time on Mash they run out of morphine so they give the patients
       sugar pills telling them it's a strong painkiller. It works.
          + On the B-plot of that episode, they're experiencing a heat
            wave that has everyone miserable. They give Klinger some of
            the sugar pills claiming they're some sort of new drug that
            will allow him to feel cooler. He spends the rest of the
            episode in his regular uniform while everyone else is wearing
            undershirts.
     * The Suite Life on Deck: Bailey uses a placebo to raise London's
       intelligence. Subverted in that after realizing that it's a
       placebo, London returns to normal. Then she takes another placebo.
     * On The Big Bang Theory, Raj is unable to talk to women unless he's
       drunk. In "The Terminator Decoupling," the guys are on a train when
       they discover that Summer Glau is in the same car, and they all try
       to hit on her. Raj drinks copious amounts of beer before going over
       to talk with her, and she actually seems to like him. Then Howard
       walks over and informs him that it was non-alcoholic beer. He clams
       up and walks away without another word.
     * Referred to when the MythBusters tested seasickness cures. To be
       certain that Adam and Grant weren't subconsciously skewing the test
       results, Jamie gave each of them an "over-the-counter medicine"
       that was actually a vitamin pill. (Grant fell for the placebo, but
       Adam got sick just as fast as in the other tests.)
     * In The Next Mutation, the Turtles have a recurring team of foes
       that once used a magic formula to enhance their abilities. The
       effect ended when the turtles pointed out the 'magic' was just a
       placebo.
     * Used when NewsRadio parodied Flowers for Algernon. Joe makes
       Matthew a "Smart Drink", which works until Matthew gets smart
       enough to realise it's only working because he thinks it will.
       Matthew: It's like when Wile E Coyote runs off a cliff. He can stay
       standing in mid-air until he looks down.
     * Penn And Tellers Bullshit episode "Yoga, Tantric Sex, Etc."
       featured a man trying to explain why herbs work for some people and
       not for others. Penn summed up the entire argument in one sentence.
       Penn: If you believe they work they work, if you don't they don't.
       You hardly ever hear that about penicillin.

       Western Animation
     * Dogbert has a placebo that works even when the user knows it's a
       placebo.
          + That, and the people he's giving them to are usually too
            stupid to realize what a placebo is.
     * The Simpsons: The Crazy Cat Lady once regained her sanity thanks to
       a medication but lost it when she learned it was a placebo.
     * In the Handy Manny segment "Fearless Rusty", Lovable Coward Rusty
       is sprinkled with "magic dust" by a local magician, who claimed it
       would make him brave... and he believes it.
     * In one episode of Hey Arnold!, Helga bought an anti-love potion
       that successfully killed her feelings for Arnold only to learn
       later on that it was just grape juice.

       Real Life
     * Chiropractic adjustments are controversial, owing to the fact that
       there's little scientific proof that the person doing an adjustment
       (technically a Doctor of Chiropractic, since they aren't actually
       medical doctors) is doing anything other than basic decompression
       of the spine. But because these 'doctors' are very good at
       convincing people they'll feel better, they do tend to feel better.
     * Acupuncture also has very little proof that it is effective (yes,
       they are able to do studies with needles that look like they are
       inserted, but actually are not), but people really believe that it
       helps them.
     * Therapeutic Touch therapy and it's "Eastern" equivalent, reiki,
       worked through this effect as well - it's so easily debunked that a
       9-year old girl was able to do it, as seen here [external_link.gif]
       .
     * Homeopathy may fool many people due to the placebo effect, despite
       the fact that it would have to utterly violate some of the most
       basic laws of physics and chemistry in order to work.
     * Iridology. [external_link.gif] In the words of The Other Wiki:
       Iris texture is a phenotypical feature which develops during
       gestation and remains unchanged after birth.
     * Pretty much all pseudoscientific "treatments" depend on this. They
       are mostly (not entirely, but mostly) directed toward the relief of
       (chronic) pain, which is one of the most incredibly subjective
       things on the planet to attempt to measure.
     * Guess why the pharmaceutical industry spends more money on
       advertising than research. [external_link.gif]
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   "I can explain."
   by Kas Thomas

Sunday, March 24, 2013

New Patents Aim to Reduce Placebo Effect

   The pharma industry has a big problem on its hands: Placebos are
   getting to be way too effective. Something needs to be done. But what?
   What can you do about placebo response? The old saying "It is what it
   is" would seem to hold true in this case.
   One answer: come up with low-placebo-response study designs, and patent
   them if possible. (And yes, it is possible. But we're getting ahead of
   the story.)
   Placebo effect has always been a problem for drug companies, but it's
   especially a problem for low-efficacy drugs (psych meds, in
   particular). An example of the problem is provided by Eli Lilly. In a
   March 29, 2009 press release announcing the failure of Phase II trials
   involving a new atypical antipsychotic known as LY2140023 monohydrate
   or mGlu2/3, Lilly said:

     In Study HBBI, neither LY2140023 monohydrate, nor the comparator
     molecule olanzapine [Zyprexa], known to be more effective than
     placebo, separated from placebo. In this particular study, Lilly
     observed a greater-than-expected placebo response, which was
     approximately double that historically seen in schizophrenia
     clinical trials. [emphasis added]

   [PlaceboDoctor.png] Fast-forward to August 2012: Lilly throws in the
   towel on mGlu2/3. According to a report in Genetic Engineering and
   Technology News, "Independent futility analysis concluded H8Y-MC-HBBN,
   the second of Lilly's two pivotal Phase III studies, was unlikely to be
   positive in its primary efficacy endpoint if enrolled to completion."
   Lilly is not alone. Rexahn Pharmaceuticals, in November 2011, issued a
   press release about disappointing Phase IIb trials of a new
   antidepressant, Serdaxin, saying: "Results from the study did not
   demonstrate Serdaxin's efficacy compared to placebo measured by the
   Montgomery-Asberg Depression Rating Scale (MADRS). All groups showed an
   approximate 14 point improvement in the protocol defined primary
   endpoint of MADRS."
   In March 2012, AstraZeneca threw in the towel on an adjunctive
   antidepressant, TC-5214, after the drug failed to beat placebo in Phase
   III trials. A news account put the cost of the failure at half a
   billion dollars.
   In December 2011, shares of BioSante Pharmaceutical Inc. slid 77% in a
   single session after the company's experimental gel for promoting
   libido in postmenopausal women failed to perform well against placebo
   in late-stage trials.
   The drug companies say these failures are happening not because their
   drugs are ineffective, but because placebos have recently become more
   effective in clinical trials. (For evidence on increasing placebo
   effectiveness, see yesterday's post, where I showed a graph of placebo
   efficacy in antidepressant trials over a 20-year period.)
   Some idea of the desperation felt by drug companies can be glimpsed in
   this slideshow (alternate link here) by Anastasia Ivanova of the
   Department of Biostatistics, UNC at Chapel Hill, which discusses
   tactics for mitigating high placebo response. The Final Solution?
   Something called The Sequential Parallel Comparison Design.
   SPCD is a cascading (multi-phase) protocol design. In the canonical
   two-phase version, you start with a larger-than-usual group of placebo
   subjects relative to non-placebo subjects. In phase one, you run the
   trial as usual, but at the end, placebo non-responders are randomized
   into a second phase of the study (which, like the first phase, uses a
   placebo control arm and a study arm). SPCD differs from the usual
   "placebo run-in" design in that it doesn't actually eliminate placebo
   responders from the overall study. Instead, it keeps their results, so
   that when the phase-two placebo group's data are added in, they
   effectively dilute the higher phase-one placebo results. The
   assumption, of course, is that placebo non-responders will be
   non-responsive to placebo in phase two after having been identified as
   non-responders in phase one. In industry argot, there will be
   carry-over of (non)effect from placebo phase one to placebo phase two.
   [PlaceboSPCDProtocol.png]
   This bit of chicanery (I don't know what else to call it) seems
   pointless until you do the math. The Ivanova slideshow explains it in
   some detail, but basically, if you optimize the ratio of placebo to
   study-arm subjects properly, you end up increasing the overall power of
   the study while keeping placebo response minimized. This translates to
   big bucks for pharma companies, who strive mightily to keep the cost of
   drug trials down by enrolling only as many subjects as might be needed
   to give the study the desired power. In other words, maximizing study
   power per enrollee is key. And SPCD does that.
   SPCD was first introduced in the literature in a paper by Fava et al.,
   Psychother Psychosom. 2003 May-Jun;72(3):115-27, with the interesting
   title "The problem of the placebo response in clinical trials for
   psychiatric disorders: culprits, possible remedies, and a novel study
   design approach." The title is interesting in that it paints placebo
   response as an evil (complete with cuplrits). In this paper, Maurizio
   Fava and his colleagues point to possible causes of increasing placebo
   response that have been considered by others ("diagnostic
   misclassification, issues concerning inclusion/exclusion criteria,
   outcome measures' lack of sensitivity to change, measurement errors,
   poor quality of data entry and verification, waxing and waning of the
   natural course of illness, regression toward the mean phenomenon,
   patient and clinician expectations about the trial, study design
   issues, non-specific therapeutic effects, and high attrition"),
   glossing over the most obvious possibility, which is that paid research
   subjects (for-hire "volunteers"), who are desperate, in many cases, to
   obtain free medical care, are only too willing to tell researchers
   whatever they want to hear about whatever useless palliative is given
   them. But then Fava and his coauthors make the baffling statement:
   "Thus far, there has been no attempt to develop new study designs aimed
   at reducing the placebo effect." They go on to present SPCD as a more
   or less revolutionary advance in the quest to quelch placebo effect.
   Up until this point in science, I don't think there had ever been any
   discussion, in a scientific paper, of a need to attack placebo effect
   as something bothersome, something that interferes with scientific
   progress, something that needs to be guarded against vigilantly like
   Swine Flu. The whole idea that placebo effect is getting in the way of
   producing meaningful results is repugnant, I think, to anyone with
   scientific training.
   What's even more repugnant, however, is that Fava's group didn't stop
   with a mere paper in Psychotherapy and Psychosomatics. They went on to
   apply for, and obtain, U.S. patents on SPCD (on behalf of The General
   Hospital Corporation of Boston). The relevant U.S. patent numbers are
   7,647,235; 7,840,419; 7,983,936; 8,145,504; 8,145,505, and 8,219,41,
   the most recent of which was granted July 2012. You can look them up on
   Google Patents.
   The patents begin with the statement: "A method and system for
   performing a clinical trial having a reduced placebo effect is
   disclosed." Incredibly, the whole point of the invention is to mitigate
   (if not actually defeat) the placebo effect. I don't know if anybody
   else sees this as disturbing. To me it's repulsive.
   If you're interested in licensing the patents, RCT Logic will be happy
   to talk to you about it. Download their white paper and slides. Or just
   visit the website.
   Have antidepressants and other drugs now become so miserably
   ineffective, so hopelessly useless in clinical trials, that we need to
   redesign our scientific protocols in such a way as to defeat placebo
   effect? Are we now to view placebo effect as something that needs to be
   made to go away by protocol-fudging? If so, it puts us in a new
   scientific era indeed.
   But that's where we are, apparently. Welcome to the new world of wonder
   drugs. And pass the Tic-Tacs.
   Posted by Kas Thomas at 12:30 AM
   Email ThisBlogThis!Share to TwitterShare to Facebook

14 comments:

    1. [anon36.png]
       Stephen Senn4:02 PM
       The statisticians involved, at least, ought to know better. 1.They
       are assuming that placebo response is genuine and not just
       regression to the mean (the latter is usually grossly
       underestimated). 2. they are assuming that it is reproducible and
       not transient. 3. they are assuming that the FDA is asleep. If the
       Agency is not dozing they will make them market the drug as being
       only suitable for those who have a proven inability to respond to
       placebo. That should sort them out.
       ReplyDelete
    2. [anon36.png]
       Anonymous8:53 PM
       Could you expand please, on why it is repugnant to attempt to lower
       the placebo response? I've heard this before, and I'm genuinely
       interested as to why this is a problem. I see it as a
       signal-detection issue where solving it may have consequences for
       generalizability etc. I don't really see it as a moral issue, but
       there's every chance I'm missing something?
       As an aside, it strikes me that best design to test a new drug
       would be one where *no-one* knows they are receiving it. Completely
       unethical of course, but we could be guaranteed that any observed
       effect (positive and negative) was actually due to biologically
       induced change - rather than expectation, demand characteristics
       etc. Thus, eliminating the placebo effect would be extremely useful
       here, if we care about knowing the true harms and benefits of the
       drug in question.
       P.s., I'm not psych meds qualify as low-efficacy treatments.
       http://www.ncbi.nlm.nih.gov/pubmed/22297588
       Paul
       ReplyDelete
    3. [anon36.png]
       Stephen Senn6:46 AM
       Paul, if you take the point of view that the practical question is
       to see how a drug improves the situation beyond what would normally
       happen then it seems appropriate to have as a control what would
       normally happen. What is labelled placebo response is in any case
       in most cases just regression to the mean. I regard all this
       placebo response stuff as just so much junk science. See
       http://eprints.gla.ac.uk/8107/1/id8107.pdf and also
       Kienle, G. S. and H. Kiene (1997). "The powerful placebo effect:
       fact or fiction?" Journal of Clinical Epidemiology 50(12):
       1311-1318.
       ReplyDelete
    4. [anon36.png]
       Anonymous7:58 AM
       Stephen, thanks for your reply and the links. I agree with your
       point about pragmatism but I also see the value of a carefully
       controlled assessment of efficacy & harms - not least to avoid Type
       I error for the former and Type II for the latter. I think there
       must be room for both approaches...
       P.s are you the Stephen Senn of CROS analysis fame?
       Paul
       ReplyDelete
    5. [anon36.png]
       Paul Ivsin12:00 PM
       I also am failing to fully grasp the ethical problems of this study
       design, and of attempting to reduce the placebo response in RCTs in
       general. Presumably, reductions in placebo response would happen
       across all arms of the trial equally, which would provide a clearer
       picture of the specific chemical activity of the drug.
       The major problem with the design seems to be -- as Stephen points
       out in the first comment -- that it probably won't reduce the total
       placebo effect size much. If placebo responders were likely to
       remain consistent in their response, then we'd already have a
       simple solution in the placebo run-in period. The problem being, of
       course, that there's really no evidence that run-in periods do what
       they're supposed to do.
       I actually wrote a brief blog post about the SPCD a couple years
       ago (here). Then, I asked essentially the same question as now:
       what evidence to we have that SPCD reduces placebo response
       compared to more traditional methods?
       (and a second question for the author: if SPCD is an unethical
       design, then wouldn't a design featuring a placebo run-in -- which
       most trials use -- also be unethical?)
       ReplyDelete
    6. [anon36.png]
       Anonymous12:52 PM
       The problem is that there are some people in both treatment and
       control groups who are placebo-responders -- they will respond no
       matter what you give them. Responders therefore have to be kept in
       the control group as the proper baseline for comparison. If they're
       left out in any way, you're comparing apples and oranges -- a
       treatment group that includes some unknown placebo responders
       (whose response to the drug is therefore inflated) is being
       compared to a control group that excludes placebo responders.
       Right?
       ReplyDelete
    7. [anon36.png]
       Jim10:32 PM
       I think the issues here are a little more complicated than
       presented by the author.
       We have a simple observation, that drugs that robustly separated
       from placebo 20 years ago no longer reliably do so. Did they become
       less active? Probably not. Are placebos working better than they
       used to? Probably, at least within the clinical trial setting.
       Assuming that is the case, what should we do?
       1)We could remove all these drugs from the market, and simply give
       patients placebos. But its not really clear whether the placebo
       effect would continue to operate once word got out that doctors
       were routinely handing out placebo. In fact once study found that
       the magnitude of the placebo effect is proportional to the
       likelihood of receiving active drug.
       2)We could leave the old drugs on the market and not approve the
       new ones. However the new drugs appear to be equally efficacious to
       the old ones, and in many cases (e.g., lurasidone) have better side
       effect profiles. This would seem not to serve the interests of
       patients either.
       3)We could attempt to make clinical trials look more like real life
       treatment, in which the choices are not between drug and placebo
       but between drug and no treatment. But this would lead to drugs
       with no intrinsic efficacy being approved as a matter of course.
       4)We can try to understand the placebo effect, and engineer it out
       of trials so that we know that approved drugs have greater efficacy
       that placebo under at least some test conditions.
       I would say that choice #4 is probably the best of those that I can
       come up with. For all the insinuations in the article about how
       pharma is trying to pull the wool over everyone's eyes, it seems
       that given the available choices, the industry is pursuing the only
       one that really makes any sense.
       Obviously we would all like to have more efficacious drugs whose
       effects are so robust that the issue of establishing separation
       from placebo never arises. If the author has any ideas on how such
       compounds might be produced, I'm sure there are venture capitalists
       who would be strongly interested to hear them.
       ReplyDelete
    8. [anon36.png]
       Anonymous7:40 AM
       Jim, very interesting points.
       Something that doesn't seem to be getting enough consideration from
       the industry is that improvements in trial methodology (governance,
       oversight, pre-registration, CONSORT etc) has reduced risk of bias,
       both in relation to trial conduct and reporting, and that this
       might account for some of the increased placebo effect. I wonder
       what your view on this is?
       If I am right, then it follows that older trials overestimated
       efficacy.
       Paul
       ReplyDelete
    9. [anon36.png]
       Anonymous7:39 AM
       to Jim: you are assuming that the only option is to treat patients
       with drugs(be it placebo or "real" effective drugs). However, at
       least in case of depression, psychotherapy can be highly effective:
       take cognitive behavioural therapy as good example. There are even
       options for self-therapy(look at the excellent book by CBT
       therapist David Burns "Feeling Good: the new mood therapy").
       So no, the industry isn't "pursuing the only one that really makes
       any sense."
       ReplyDelete
   10. [anon36.png]
       Anonymous9:39 AM
       I remember having read a very enlightening piece about why the old
       drugs don't work these days: they never did, and the reason is
       really simple: the industry would only publish studies that showed
       a positive effect and hide those that showed a negative effect. Bad
       study design and reporting bias does the rest.
       You always get studies with a positive outcome, even if the drug
       itself does not work.
       So any study design that tries to lower placebo response is a great
       idea for the industry, because that is a cost-effective way of
       creating more studies with positive outcome, independently of the
       efficay of the drug.
       Now tell me, what's not to love about that?
       Bernard
       ReplyDelete
   11. [anon36.png]
       mendelid11:22 AM
       Statistically, I can see arguments both ways.
       Pro SPCD:
       If we assume that a psychiatric diagnosis describes a symptom
       rather than an underlying cause, and that placebo is efficient at
       counteracting one cause and the medication efficient at
       counteracting another, and both are equally strong and independent
       of each other, then we would get the same number of positive
       responses for each medication, yet it would still make sense to
       have that medication. The SPCD would in this case show that the
       medication is efficient for causes where the placebo isn't. An
       ineffective medication that only works through the placebo effect
       should still fail SPCD studies. (An additional argument pro SPCD is
       that due to the low efficacy of psychiatric drugs, practitioners
       test patients on one drug, and if it doesn't work, switch them to
       another one. SPCD mimics this practice by switching patients on
       whom the placebo didn't work to the medication being tested. Thus
       it could be said to be more relevant to actual medical practice.)
       Contra SPCD:
       The above argument assumes that the placebo effect works the same,
       no matter if it's the medication or the actual placebo that causes
       it. However, that may not be true. In that case, the SPCD may
       simply funnel a higher percentage of subjects into the second phase
       who are able to detect placebos (e.g. through missing side
       effects). For these people, the placebo effect of the real drug may
       be stronger, perhaps because they're noticing side effects that
       weren't present in the previous placebo trial, so they (correctly)
       conclude they're now given "the real thing", making the placebo
       effect work for them.
       ReplyDelete
   12. [anon36.png]
       Anonymous11:09 AM
       Didn't you jump the gun with this article, by about a week?
       "The drug companies say these failures are happening not because
       their drugs are ineffective, but because placebos have recently
       become more effective in clinical trials."
       Hahahaa!!! But wait, the date says March 24!
       ReplyDelete
   13. [anon36.png]
       greentess1:09 PM
       Thank you for sharing. The ViS platform enables clinical research
       optimization.
       ReplyDelete
   14. [anon36.png]
       Earn Money Clinical Trials8:26 PM
       Why it has to be reduced if it is getting to its way in being
       effective at all?
       ReplyDelete

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   Research Article

Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue
Conditioning and Their Association

     * Jian Kong mail,
       * E-mail: kongj@nmr.mgh.harvard.edu
       Affiliation: Psychiatry Department, Massachusetts General Hospital
       and Harvard Medical School, Charlestown, Massachusetts, United
       States of America
       X
     * Rosa Spaeth,
       Affiliation: Psychiatry Department, Massachusetts General Hospital
       and Harvard Medical School, Charlestown, Massachusetts, United
       States of America
       X
     * Amanda Cook,
       Affiliation: Psychiatry Department, Massachusetts General Hospital
       and Harvard Medical School, Charlestown, Massachusetts, United
       States of America
       X
     * Irving Kirsch,
       Affiliations: Program in Placebo Studies, Beth Israel Deaconess
       Medical Center, Harvard Medical School, Boston, Massachusetts,
       United States of America, School of Psychology, Plymouth
       University, Plymouth, United Kingdom
       X
     * Brian Claggett,
       Affiliations: Division of Cardiovascular Medicine, Harvard Medical
       School, Boston, Massachusetts, United States of America,
       Biostatistics Department, Harvard School of Public Health, Boston,
       Massachusetts, United States of America
       X
     * Mark Vangel,
       Affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for
       Biomedical Imaging, Charlestown, Massachusetts, United States of
       America
       X
     * Randy L. Gollub,
       Affiliation: Psychiatry Department, Massachusetts General Hospital
       and Harvard Medical School, Charlestown, Massachusetts, United
       States of America
       X
     * Jordan W. Smoller,
       Affiliation: Psychiatry Department, Massachusetts General Hospital
       and Harvard Medical School, Charlestown, Massachusetts, United
       States of America
       X
     * Ted J. Kaptchuk
       Affiliation: Program in Placebo Studies, Beth Israel Deaconess
       Medical Center, Harvard Medical School, Boston, Massachusetts,
       United States of America
       X

     * Published: July 31, 2013
     * DOI: 10.1371/journal.pone.0067485

     * Article
     * About the Authors
     * Metrics
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Abstract

   Placebo treatments and healing rituals have been used to treat pain
   throughout history. The present within-subject crossover study examines
   the variability in individual responses to placebo treatment with
   verbal suggestion and visual cue conditioning by investigating whether
   responses to different types of placebo treatment, as well as
   conditioning responses, correlate with one another. Secondarily, this
   study also examines whether responses to sham acupuncture correlate
   with responses to genuine acupuncture. Healthy subjects were recruited
   to participate in two sequential experiments. Experiment one is a
   five-session crossover study. In each session, subjects received one of
   four treatments: placebo pills (described as Tylenol), sham
   acupuncture, genuine acupuncture, or no treatment rest control
   condition. Before and after each treatment, paired with a verbal
   suggestion of positive effect, each subject's pain threshold, pain
   tolerance, and pain ratings to calibrated heat pain were measured. At
   least 14 days after completing experiment one, all subjects were
   invited to participate in experiment two, during which their analgesic
   responses to conditioned visual cues were tested. Forty-eight healthy
   subjects completed experiment one, and 45 completed experiment two. The
   results showed significantly different effects of genuine acupuncture,
   placebo pill and rest control on pain threshold. There was no
   significant association between placebo pills, sham acupuncture and cue
   conditioning effects, indicating that individuals may respond to unique
   healing rituals in different ways. This outcome suggests that placebo
   response may be a complex behavioral phenomenon that has properties
   that comprise a state, rather than a trait characteristic. This could
   explain the difficulty of detecting a signature for “placebo
   responders.” However, a significant association was found between the
   genuine and sham acupuncture treatments, implying that the non-specific
   effects of acupuncture may contribute to the analgesic effect observed
   in genuine acupuncture analgesia.

   Citation: Kong J, Spaeth R, Cook A, Kirsch I, Claggett B, et al. (2013)
   Are All Placebo Effects Equal? Placebo Pills, Sham Acupuncture, Cue
   Conditioning and Their Association. PLoS ONE 8(7): e67485.
   doi:10.1371/journal.pone.0067485

   Editor: Sam Eldabe, The James Cook University Hospital, United Kingdom

   Received: February 17, 2013; Accepted: May 18, 2013; Published: July
   31, 2013

   Copyright: © 2013 Kong et al. This is an open-access article
   distributed under the terms of the Creative Commons Attribution
   License, which permits unrestricted use, distribution, and reproduction
   in any medium, provided the original author and source are credited.

   Funding: This work was supported by KO1AT003883 (NCCAM), R21AT004497
   (NCCAM), R03AT218317 (NIDA), and R01AT006364 (NCCAM) to Jian Kong;
   R01AT005280 (NCCAM) to Randy Gollub; K24AT004095 (NCCAM) to Ted
   Kaptchuk; K24MH094614 (NIMH) to Jordan W. Smoller, and P01 AT006663
   (NCCAM) to Bruce Rosen. The funders had no role in study design, data
   collection and analysis, decision to publish, or preparation of the
   manuscript.

   Competing interests: The authors have declared that no competing
   interests exist.

Introduction

   Placebo treatments and healing rituals have been used since the
   beginning of human history [1], [2]. The systematic study of placebo
   and ritual is still in its infancy [3], [4]. Whether all placebo
   treatments, or medical rituals, have equivalent effects remains
   unknown. This raises the question: Do patients who respond to one
   placebo intervention also tend to respond to other placebo
   interventions?

   In a previous clinical trial [5] of chronic pain patients, we found
   that sham acupuncture reduced pain significantly more over time than
   did placebo pills, while placebo pills offered more short-term benefits
   of improving pain-disturbed sleep over sham acupuncture. Thus it showed
   that not all placebo treatments are equal. However, this clinical trial
   involved multiple, concurrent experimental arms and was not designed to
   answer the question of whether individuals who tend to respond to sham
   acupuncture also tend to respond to placebo pills.

   In another study [6], Colloca and colleagues compared the placebo
   effects of verbal suggestion and conditioning to a control condition
   and found that verbal suggestion alone could not produce significant
   differences in subjective pain ratings. Conditioning, on the other
   hand, could significantly reduce subjective pain ratings. The
   between-subject design of this study prevents the authors from
   elucidating the association between verbal suggestion and conditioning
   effects.

   Elucidating the relationship between different placebo modalities
   paired with verbal suggestion (suggestion-evoked placebo effects) as
   well as understanding their association with conditioning-evoked
   placebo effects will enhance our understanding of the variability
   observed in the placebo response. We are particularly interested in
   whether placebo responses can be characterized by the involvement of
   relatively stable traits or states, depending on particular
   circumstances.

   Acupuncture has been used to relieve pain in East Asia for two thousand
   years [7]. Recent clinical trials investigating acupuncture's effects
   on chronic pain have shown contradictory results and often fail to show
   superiority over sham acupuncture [8]. This ambiguity may be the result
   of acupuncture's sizeable placebo effects as well as large
   inter-individual variability in response to acupuncture treatment [5],
   [8]–[11]. It is well known that some patients respond well to placebo
   and acupuncture treatments while others do not [5], [9]. Thus, as a
   secondary aim, this paper also addresses whether individuals who
   respond to sham acupuncture also respond to genuine acupuncture.

   In this study, all subjects participated in two experiments
   sequentially. The first experiment was a multi-session crossover study
   [12] designed to test the analgesic effects of placebo Tylenol (pill),
   sham acupuncture, and genuine acupuncture (electroacupuncture) as
   compared to a no treatment (rest control). Subjects also participated
   in experiment two, in which we investigated how visual cues could
   modulate pain perception. These two experiments allow us to investigate
   the relationship between the analgesia evoked by different treatments
   as well as the analgesic effect evoked by conditioning cues.

Methods

Experiment one

Subjects.

   Seventy-one healthy, acupuncture-naïve subjects were recruited from the
   community, using flyers and postings, and enrolled in the study. The
   Institutional Review Board at Massachusetts General Hospital approved
   the study and all subjects gave written informed consent before
   commencing experiment one. All subjects were told that if they
   completed experiment one, they would also be invited to participate in
   experiment two. Subjects were debriefed at the end of experiment two
   and investigators explained the rationale for deception during the
   experiments. All subjects found study procedures acceptable and agreed
   to have their data used for analysis.

Outcome measurements.

   The outcome measures for this study include heat pain threshold and
   tolerance and subjective pain ratings of calibrated heat pain. All pain
   assessments were appliedusing a TSA-2001 Thermal Sensory Analyzer with
   a 3×3 cm probe (Medoc Advanced Medical Systems, RimatYishai, Israel)
   running proprietary computerized visual analog scale software (COVAS).

   Subjects' thresholds and tolerances to pain were assessed on the dorsal
   portion of the hand using an ascending method of limits paradigm with a
   rate of rise of 0.5°C/sec from a baseline of 32°C. The 3 cm X 3 cm
   thermode was held lightly in place on the skin by a member of the study
   staff blinded to treatment mode.Subjects pressed a button in front of
   them to indicate when the heat “first becomes painful”to indicate pain
   threshold and when the heat “becomes too painful to tolerate” to
   indicate tolerance. Three trials of pain threshold and tolerance
   assessments were performed. The thermode was repositioned between each
   trial.

   Calibrated heat pain stimuli were applied on the volar side of the
   forearms. All stimuli were delivered in 10-secondsegments (including an
   approximate 2.5 second ramp up and down from baseline) with a minimum
   inter-stimulus interval of 24 seconds. After each stimulus, the
   subjects were asked to rate the pain using the Gracely Sensory Scale
   (0–20) [13], [14].

Experimental procedure.

   The first experiment was a crossover study that involved five study
   visits, including one training session and4experimental sessions
   (Figure 1). Each session was separated by at least 3 days to avoid
   sensitization to the repeated application of the noxious stimuli and to
   allow for full recovery of the subjects' skin. Similar methods have
   been used in our previous studies and no damage or lesions have been
   observed [12], [15]–[17].
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   Figure 1. Experimental design.
   doi:10.1371/journal.pone.0067485.g001

   The first session was used to introduce the study procedures, determine
   appropriate stimulus intensities for each subject, minimize
   anticipatory anxiety to pain and acupuncture, and to control for rating
   strategy and learning effects.

   At the beginning of the training session (Session 1),subjects were told
   that in the subsequent 4 sessions, they would receive each of the 4
   experimental conditions in a randomized order, i.e. two different modes
   of acupuncture treatment(electroacupuncture and manual acupuncture),
   one painkiller (Tylenol), and one control condition. Subjects were also
   told that before and after each treatment condition and the control
   condition, trained study staff would test their pain sensations to
   investigate the analgesic effect of different treatments on
   experimental pain applied to the forearm.

   In reality, the manual acupuncture was sham acupuncture and the Tylenol
   painkiller was a placebo pill. In addition, subjects were explicitly
   informed that the control condition was a baseline control for the
   study and, thus, no treatment effects were expected. To maintain
   uniform expectancy across treatment sessions, subjects were also told
   that the effects of the two types of acupuncture (electroacupuncture
   and manual acupuncture) and Tylenol treatments could work via different
   mechanisms, and that the efficacy of one treatment would not influence
   the efficacy of the others.

   The subjects were then trained to assess their pain threshold and
   tolerance. The heat stimuli were applied to the back of their hand in
   three separate locations for both threshold and tolerance measures.
   After that, they were instructed how to use the Gracely Sensory and
   Affective Scales [13], to rate calibrated heat pain with methods used
   in our previous studies [12], [15]–[17]. In order to identify the
   individually calibrated heat pain stimuli, a training set of ascending
   heat pain stimuli was administered starting from 38°C and increasing by
   one degree for each stimulus. From the subject's ratings of this
   initial series of stimuli, two heat pain intensities were determined
   for each subject: one to elicit responses in the strong range (“High
   pain”; 14–17 on the Sensory Scale) and one to elicit responses in the
   mild to moderate range (“Low pain”; 8–11 on the Sensory Scale).
   Sequences of the subject-specific High and Low stimuli were then
   applied in random order to separate areas of skin on the right volar
   forearm to further test the reliability of these ratings. Each random
   sequence consisted of six stimuli:3 Low pain stimuli and 3 High pain
   stimuli. The high and low temperatures were adjusted as necessary to
   reliably elicit a High or Low rating from a subject. Following these
   adjustments, the temperatures would remain fixed for all subsequent
   sessions.

   Next, acupuncture was administered for 2 minutes to introduce subjects
   to the acupuncture experience. As several previous studies [18]–[20]
   have suggested that optimism is associated with placebo effects, all
   subjects were asked to complete the Life Orientation Test (LOT) to
   assess individual differences in generalized optimism versus pessimism.

   Study sessions 2–5 were experimental test sessions. In each
   experimental session, a predetermined set of experimental heat pain
   tests was administered before and after treatment/conditioning in the
   following order: 1) pain threshold (3 times) on the dorsal portion of
   the right hand; 2) a pseudorandom noxious thermal stimuli sequence
   consisting of the 3 High and 3 Low pain stimuli on the volar side of
   right forearm; and 3) heat pain tolerance on the dorsal portion of the
   right hand. The dorsal portion of the hand was chosen due to its
   proximity to the acupuncture point used in this study. Heat pain was
   applied to separate areas of skin on the volar forearm in order to
   avoid the potential influence of one sequence of calibrated pain on
   each subsequent sequence. This predetermined set of tests was repeated
   during each experimental session. The only difference among the
   sessions was the treatment condition: electroacupuncture, sham
   acupuncture, placebo Tylenol, or rest control condition. The order in
   which subjects received the 4 experimental conditions was randomized
   prior to study proceedings using a computerized random number
   generator. Sequentially numbered method was applied for allocation
   concealment.

   To ensure that all subjects could consistently rate the discrete levels
   of heat pain, only subjects who demonstrated the ability to distinguish
   different pain intensities during Session 2 (i.e., on average, rating
   the High pain stimuli higher than the Low pain stimuli after
   application of the random noxious stimuli sequence) were selected to
   proceed in the study.

   Studies have shown that expectation can significantly influence an
   individual's perception of pain [15]–[17],[21]–[28]. Thus, all subjects
   were asked to complete the Expectations for Relief Scale (ERS) to
   indicate how much pain relief they expected from each particular
   treatment after receiving the treatment but prior to the post-treatment
   pain testing. The ERS is a ten-point scale (0–10) where 0 indicates a
   very negative expectation of “does not work at all” and 10 indicates a
   very positive expectation of “complete pain relief.”For the three
   treatment conditions, the subjects were told prior to treatment that
   they were about to receive a treatment that the investigators believed
   would have an analgesic effect on their entire body, including the arm.
   This served as verbal suggestion for the subjects in the treatment
   groups. For the control condition (30-minute rest period), subjects
   were still required to use ERS to rate how they expected their pain
   sensitivity would change after a 30-minute break, although they
   received no treatment.

Interventions.

   Placebo Tylenol Pill: Subjects were informed that the goal of the
   session was to test the analgesic effect of a non-opioid analgesia
   pill, acetaminophen (Tylenol by brand), on experimental pain. They were
   also told that the pill would begin to take effect approximately half
   an hour after administration and that previous research has suggested
   that Tylenol can produce a general analgesic effect on the whole body,
   including the experimental pain applied to the forearms. After orally
   ingesting the pill (in reality an inert placebo pill), subjects waited
   about half an hour prior to the beginning of the post-treatment pain
   assessment.

   Sham (Placebo) Acupuncture: Sham acupuncture was performed using the
   validated Streitberger sham acupuncture device [12], . A small plastic
   ring was covered by an opaque, thin covering and then placed
   over2non-acupoints after the acupuncturist disinfected the area with
   isopropyl alcohol. A placebo needle, which was visually
   indistinguishable from genuine acupuncture needles, was inserted into
   the center of the ring and held in place by the tape. Because the
   Streitberger placebo needle has a blunt tip and a retractable shaft,
   the needle did not actually penetrate the skin; however the subjects
   felt a sensation similar to that of a pinprick or a scratch. After
   insertion, the needles were kept in place for 25 minutes.

   Two sham acupoints (sham large Intestine 4 and 3 (LI 4 and LI 3) were
   chosen [32].Sham acupoint LI 4 is located on the dorsum of the right
   hand, between the 1st and 2nd metacarpal bones, approximately in the
   middle of the 1st metacarpal bone on the ulnar side. Sham acupoint LI 3
   is about one half cm above the metacarpal bones. Both needles were
   rotated until the subject reported some level of sensation. Then, all
   needles were left alone for the remainder of the procedure (about 23
   minutes) without further manipulation. The subject was told that these
   proceedings constituted the manual acupuncture treatment.

   Genuine Acupuncture: The acupoints LI 4 and LI 3 on the right hand were
   used for the genuine acupuncture treatment. These points have
   well-documented analgesic effects in laboratory experiments [12], [33],
   [34]. After the acupuncturist located the acupoint and disinfected it
   with isopropyl alcohol, a small plastic ring was placed over the
   acupoint and secured with a thin strip of sterile plastic tape. This
   covering was used to maintain subject blinding to genuine and sham
   acupuncture conditions.

   A small alligator-type conducting clamp was then attached to each
   needle to create a circuit using an electroacupuncture device (OMS
   Medical Supplies IC-1107). A current was passed through the electrode
   at a continuous frequency of 2 Hz. The intensity of the stimulation was
   gradually increased to the highest level subjects could tolerate
   without the sensation of sharp pain. The electroacupuncture was applied
   for approximately 23 minutes. Immediately following each acupuncture
   treatment (genuine and sham acupuncture treatment), subjects quantified
   the sensations they felt around the stimulated acupoint using the MGH
   Acupuncture Sensation Scale (MASS) [12], [35].

   No treatment rest control: The subjects in this group were told that
   the no-treatment condition was used as a within-subject control for the
   treatment conditions. Following the initial pain assessments, subjects
   were told to simply sit and relax for 30 minutes and wait for the
   post-treatment pain assessment to begin. Again, the subjects were asked
   to rate how much they thought the half hour rest period would change
   their sensitivity to pain during the second set of pain assessments.

Experiment two

   All subjects who completed experiment one were invited to return to our
   lab at least 2 weeks after completion of experiment one to participate
   a one-session fMRI study to investigate the conditioning effects of
   visual cues. Please see original publication for more details on
   experimental procedures and fMRI results [36]. The present manuscript
   only focuses on the analysis of the association between the placebo
   effects evoked by suggestion in experiment one and the visual cue
   conditioning effects in experiment two. This analysis has not been
   included in previous reports.

   In brief, at the beginning of the experiment, subjects were told that
   the aim of experiment two was to investigate the brain's response to
   different levels of thermal pain. Subjects were then familiarized with
   the visual presentation paradigm, including a pre-stimulus cue, a pain
   stimulus symbol, and a post-stimulus rating scale. In addition,
   subjects were told that the pre-stimulus cue (text saying either “HIGH”
   or “LOW”) would indicate the level of the subsequent pain stimulus.

   Based on experiment one, temperatures that elicited subjective
   intensity ratings in the strong range (“High pain”; 14–17 on the
   Sensory Scale) and one to elicit responses in the mild to moderate
   range (“Low pain”;8–11 on the Sensory Scale)were selected for each
   subject and used in experiment 2 (MRI study). Immediately prior to the
   fMRI scan, a brief pain sensitivity test was performed to further
   confirm that the subjective ratings in response to the high and low
   temperature stimuli elicited were within the targeted range for the
   study and necessary adjustments were made.

   During fMRI scanning, 3 different series of pseudo-randomized pain
   sequences were applied to the distal portion of the right forearm above
   the wrist. Subjects were instructed to focus on a small black fixation
   cross in the center of the screen in front of them. The first scan was
   a contextual conditioning/learning scan where subjects were presented
   with a pre-stimulus cue, indicating (without deception) whether they
   would be administered a LOW or HIGH pain stimulus. The duration of the
   pain stimulus was 12 seconds and the intensity of the stimulus for this
   first sequence always corresponded to the pre-stimulus cue. After each
   pain stimulus, the Sensory Box Scale was displayed on the screen for 8
   seconds, and subjects rated the intensity of their subjective pain by
   moving a cursor along the scale. In total, this learning sequence
   included 4 LOW and 4 HIGH pain stimuli.

   The initial conditioning scan was followed by 2 test pain sequences in
   which the LOW cue (LC) was sometimes followed by the HIGH pain stimulus
   (HP) (the LC condition), representing a condition where subjects were
   expected to report less pain in response to a suggested low stimulus,
   and sometimes followed by the LOW pain stimulus. Both test scans
   included nine stimuli, where 3 of the stimuli were cued as HIGH pain
   and six were cued as LOW pain. Following all HIGH cues (HC), a high
   pain stimulus was delivered (the HC condition). However, following 3 of
   the six LOW cues, a HIGH pain stimulus was delivered (the LC condition)
   instead of a LOW pain stimulus. All other timing aspects of the 2 test
   scans were identical to the first contextual learning/conditioning
   scan. The subjective pain ratings evoked by the different cues (LC or
   HC with identical HIGH heat pain stimuli) in runs 2 and 3 were used to
   calculate the conditioned cue effect. The cue effect was used to
   investigate the association between the analgesic effect of treatment
   observed in experiment one and the analgesic effect of visual cue
   conditioning.

Analysis

Experiment one

   The primary outcomes for experiment one were post-treatment measures of
   pain threshold, pain tolerance, and pain ratings (for high pain and low
   pain). Because each subject was evaluated under all 4 of the
   experimental conditions, the data were analyzed using repeated measures
   analysis of covariance (ANCOVA) with the corresponding baseline
   measures as the covariate and treatment as the factor of interest. A
   separate ANCOVA model was fit for each of the 3outcomes. In these
   ANCOVA models, session order and subject ID were also included as
   factors, eliminating the need to further control for subject-level
   covariates such as age and gender.

   For each subject outcome, the distribution of residuals from the ANCOVA
   model was visually inspected. In the event that noticeable
   non-normality was detected, a robust analysis rank ANCOVA was
   performed, replacing both outcomes and baseline scores with their
   respective ranked values [37]. If both normal-theory and robust
   analyses produced similar results, we concluded that the results were
   not likely to be sensitive to the normality assumption.

   For outcomes in which a significant difference among treatments was
   detected, regression analyses were used to investigate whether
   subject-level outcomes (including subject response to other treatments)
   were useful predictors of response to genuine acupuncture. Robust
   regression using M-estimation was employed to minimize the effect of
   outliers [38].All analyses were conducted using Stata (version 11).
   P-values of ≤0.05 were considered to be statistically significant.

Experiment two

   The primary outcome for experiment two was the subjective pain ratings
   evoked by the different visual cues (Low Cue or High Cue with identical
   HIGH heat pain stimuli) in the 2 test pain sequences. We explored the
   association between the analgesic effect evoked by different treatments
   in experiment one (genuine acupuncture, sham acupuncture and placebo
   pills compared with rest condition, separately) and visual cue effects
   in experiment two by applying non-parametric Spearman correlations
   separately. For this analysis, we used the primary outcomes of
   experiment one (changes in pain threshold, pain ratings of calibrated
   pain stimuli and pain tolerance), and the primary outcome in experiment
   two (conditioning cue effects as indicated by subjective pain rating
   changes to identical pain stimuli).

Results

Experiment one

   Of the 71 healthy subjects who participated the study, 48 subjects (19
   males, 34 white, 4 black, 6 Asian, 3 more than one race and 1 unknown)
   ages 21–37 (mean: 26.23, SE: 0.48) completed experiment one with data
   for analysis. One subject who completed experiment one was not included
   in data analysis due to missing data. Twenty-two subjects did not
   complete the study. The reasons for dropped subjects included
   scheduling difficulties (11), unstable pain ratings (6), inability to
   tolerate testing conditions (acupuncture or heat) (3), inability to
   understand nuances of pain rating scales (1), and voluntary withdrawal
   (1). The average intervals between treatments (baseline and each of the
   four conditions) were 8 days, 7.7 days, 7.5 days and 8.2 days.

   A summary of pain threshold and tolerance values and pain ratings of
   calibrated heat pain stimuli are shown in Table 1 and Figure 2. The
   ANCOVA (Table 2) showed that pain threshold post-treatment scores were
   significantly dependent on the mode of treatment (F = 3.57; df = 3,
   137; p = 0.016). The distribution of the post-treatment scores, as well
   as the residual values from the ANCOVA model, was found to include
   outliers, which could potentially impact the results of the ANCOVA
   model. However, the sensitivity analysis conducted using rank data
   found a similar result (F = 3.63; df = 3, 137; p = 0.015). Post hoc
   analysis among the 4 experimental conditions showed that both genuine
   acupuncture and placebo pills produced significant post-treatment pain
   threshold increases (+0.79, 95% CI:[+0.25, +1.33], p = 0.004; and
   +0.74,95%CI: [+0.19, +0.1.29], p = 0.008 respectively) relative to rest
   control. No other significant differences between treatments were
   detected with respect to pain threshold (Table 3).
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   Figure 2. Summary of pain measurement difference (post- minus
   pre-treatment, mean ± SE) on pain threshold, pain tolerance, and pain
   rating across different groups.

   EA, electroacupuncture group; PA, placebo acupuncture group; PT,
   placebo Tylenol group; RS, resting control group.
   doi:10.1371/journal.pone.0067485.g002
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   Table 1. Pre- and post-treatment pain threshold (centigrade), tolerance
   (centigrade), and pain ratings (intensity rating of high and low pain
   stimuli using the 0–20 GracelyScale) across different conditions
   (mean±SE).
   doi:10.1371/journal.pone.0067485.t001
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   Table 2. Treatment effects across different measurements of pain
   sensation.
   doi:10.1371/journal.pone.0067485.t002
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   Table 3. Post-hoc analysis of pain threshold: effect of treatment
   relative to rest control.
   doi:10.1371/journal.pone.0067485.t003

   For pain ratings of calibrated heat pain stimulation and pain
   tolerance, no significant treatment effects were detected (Table 2).
   While the null hypothesis of global F-test for the effect of treatment
   on the pain tolerance outcome could not be rejected, it should be noted
   that an exploratory post-hoc analysis using a test for detecting trends
   across the treatment groups did reveal a significant progression in the
   strength of treatment effects when the treatments were ordered as rest
   control condition<placebo Tylenol = sham acupuncture
   <electroacupuncture. In this analysis, the effect of treatment was
   estimated, with the rest condition coded as 0, each of the two placebo
   treatments coded as 1, and the genuine acupuncture coded as 2. Using
   the same ANCOVA models as mentioned above, the effects of treatment
   were found to be significant with p-values of 0.012 and 0.007
   corresponding to the original and ranked data, respectively.

   Because only the pain threshold outcome showed significant differences
   among the experimental conditions, further analyses focused only on
   this outcome. In an attempt to determine whether responses to placebo
   Tylenol were significantly related to each subject's response to sham
   acupuncture, we investigated the relationship between post-treatment
   placebo Tylenol pain threshold and the following predictors,
   controlling for pre-treatment placebo Tylenol pain threshold: pre- and
   post-sham acupuncture pain threshold change, pre- and
   post-electroacupuncture pain threshold change, pre- and post- rest
   control pain threshold change, expectancy ratings for each of the4
   conditions(placebo Tylenol, sham acupuncture, genuine acupuncture, and
   rest control), age, gender, and optimism measured by the LOT scale.

   We assessed these relationships via univariate and multivariate
   regression models. The results (Table 4) show the estimated regression
   coefficients and associated p-values. In the left column, each variable
   is considered one at a time, controlling only for baseline placebo
   Tylenol pain threshold and the session number in which placebo Tylenol
   was received. In the right column, all variables appear together in a
   single multivariate model. In both settings, there is no significant
   association between post-treatment placebo Tylenol pain threshold and
   the sham acupuncture pain threshold change, suggesting the 2 placebo
   modalities are not associated. No other predictors were found to be
   significantly related to placebo Tylenol pain threshold in either
   univariate or multivariate models.
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   Table 4. Potential predictors of placebo Tylenol response using pain
   threshold as outcome.
   doi:10.1371/journal.pone.0067485.t004

   Similarly, in an attempt to determine whether any individual
   characteristics were significantly related to subject response to
   electroacupuncture, we investigated the relationship between
   post-treatment electroacupuncture pain threshold and the following
   predictors, controlling for pre-treatment electroacupuncture pain
   threshold as well as the session number in which electroacupuncture was
   received: pre- and post- sham acupuncture pain threshold change, pre-
   and post-placebo Tylenol pain threshold change, pre- and post- rest
   control pain threshold change, expectancy ratings for each of the 4
   conditions(genuine acupuncture, sham acupuncture, placebo Tylenol, and
   rest control), age, gender, and optimism measures using the LOT scale.

   The results (Table 5) show the estimated regression coefficients and
   associated p-values. In both settings, the sham acupuncture pain
   threshold change was significantly and positively correlated to post-
   electroacupuncture pain threshold (β = 0.41, p = 0.005 in univariate
   model; β = 0.41, p = 0.03 in multivariate model).
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   Table 5. Potential predictors of electro-acupuncture response using
   pain threshold as outcome.
   doi:10.1371/journal.pone.0067485.t005

   After each treatment, the expectancy for that particular treatment was
   also measured using the ERS. The average expectancy ratings (avg ± SE)
   for each of the 4 experimental conditions are: 4.4±0.3 for the genuine
   acupuncture condition, 4.1±0.4 for the sham acupuncture condition,
   5.3±0.3 for the placebo Tylenol condition, and 0.6±0.2 for the rest
   control condition. The ANOVA showed that there was a significant
   difference in expectancy ratings across the 4 experimental conditions
   (F(3,137) = 79.6, p<0.0001), and post hoc analysis showed that
   expectancy rating in all 3 treatment groups were significantly greater
   than the rest control condition (p<0.001 for each). Expectancy ratings
   in the placebo Tylenol condition were also greater than both the sham
   acupuncture condition (p = 0.001) and the genuine acupuncture condition
   (p = 0.003).

   To further test the association between the pre- and post-treatment
   pain measurement differences and expectancy ratings, we regressed all
   post-treatment pain measurements on expectancy scores, controlling for
   pre-treatment measurements, session order, and subject ID. The results
   indicated that the expectancy level was significantly correlated with
   pain threshold (beta = 0.17, p<0.001) and pain tolerance (beta = 0.07,
   p = 0.003), but not significantly associated with low and high pain
   ratings.

   We also measured the sensations evoked by electro-acupuncture and sham
   acupuncture treatment using the MASS. A summary of the results is shown
   in Table 6. There was a significant difference in the average MASS
   sensation between electro-acupuncture (2.2±1.5) and sham acupuncture
   (0.5 ±0.6) conditions (p<0.001). Correlation analysis did not find
   significant correlations between the MASS rating and outcome
   measurements (pain threshold, pain tolerance and pain rating changes).
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   Table 6. Average MASS scores (mean ± SE) across electro-acupuncture and
   sham acupuncture conditions.
   doi:10.1371/journal.pone.0067485.t006

Experiment two

   Of the 48 datasets that were included in analyses from experiment one,
   data from 46 subjects were included in data analysis for experiment
   two. One subject was not able to complete experiment due to scheduling
   conflicts, and the other subject did not complete experiment two (fMRI
   scan session) due to a suspected abnormal brain scan. Subsequent follow
   up with a physician determined that the abnormality was not clinically
   significant.

   Behavioral data of experiment two showed that the pain ratings (mean±
   SE) for the low-cue low pain condition averaged 5.3±0.3, the low-cue
   high pain condition (LC) averaged 11.3±0.4, and the high-cue high pain
   condition (HC) averaged 14.2±0.3.The cue effect (LC condition minus HC
   condition) ranged from −0.5 to 7.6 (median = 3.0). A one-way mixed
   model was applied with mean pain ratings as the response, the result
   showed that the contrasts HC and LC condition was highly significant
   (p<0.0001).

   To explore the association between the analgesic effects observed from
   experiment one and the conditioning cue effects observed in experiment
   two, we applied a Spearman correlation between the analgesic effect of
   different treatments (treatment (pre-post) – control (pre-post) and cue
   effects respectively. The results showed that that there was no
   association between the conditioning cue effect and any
   treatment-evoked analgesic effect (p-values ranged from 0.13–0.99).

Discussion

   In this study, we investigated the analgesic effects produced by
   placebo Tylenol, sham acupuncture, genuine acupuncture and a rest
   control condition, as well as the association between the effects of
   verbal suggestion on evoked placebo treatments (placebo Tylenol and
   sham acupuncture), electroacupuncture, and conditioning cue effects.
   The results showed that genuine acupuncture and placebo pills could
   significantly increase subjects' pain threshold compared with rest
   control condition. Regression analysis showed that there were no
   significant associations between individuals' responses to placebo
   pills, sham acupuncture, electroacupuncture and conditioning cue
   effects; however, subjects' responses to sham acupuncture correlated
   significantly with their response to genuine acupuncture.

   To the best of our knowledge, the question of whether individuals are
   likely to respond to different placebo routes of administration in a
   similar or different manner was an explicit topic of research in
   several experiments performed between 1956 and 1965 and each concluded
   that sham injections were more powerful than placebo pills
   [39]–[42].Further supporting this belief, a relatively old
   meta-analysis that included 35 RCTs for treatment of acute migraine
   extracted the placebo responses of trials that utilized an oral placebo
   and compared those responses with placebo responses in trials that used
   an injected placebo. The analysis showed that the injected placebo was
   statistically and clinically superior to the oral placebo [43].

   Our team performed an RCT comparing placebo pills and sham acupuncture
   across 270 patients with chronic arm pain. The results showed that sham
   acupuncture was statistically and clinically superior to placebo pills
   over time, while placebo pills were more beneficial in the short-term
   for improving sleep disturbances due to the pain condition [5]. A
   recent Cochrane meta-analysis of placebo effects [44] revisited this
   question of pill placebos versus device placebos and found that RCTs (n
   = 61) with “physical placebos” (which included sham acupuncture and
   such devices as sham electrotherapy and ultrasound) produced larger
   placebo effects than studies with “pharmacological” pill controls. In a
   separate study, Linde and colleagues [10] re-analyzed this
   meta-analysis [44] to investigate whether effects associated with sham
   acupuncture differed from those of other 'physical placebos'. They
   found pooled standardized mean differences were −0.41 (95% CI(−0.56,
   −0.24)) between sham acupuncture and no treatment, and −0.26 (95% CI
   −0.37, −0.15) between other physical placebos and no treatment,
   implying a larger effect of acupuncture treatment. In another
   meta-analysis from the same group [8], the authors also found that sham
   acupuncture interventions are often associated with moderately large
   nonspecific effects.

   In our present study, we did not find any differences between the sham
   acupuncture treatment and placebo pills in the measurement of pain
   threshold, tolerance, and pain ratings. Additionally, there was no
   significant association between any of the pain measurement changes
   after the 2 modes of placebo treatments (placebo pill and sham
   acupuncture) in both univariate analysis and after adjusting for
   expectancy and optimism, suggesting a lack of consistency in placebo
   response across different modes of placebo treatments. This result is
   consistent with the findings from a recent study, in which Whalley and
   colleagues [45] found that placebo effects across trials were highly
   correlated when placebo creams bore the same name but were not
   significantly correlated when placebo creams had different names.

   We did not find any significant sham acupuncture effects compared to
   the rest control. Additionally, analgesic effects across all treatment
   modes were, in general, mild. This is consistent with previous findings
   that indicate that placebo effects evoked by verbal suggestion alone
   are weak in healthy subjects compared to patients [6], [46], [47],
   particularly considering that acupuncture treatment is a novel
   treatment method in the United States [15].The fact that sham
   acupuncture had significantly lower expectancy ratings than placebo
   Tylenol further supports this view.

   Interestingly, we found that response to genuine acupuncture is
   significantly and positively correlated with response to sham
   acupuncture. This finding suggests that a non-specific effect of
   acupuncture treatment may play a significant role in the analgesic
   effect evoked by genuine acupuncture, which is consistent with the
   conclusion from a recent meta analysis on acupuncture treatment of
   chronic pain [11]. Nevertheless, our results do not indicate that the
   two are necessarily the same. We found that although the explicit
   conscious expectancy for genuine acupuncture is lower than the
   expectancy for placebo pills, the analgesic effect (as measured by pain
   threshold and tolerance) produced by genuine electroacupuncture trends
   is higher than the effect produced by placebo pills. This dissociation
   suggests that the specific effect of acupuncture may significantly
   contribute to the analgesic effect of electroacupuncture, which is
   consistent with previous neuroimaging studies that found different
   brain activation patterns associated with placebo and acupuncture
   analgesia [16], [17].

   In a previous study [6], Colloca and colleagues investigated the
   effects of both expectation, which was induced by verbal suggestion
   alone, and conditioning at the level of N1 and N2–P2 components of CO2
   laser-evoked potentials (LEPs) and subjective pain reports. They found
   that both verbal suggestions (placebo cream) and conditioning modified
   the N2–P2 complex. Verbal suggestion in combination with the
   application of placebo cream could not produce subjective pain rating
   differences as compared with control condition, while conditioning with
   placebo cream produced more robust reductions of LEP amplitudes and
   subjective pain rating decreases. Our results are consistent with their
   findings of weak placebo effects with verbal suggestion alone and
   robust effects using a conditioning paradigm. Although we cannot
   perform a direct comparison, in our results the p-value of the
   conditioned visual cue effect was more significant compared to the
   placebo effect observed with verbal suggestion alone. More importantly,
   our results extend their findings showing that there is no association
   between the placebo analgesia observed with verbal suggestion and the
   effects of visual cue conditioning, suggesting that each may be
   associated with different mechanisms.

   In this study, the most significant findings were pain threshold
   changes, but not pain tolerance or pain rating changes. Previous
   studies have suggested that different pain sensation measurements (pain
   threshold, pain tolerance, and pain rating) may represent different
   aspects of pain sensation [48], [49]. One potential explanation is the
   order effect of the pain measurements obtained. In this study, we
   collected pain threshold, then pain rating to calibrated heat pain, and
   finally the pain tolerance measurements. Since pain threshold is always
   measured first, this may partly explain why the greatest analgesia
   effect is observed in the pain threshold measurement. However, further
   study is warranted.

   Although our study is based on an experimental model in healthy
   volunteers, it may have implications for clinical care and research.
   Until now it has been understoodthat aggregate placebo responses in
   RCTs and experiments are variable [50]. Our study may suggest a new
   dimension of variability in placebo effects: responses may differ
   within individual subjects according to route of administration (pills
   vs. sham acupuncture) as well as environmental cues and learning
   processes (e.g., verbal suggestion and conditioning). This finding
   implies that placebo responses may not be dependent on stable
   individual traits but rather are more a characteristic of the state
   circumstances of individuals or combination of both trait and state.
   This result may help explain the difficulty of detecting reliable and
   consistent placebo responders [51]. Furthermore, the fact that people
   have unique responses to different routes of administration suggests
   that, for some, pills may work better than injections or vice versa.
   Moreover, the significant correlation between genuine and sham
   acupuncture on subjective outcomes suggests that elucidating whether
   acupuncture is more than a placebo effect will be difficult.

   The potential limitations of the study include the following: 1) the
   crossover design may have resulted in carryover effects and order
   effects from one study visit to the next. However, since the treatment
   sessions were separated by at least 3 days, we did not expect any
   residual effect of the previous treatment on the subsequent session.
   Additionally, each treatment session included pre-treatment
   measurements, which were used as covariates in our analysis. This
   should adjust for any residual effect from a previous treatment as well
   as other potential confounding factors, such as hyperalgesia due to
   repeated pain application; 2) The placebo effect of sham acupuncture
   was not statistically superior to no-treatment control. It is possible
   that had we had a larger placebo effect, we might have found a
   correlation between pill and sham device; 3) The study was performed on
   healthy subjects in a relatively small sample size and thus it is
   unclear whether or not similar results could be repeated in patient
   populations. These results warrant further investigation of this topic.

   In summary, in this crossover study, we found that individuals respond
   differently to different types of verbally suggested placebo treatments
   and cue conditioning. In addition, we found a significant association
   between genuine and sham acupuncture treatments, which implies that
   non-specific effects may significantly contribute to the analgesic
   effect observed in acupuncture analgesia.

Author Contributions

   Conceived and designed the experiments: JK TK IK RG JS. Performed the
   experiments: JK RS. Analyzed the data: BC IK MV AC. Wrote the paper: JK
   AC RS TK JS.

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The Mysterious Placebo

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Article

John E. Dodes

Volume 21.1, January / February 1997

   One of the most significant but widely misunderstood phenomena is the
   placebo effect. Research shows that the placebo effect can be greater
   and is far more ubiquitous than commonly thought.

     If it was so, it might be; and if it were so, it would be; but as it
     isn't, it ain't.

     -Tweedledee, in Lewis Carroll's Through the Looking Glass

   One of the questions that skeptics are asked most persistently is to
   explain how acupuncture, homeopathy, faith healing, Qigong, and other
   treatments work. Skeptics often use the placebo effect-a response to
   the act of being treated, not to the treatment itself-as an answer, but
   usually to no avail. I believe that's because most people, both logical
   and fuzzy thinkers, don't truly understand what the placebo effect is.

   Spontaneous remission and the placebo effect, which are known as
   nonspecific effects, are significant phenomena that have great impact
   on consumers and health-care professionals. Recovery from illness,
   whether it follows self-medication, legitimate treatment, or
   avant-garde therapies, may lead one to conclude that the treatment
   received was the cause of the return to good health.

   A common saying is that if you treat a cold it will last a week, but if
   you leave it alone it will be gone in seven days. Even serious diseases
   have periods of exacerbation and remission; arthritis and multiple
   sclerosis are prime examples. There are even cases of cancers
   inexplicably disappearing. The major logical error in plotting disease
   progress is: post hoc, ergo propter hoc ("after it, therefore, because
   of it"). This common fallacy credits improvement to a specific
   treatment just because the improvement followed the treatment.

   H. K. Beecher's seminal paper "The Powerful Placebo" (Beecher 1955) is
   among the most frequently cited and was undoubtedly responsible for the
   double-blind study design having been adopted as the universal
   standard. Beecher reported on twenty-six studies and arrived at an
   average placebo response rate of 32.5 percent. From this figure comes
   the often cited statement that a fixed fraction (one-third) of the
   population responds to placebos. But this is a myth. A recent paper
   (Roberts et al. 1993) concluded that "under conditions of heightened
   expectations, the power of nonspecific effects (placebos) far exceeds
   that commonly reported in the literature."

   The paper, "The Power of Nonspecific Effects in Healing," is
   fascinating. The authors analyzed data for treatments that met the
   following criteria:
     * strong positive reports by at least two groups of investigators;
     * at least one well-controlled negative report;
     * the treatment had been abandoned as ineffective; and
     * data from a major portion of the positive studies were presented in
       a manner that permitted reliable classification into categories of
       excellent, good, or poor outcomes.

   The treatments that were studied included: glomectomy (the surgical
   removal of a small, normal mass of tissue called the carotid body that
   is found on the carotid artery) for the treatment of asthma; levamisole
   (an immunomodulatory drug) for the treatment of Herpes Simplex Virus
   (HSV); organic solvents (ethyl ether and chloroform), also for HSV; and
   gastric freezing for duodenal ulcers. In all the cases the doctors and
   the patients expected the treatments to work. The results for all the
   positive studies combined showed an excellent or good outcome in 69.8
   percent of the almost seven thousand cases studied. These results led
   to the conclusion that a treatment outcome "is always due to some
   interactive combination of specific and nonspecific effects."

   Research also illustrates how difficult it is to separate valid
   treatments from apparently valid ones. In other words, we're never
   without some level of nonspecific effects.

   A number of other myths are associated with placebos. Try to answer the
   following questions:
    1. Does a positive response to a placebo mean the patient's problem is
       imaginary?
    2. Does a patient have to believe in the therapy for a placebo effect
       to occur?
    3. Are placebos harmless?

   The answer to all three questions is no. Placebo responses can occur in
   patients with real disorders; the subjective symptoms can resolve while
   the objective ones remain. Belief in the treatment only appears to
   explain a portion of the placebo effect (Jarvis 1990). It appears that
   belief, operant conditioning, and suggestibility all play important
   roles. In an interesting experiment, a man experienced pain and
   exhibited marked depression of a specific part of his heartbeat while
   being monitored by an electrocardiogram (ECG) machine during a
   treadmill diagnostic test. This occurred at a treadmill setting of 44.
   For a second test, when the treadmill number was miscounted so that the
   patient exercised less, he exhibited the same pain and ECG depression
   as at the setting of 44 (Jarvis 1990). This dramatically demonstrates
   the power of suggestion.

   Contrary to popular belief, placebos can be harmful. Placebo responses
   can "teach" chronic illness by confirming and/or reinforcing the
   delusion of imagined disease (Jarvis 1990). Patients can become
   dependent on nonscientific practitioners who employ placebo therapies.
   Such patients may be led to believe they're suffering from imagined
   "reactive" hypoglycemia, nonexistent allergies and yeast infections,
   dental filling amalgam "toxicity," or that they're under the power of
   Qi or extraterrestrials. And patients can be led to believe that
   diseases are only amenable to a specific type of treatment from a
   specific practitioner. On the other hand, the practitioner can also be
   blinded to the real disease because of being convinced that the
   patient's condition is only imagined. Jarvis (1990) reminds us that
   "for both patient and practitioner to be blind to the clinical
   realities is an unacceptable version of the 'double-blind.'"

   The use of placebos can undermine the doctor-patient relationship by
   requiring deception on the part of the caregiver. Consumer advocate
   Stephen Barrett has explicit reservations concerning overreliance on
   the placebo effect in clinical practice: "I am against people being
   misled. The quack who relies on a placebo effect is also pretending he
   knows what he is doing-that he can tell what is wrong with you and that
   he has effective treatment for just about everything . . . he is
   encouraging people to form lifelong habits of using things they don't
   need" (Barrett 1977).

   In addition, placebos "need not always be beneficial and may be frankly
   toxic: dermatitis medicamentosa and angioneurotic edema (allergic-type
   reactions) have resulted from placebo therapy. More subtle but equally
   important negative placebo effects must occur when the physician by
   virtue of a moment of inattention, a raised eyebrow, or a transient
   look of disgust, loses the trust of his patient" (Bourne 1991).

   Paracelsus (Swiss alchemist and physician 1493-1541) wrote: "You must
   know that the will is a powerful adjuvant of medicine." It is
   imperative that skeptics recognize the wisdom and warnings inherent in
   this statement.

References

     * Barrett, S. 1977. Health frauds and quackery. FDA Consumer
       11:12-17.
     * Beecher, H. K. 1955. The powerful placebo. JADA 159:1602-1606.
     * Bourne, H. 1991. Unrecognized therapeutic measures, including
       placebo. In Clinical Pharmacology, ed. by K. L. Melmon and H. F.
       Morrelli. New York: Macmillan.
     * Jarvis, W. T. 1990. Dubious dentistry: A dental continuing
       education course. Loma Linda University, Loma Linda, Calif.
     * Roberts, A. H., D. G. Kewman, L. Mercier, and M. Hovell. 1993. The
       power of nonspecific effects in healing: Implications for
       psychosocial and biological treatments. Clinical Psychology Review
       13:375-391.

John E. Dodes

   John E. Dodes is the president of the New York Chapter of the National
   Council Against Health Fraud, and the only dentist on the New York
   State Department of Health's Health Fraud Advisory Board. His new
   consumer book, The Whole Tooth, written with Dr. Marvin Schissel, is to
   be published by St. Martin's Press in 1997.

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   One of the most puzzling facts of medicine is the placebo effect:
   namely, that a substantial proportion of patients report feeling better
   after receiving a "sugar pill," or some other treatment with no known
   benefit for their illness. Between 30 - 60% of patients with illnesses
   ranging from arthritis to depression report a substantial improvement
   in their symptoms after receiving a placebo. It is not clear that
   placebo can "cure" any illness, but the power of the placebo effect in
   improving symptoms and reducing suffering is impressive.

   Our research program is designed to help us understand how placebo
   effects occur and how to distinguish between people who are exhibiting
   a placebo response and those responding to the specific treatment (e.g.
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   those seen during medication treatment. You can read the press release
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   American Journal of Psychiatry. This work was replicated and extended
   in our December 2004 publication in Psychopharmacology.

   More recently, we have reported that brain function changes during a
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Respectful Insolence

The “myth” of placebo effects

   Posted by Orac on March 21, 2013
   (90)
   More »

   Heidi Stevenson amuses me.

   The reasons are legion. Be it the time when Heidi lectured scientists
   on anecdotal evidence (which she values far more highly than
   scientists, of course, declaring it the “basis of all knowledge”);
   launched a vile and nonsensical attack on Stephen Barrett; argued
   against prior plausibility with using a straw man argument so massive
   that if it were set on fire (which she did) it could be seen from
   space; or made an even more idiotic argument to try to “prove” that
   wi-fi signals and EMF cause autism, Heidi never fails to deliver the
   stupid in mass quantities of black hole density. Of course, what does
   one expect? Stevenson is a homeopath, after all. Anyone who can believe
   the pseudoscience and wishful thinking that underlies homeopathy is
   already almost by definition lacking more than a little something in
   the logic department. Certainly she’s missing a lot in the science
   department as well. All of this is why she amuses me so much and why on
   occasion when she catches my attention I feel like laying down just a
   touch of that not-so-Respectful Insolence that you all know, love, and
   crave. True, sometimes I feel as though I’m slumming, but in actuality
   Stevenson’s very useful in that she is very good at demonstrating
   logical fallacies and misunderstandings of science that provide a
   number of what we in the science and skeptical blogging biz like to
   refer to as “teachable moments.”

   Yesterday, Stevenson provided yet another in her long line of teachable
   moments in the form of a post entitled, Busting the Placebo Myth:
   Placebos Don’t Cure. In it, she rails against us nasty, pointy-headed
   skeptics who point out that placebos only make people think they feel
   beter and don’t actually make people better. The hilarious thing is
   that she uses studies that I’ve blogged before in order to come to
   exactly the wrong conclusion. Stevenson’s great that way. Even better,
   since I’ve blogged these studies before, I can try to get a handle on
   my logorrhea in this post. Well, no I can’t. As Hans Solo said, “Hey,
   it’s me.” I can keep it short for a while, but sooner or later the
   logorrhea always returns. Whether it will return during this post or
   not, you’ll just have to keep reading to find out. We’ll have to see if
   it works out. Either way, it’ll be entertaining and educational. I
   promise.
   Clearly, Stevenson is really, really peeved at the criticism of her
   quackery that labels it as “placebo medicine.” Of course, as I’ve
   discussed time and time again the vast majority of so-called
   “complementary and alternative medicine” (CAM) or, as it’s called now,
   “integrative medicine,” is based on placebo medicine and the idea that
   wishing makes it so. I realize that Stevenson doesn’t like that, but
   that’s just tough. Reality is reality, quacks are quacks, and science
   is science, and never the three shall meet at the same time. In any
   case, Stevenson starts out:

     One of the most frequent epithets tossed at people who make claims
     of alternative medicine is that it’s just the placebo effect. But
     that is based on the myth that placebos can cure. The reality, as
     clearly documented by science, is that they don’t. So the skeptics
     base their favorite claim on a myth, not reality, and most assuredly
     not on science.

   Stevenson then goes on a brief rant about what she refers to as the
   “myth” of placebos, including that placebos don’t heal, that placebos
   are a “complete flop,” that no one is ever “cured” by a placebo. Of
   course, these are not myths. They are more or less true, except for the
   second one. Even skeptics don’t say that placebos area a “complete
   flop.” we’re all for studying placebo effects and determining ways to
   maximize it during treatment with actual…oh, you know…effective
   medicine. What we don’t approve of is relying on placebo effects alone,
   which is what the vast majority of CAM is. Not only is it unethical to
   lie to patients that way, but it doesn’t help the pathophysiology of
   the condition being treated. To most ethical, science-based physicians,
   that’s a double whammy against using placebos that can’t be overcome.
   The first funny thing is that, in order to make her point, Stevenson in
   essence buys into this point. Rather than trying to argue for the
   “pwoerful placebo,” some like to put it, or The Secret, as I like to
   put it, she actually does her best to rubbish placebo effects as
   insignificant as an introduction to arguing that any condistions
   “cured” by alternative medicine couldn’t possibly have been cured by
   placebo effects. This is a straw man even bigger than the
   aforementioned straw man whose demolition with napalm-grade flaming
   stupid could be seen from space. That straw man is that skeptics
   dismiss “healing” by alternative practitioenrs as being due to placebo
   effects.

   The second funny thing about this article is that Stevenson relies
   largely on Ted Kaptchuk, the Harvard high priest of acupuncture studies
   in quackademic medicine in the United States. Just type his name into
   the search box of this blog, and you’ll see that I’ve discussed him
   many times before in the context of how the results of his studies do
   not show what he concludes that they show or what they are claimed to
   show by advocates and the press. It thus amuses me greatly that both of
   the studies that Stevenson chooses to use to demonstrate her point are
   ones that I wrote. One I wrote about a couple of years ago—along with
   practically every skeptical blogging doc out there. Amazingly,
   Stevenson more or less correctly interprets the study:

     The study used FEV1, Forced Expiratory Volume in 1 Second, to
     measure effectiveness. The graph on the left clearly shows that the
     drug placebo and sham acupuncture (another kind of placebo) had no
     curative effect, as they didn’t cause any change in FEV1. However,
     in the graph on the right, you can see that the subjects felt that
     both the drug placebo and sham acupuncture were nearly as effective
     as the actual drug, albuterol.

     Two things are clearly demonstrated. One is that a patient’s sense
     of well-being can readily be skewed by belief. The other, though, is
     that placebos have absolutely no healing benefit.

   It kind of creeps me out that that’s more or less what I concluded in
   my analysis of this particular study. She also discussed the infamous
   “placebos without deception” study by Kaptchuk that was sold as
   evidence that you don’t have to lie to patients in order to invoke
   placebo effects but, when examined more closely, shoed nothing of the
   sort. For a moment, I was wondering if I was losing my sanity. What
   kept me from getting too worried was the tone of the article, very
   confrontational to science-based medicine and skeptics. Also, the
   sarcasm. Given how good I’ve become at not-so-Respectful Insolence, I’m
   very much in tune with other people’s sarcasm, and Stevenson was being
   quite sarcastic. I knew there had to be a reason and that there would
   be a payoff, and I wasn’t wrong:

     The claims by skeptics that the placebo effect can explain away any
     and all results of alternative medicine are pure bunk. They’re based
     on a false belief, the idea that the placebo effect is so powerful
     that it can cure. That is nothing but a myth. They can palliate—make
     people feel better—but never cure.

     The placebo effect can be powerful in terms of people’s sense of
     health and welfare. However, no one is ever healed by a placebo.
     Therefore, when someone is actually cured by an alternative
     treatment, the false bravado of the skeptics, who invariably come
     streaming along shouting about the placebo effect, usually full of
     condescension and insults, is nothing more than that—hot air based
     on a belief that is founded only in myth.

     The simple fact is that placebos cannot cure. So those claims of
     successful treatment for diseases that are not subjective—such as
     cancer, autism, mastitis in cattle, skin conditions, or any
     other—cannot be denied with that off-hand line, “But, my dear, it
     can easily be explained by the placebo effect.” No, it cannot.

   And there’s the flaming straw man.

   In fact, I challenge Heidi Stevenson to produce an example of a skeptic
   dismissing an “alternative” therapy story in which cancer, autism,
   mastitis in cattle (where did that one come from?), or skin conditions
   were “cured” by alternative medicine as being just due to placebo
   effects? Cancer is a very good example. Many are the times that I’ve
   spoken about alternative medicine “cancer cure” testimonials, going all
   the way back to the very beginning of this blog and continuing forward.
   What you’ll find are explanations of the potential for spontaneous
   remission, what the difference between adjuvant therapy and curative
   therapy is and how alternative cancer cure testimonials confuse them,
   and a variety of other explanations. One thing you will not find is me
   trying to dismiss these cancer cure testimonials as being due to
   placebo effects. Indeed, if I ever saw a skeptic trying to do that,
   that skeptic might well himself become the target of a little bit of
   not-so-Respectful Insolence. And he’d deserve it, too.

   In a way, maybe Stevenson can be forgiven for thinking that the only
   arguments skeptics have against alternative medicine is to label it all
   as “placebo.” She is, as has been noted before, a homeopath, and if
   there is a form of “medicine” that is nothing more than pure placebo,
   it’s homeopathy. However, that doesn’t mean that pointing to placebo
   effects is the only weapon in the skeptical arsenal against the
   unscientific and pseudoscientific claims of alternative medicine. it is
   but one of many, and it’s generally only invoked—and correctly so—when
   claims about the ability of this quackery or that to relieve pain,
   anxiety, or other subjective symptoms. No one—and I mean no one—tries
   to dismiss alternative cancer cure testimonials, for example, as mere
   placebo effect. Ditto the issue of autism, the “cure” of which is
   generally discussed in terms of development (autism is a condition of
   developmental delay, not stasis) and not placebo effects. Improvements
   in skin conditions are usually explained by how such conditions often
   wax and wane.

   In the end, I can’t help but wonder how Stevenson’s fellow quacks will
   react to her dismissing the ability of placebo effects to cure as a
   “myth.” Somehow I suspect they won’t be so happy. At least, Mike Adams
   won’t.
   Keywords: Heidi Stevenson, homeopathy, placebo, quackery
   (90)
   More »

Comments

    1. #1 Heliantus
       March 21, 2013

     Busting the Placebo Myth: Placebos Don’t Cure
       Can we quote her next time someone proposes to harness the placebo
       effect?
    2. #2 palindrom
       March 21, 2013
       Crowd: We need a cure! We need a cure!
       Dr. Hibbert: Ho ho ho. Why, the only cure is bedrest. Anything I
       give you would be a placebo.
       Woman: [frantic] Where can we get these placebos?
       Man: (points at truck) Maybe, there’s some in this truck!
       (Crowd knock over truck and a box of killer bees from it break out
       and attack the crowd. A man, thinking the bee is a vaccine, takes
       it and swallows it)
       Man: I’m cured! I mean, ouch!
       — The Simpsons, “Marge in Chains”
    3. #3 palindrom
       March 21, 2013
       On that Simpsons quote — the crowd was upset because the dread
       Osaka Flu was going around.
       Ironically, the Osaka Flu arrived in Springfield from Japan in
       boxes of “Juice Looseners”, which had been pushed on TV in an
       infomercial by quack Doctor Nick Riviera and washed-up movie star
       Troy McClure.
       Homer and others had ordered them: (Homer: “Gotta get a juicer!
       Won’t get chest pains from answering the phone any more!”); the
       juicers were packed by hyperconscientious Japanese workers working
       sick, and the rest followed.
       And that wasn’t even the main storyline.
    4. #4 Dangerous Bacon
       March 21, 2013
       Orac can sneer at homeopaths, but I bet he’s never cured a case of
       bovine mastitis.
    5. #5 Mephistopheles O'Brien
       March 21, 2013
       Actually, Stevenson’s argument is pretty good:
       1. Placebos don’t cure anything, they just make people feel better
       sometimes.
       2. Alternative medicines cure things.
       ergo, Alternative medicines are not just placebos.
       Now, if she could only prove statement 2 were true, she’d have a
       case.
    6. #6 Leigh Jackson
       March 21, 2013
       So Stevenson get’s placebos but doesn’t get that CAM is a synonym
       for placebo. So funny one just has to cry.
       Compare and contrast her take with that of Jeremy Howick of the
       Centre for Evidence-Based Medicine (University of Oxford) in todays
       Times: “Placebos work… if doctors are happy prescribing them, we
       should take them.”
       Placebos don’t have to be deceptive to be clinically effective says
       Howick, quoting Kaptchuk’s “open” placebo study for irritable bowel
       syndrome.
       With Kaptchuk it seems like you pays your money and you makes your
       choice.
    7. #7 Denice Walter
       March 21, 2013
       @ Helianthus:
       Ha. Some woo-meisters speak as if ‘placebo’ incorporated a species
       of healing energy that is unleashed whenever woo transpires
       allowing the body to heal itself perhaps through the liberation of
       its own energy in resonant response. In other words, sympathetic
       magic.
       In other placebo-centric news:
       AoA has been in an uproar about a new study that reveals (gasp!) a
       2% autism rate ( a phone survey/ see LBRB).
       Jake strikes back:
       ” And of course, Roy Richard Grinker is bringing dow the reputation
       of GW by using his academic stature to deny the autism epidemic
       once again”.
       I’m sure he actually believe that.
    8. #8 Denice Walter
       March 21, 2013
       I lost comments due to an error on my part:
       Helianthus:
       Some woo-meisters speak as if placebo were a means to liberate the
       healing energy that naturallyresides within the body. Probably
       through resonance. In other words, magic.
       In other news:
       AoA carries on about a new autism rate of 2 % based on a PHONE
       survey.
       Jake complains about Prof Grinker destroying GW’s reputation by
       ‘epidemic denialism’.
    9. #9 sophia8
       March 21, 2013

     mastitis in cattle (where did that one come from?)
       Can Homeopathy Cure Mastitis in Cows?
   10. #10 Denice Walter
       March 21, 2013
       Stevenson writes at Green Med Info and Gaia Health**.
       Here’s an article from the latter ( 2010):
       ” Big Pharma Scores Big Win: Medicinal Herbs Will Disappear in EU”
       She cites Verkerk ( ANH).
       ** talk about swampish sinkholes of unreason.
   11. #11 Dangerous Bacon
       March 21, 2013
       Can you do a phone survey of cows?
       (lows softly)
   12. #12 lilady
       March 21, 2013
       “….mastitis in cattle (where did that one come from?)”
       You’ve gotta love YouTube for testimonials….
       http://www.youtube.com/watch?v=PmI_Mb_bRoo
   13. #13 Denice Walter
       March 21, 2013
       There is one thing about placebos:
       when you actively pursue a treatment, follow a diet, execise as
       well as PAY for these interactions, you are motivated to believe
       that they have an effect.
       If you invest time, thought, energy, effort and money in something,
       you want to believe in it.
   14. #14 Todd W.
       http://www.harpocratesspeaks.com
       March 21, 2013
       @Denice Walter

     AoA carries on about a new autism rate of 2 % based on a PHONE
     survey.
       Well, they can criticize the CDC for conducting a phone survey,
       because they’re the CDC and, therefore, wrong. But when AoA
       conducts a phone survey, even when the results don’t say what they
       want them to say, the survey is slamdunk evidence that vaccines
       cause autism.
       Then again, in the same breath they criticize the study for being a
       “mere” phone survey, they also go on and on about “ZOMG! 1 in 50
       now!” So is the survey reliable or not?
       Then there’s also Teresa Conrick’s “research” about Alzheimer’s and
       Autism sharing a connection: other than both starting with “A”,
       seniors and kids both get the flu vaccine! The horror! Right? Then
       again, Ms. Conrick is also the one who blamed thimerosal for her
       daughter’s eyes (which were blue at birth) changing color to a
       brownish green, rather than understanding that babies are commonly
       born with blue irises that change color as they age.
   15. #15 Denice Walter
       March 21, 2013
       @ Todd W.:
       Ms Conrick has produced the most baroquely inelegant and convoluted
       hypotheses that I have ever seen.
       That must be some osrt of an accomplishment.
   16. #16 Todd W.
       http://www.harpocratesspeaks.com
       March 21, 2013
       @Denice Walter
       Her technique can be summed up thusly: “! Research! Dots! Connect
       them!” and then she drops the mic and walks off stage.
       And on-topic, when, oh when!, will people stop citing Kaptchuk?
       Especially that study purporting to look at “not misleading people
       about placebos” that actually did mislead them?
   17. #17 Todd W.
       http://www.harpocratesspeaks.com
       March 21, 2013
       Whoops. Forgot that pointy brackets are HTML code delimiters. That
       should have been “[Random quotes that sound scary]! Research! Dots!
       Connect them!”
   18. #18 Bronze Dog
       March 21, 2013
       The absolute most I think I’d ever say about cancer and placebos is
       that a placebo might make the patient feel better about the
       subjective symptoms. It wouldn’t do anything whatsoever about the
       cancer itself or any of the objectively measurable symptoms. If the
       cancer coincidentally went into remission, I wouldn’t give the
       placebo any credit for it, but alties probably would, since they so
       commonly rely on the post hoc fallacy.
   19. #19 Krebiozen
       March 21, 2013
       Stevenson’s article is one of the most jaw-droppingly dumb I have
       read in a long time. Homeopaths and acupuncturists make a living by
       persuading patients to mistake a placebo effect for a real effect
       of their treatment.
       A paper on placebo use came out today:Placebo Use in the United
       Kingdom: Results from a National Survey of Primary Care
       Practitioners

     Placebo use is common in primary care but questions remain about
     their benefits, harms, costs, and whether they can be delivered
     ethically. Further research is required to investigate ethically
     acceptable and cost-effective placebo interventions.
   20. #20 Krebiozen
       March 21, 2013
       The press release from Southampton University about that paper is
       also interesting:

     “This latest study with the University of Oxford demonstrates that
     doctors are generally using placebos in good faith to help
     patients,” says Professor George Lewith, co-lead author of the study
     from the University of Southampton. “Other previous published
     studies by Southampton have clearly shown placebos can help many
     people and can be effective for a long time after administration.
     The placebo effect works by releasing our body’s own natural
     painkillers into our nervous system. In my opinion the stigma
     attached to placebo use is irrational, and further investigation is
     needed to develop ethical, cost-effective placebos.”
       That’s not quite how I see placebos. Has it really been
       demonstrated that placebos work, “by releasing our body’s own
       natural painkillers into our nervous system”? I thought much of
       what is called “the placebo effect” isn’t really an effect at all,
       but an illusion collectively caused by regression toward the mean
       and various cognitive biases. If we are talking about subjective
       changes due to suggestion, perhaps we should call them that, and
       abandon the term “placebo effect” altogether as hopelessly
       misleading.
   21. #21 Mike Olson
       Sherrard, Illinois
       March 21, 2013
       Hi there! Lay person here. I have a liberal arts degree and worked
       as a lab tech in the Navy. I read popular science books, (some of
       which various science bloggers have written) and “Scientific
       American.” Just trying to give you an idea of my background. I read
       a book called something like, “Hacks, Quacks and Big Pharma
       flacks.” Which seemed to truly contradict the notion that placebos
       did nothing to help a person feeling better. Simply believing a med
       or procedure would work better or make a person feel better
       actually induced immunological responses…according to the book.
       Responses to name brand drugs were quicker than generics, as I
       recall.
       I don’t bring this up to contradict any argument against snake oil
       salesmen( or women), but rather to suggest that a premise of,
       “Placebos just make a person feel better it they don’t make them
       better,” is probably wrong. At least from what this ill informed,
       somewhat literate lay person has read.
       Can anyone clarify this for me?
   22. #22 Narad
       March 21, 2013

     mastitis in cattle (where did that one come from?)
       Taken apart by SkeptVet here.
   23. #23 Alan Kellogg
       Soon to be repurposed City Library
       March 21, 2013
       Drugs don’t heal people, drugs make it easier for people to heal
       themselves.
   24. #24 Beamup
       March 21, 2013

     I read a book called something like, “Hacks, Quacks and Big Pharma
     flacks.” Which seemed to truly contradict the notion that placebos
     did nothing to help a person feeling better. Simply believing a med
     or procedure would work better or make a person feel better actually
     induced immunological responses…according to the book.
       You can measure certain physiological responses, certainly. What
       nobody’s yet been able to do convincingly is show that they are
       MEANINGFUL rather than simply measurable.
       The classic example is that acupuncture produces changes in the
       brain visible in an fMRI. Well, sure. The brain registers that it’s
       feeling something. Does this mean that acupuncture actually does
       anything meaningful? No, in order to say that you’d have to measure
       an actual clinical outcome.
       In short, saying “placebo works, look, I can measure a change in
       this lab value” can be accurately translated as “look, placebo
       doesn’t really do anything, since the most effect I can find is in
       some random lab value rather than talking about a clinical result.”
   25. #25 St Thomas
       March 21, 2013
       https://www.youtube.com/watch?feature=player_embedded&v=ntWO7jnOcWE
       How placebo prescribing may work in practice.
   26. #26 Leigh Jackson
       March 21, 2013
       @ Krebiozen, 18,19
       The oh-so-cautious official conclusion of the study regarding the
       scientific and ethical status of placebos belies the two co-leads
       loud and laudatory public endorsement of GPs use of placebos.
       The only unequivocal thing the study recommends is further research
       on placebos. Hardly surprising given that Lewith heads one of the
       two co-funders of the study.
       “The Southampton Complementary Medical Research Trust was
       specifically established to raise money and aid the research
       development at the Complementary Medicine Research Unit at the
       University of Southampton.”
       http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1193549/
       And turkeys do not vote for Christmas:
       http://www.drrogersprize.org/files/bio-lewith.php
   27. #27 Denice Walter
       March 21, 2013
       I would so totally NOT go with concept of the placebo effect being
       an expression of endogenous opiates.
   28. #28 S
       March 21, 2013
       Doctors that prescribe placebos to their patients should be paid
       with placebo cash. Turnabout is fair play, right?
   29. #29 Krebiozen
       March 21, 2013
       Mike Olson,

     Simply believing a med or procedure would work better or make a
     person feel better actually induced immunological
     responses…according to the book.
       I think this is a common misconception. Most clinical trials
       compare an active treatment to a placebo, and it is easy to assume
       that any measured changes in patients in the placebo arm of the
       study are caused by the placebo. If you look at clinical trials
       that include a ‘no treatment’ arm, you will usually find that
       patients who have no treatment do just as well as those given a
       placebo.
       My favorite example is this study which is often cited as evidence
       that sham knee surgery (making an incision and then simply sewing
       it back up) is as effective as lavage (washing out the joint) and
       debridement (basically scraping out the joint), thus demonstrating
       the awesome power of the placebo. However:

     The authors found that all three treatment groups fared equally:
     each reported subjective symptomatic relief, but no objective
     improvement in function was noted in any of the groups.
       In other words, none of these interventions had any objective
       effect on knee function, only on subjective assessment of pain, and
       we don’t even know if patients given no treatment at all might have
       reported a similar reduction in pain over time, since the study
       lacked a no treatment group. The placebo wasn’t awesome at all, it
       was as useless as the surgical interventions.
       Similarly, you can find lots of studies of alternative therapies
       that are essentially placebos, for example therapeutic touch, that
       have no consistently measurable effect on an objective measure, for
       example, wound healing, as in this study. If you can find a study
       that shows a placebo has a consistent and significant objectively
       measurable effect as compared to no treatment I would be very
       interested.
   30. #30 Krebiozen
       March 21, 2013
       Leigh Jackson,
       Thanks for the information on the authors of that placebo study,
       which confirms my suspicions.
   31. #31 Denice Walter
       March 21, 2013
       Interestingly, one of the winners of the prize in 2007 was
       Abram Hoffer of Orthomolecular fame.
       If his ideas win a prize, I’d hate to read what the runners up and
       losers promulgate.
   32. #32 Mike Olson
       March 21, 2013
       Krebiozen
       Thank you. What you’ve reported sounds very similar to what was
       written in the book. I’d thought it had been mentioned in that same
       book, however, that if persons had some sort of infection and were
       given antibiotic, their immune system would respond with a given
       set of antibodies. Over time, even if they were given a placebo
       that appeared similar to the antibiotic, their bodies would still
       respond with the same antibodies.
       It seemed like an odd effect…perhaps I read it wrong. The author
       did indicate that essentially all persons are susceptible to the
       placebo effect and it had nothing to do with being “weak minded” or
       some defect of character. Again your response seems to be in the
       same vein as what he had written.
   33. #33 Will Bradbury
       March 21, 2013
       https://sphotos-b.xx.fbcdn.net/hphotos-frc3/253777_623247231024744_
       1877166513_n.jpg
   34. #34 Narad
       March 21, 2013
       @Will: That tangentially reminds me that back when I was an
       undergrad, we were sneaking Zilog chips to Roald Sagdeev.
   35. #35 lkr
       March 21, 2013
       Homeopathic cures for mastitis in cattle
       PLUS
       Raw milk for ADD, allergies, colds, etc. etc. in unvaccinated kids
       — what could go wrong?
   36. #36 Darwy
       Røde grøde med fløde
       March 22, 2013
       A telephone survey for cows?
       Let me fire up the grill… I think we’re having steaks tonight…
   37. #37 herr doktor bimler
       March 22, 2013
       Homeopathic cures for mastitis in cattle
       I am waiting for the acupuncture version. Tell you want, *you*
       stand behind Buttercup and stick the needles in, *I’ll* watch from
       a safe distance.
   38. #38 Martin
       March 22, 2013
       HDB: That sounds likely to result in the joke whose punchline is
       “If you can persuade my wife I was going to milk that cow, I’ll buy
       a tractor from you.”
   39. #39 Krebiozen
       March 22, 2013
       Mike Olson,

     Over time, even if they were given a placebo that appeared similar
     to the antibiotic, their bodies would still respond with the same
     antibodies.
       I suspect you mean ‘antigen’, not ‘antibody’, and I think you are
       referring to learned histamine release. Our immune system does seem
       to be susceptible to Pavlovian conditioning to some extent – this
       study found you can condition a rat’s immune systems to respond to
       an audiovisual cue, for example. It’s interesting, but I don’t see
       how that means placebos ‘work’ in the sense of having an objective
       effect on the body. It sounds to me as if the author of that book
       is looking for explanations of how placebos ‘work’, when the best
       evidence suggests that they don’t.
   40. #40 Krebiozen
       March 22, 2013
       Maybe I should declare myself as a lapsed placebo-effect believer –
       a few years ago I was hopeful that the field of
       psychoneuroimmunology would revolutionize medicine, but I have been
       sorely disappointed.
       Another example I find interesting is in a TV show, ‘Miracles For
       Sale’ (blocked in the UK) in which Derren Brown’ teaches a man many
       of the tricks of faith healing. The section I am thinking of is
       where he goes out on the street and ‘heals’ people – you will find
       it starting at 56:38 – the very first person who is ‘healed’
       reports a pain in his leg reduces from a level of 10 down to zero.
       That’s pure suggestion, but I would be willing to bet that there
       was no objective improvement in his leg. I think that’s the extent
       to which placebos ‘work’.
       As to whether this is clinically useful, I think that’s debatable.
       In the sense that a placebo may persuade a patient to go away and
       stop bothering a doctor, then perhaps they have a use. On the other
       hand prescribing antibiotics for viral infections as a sort of
       placebo has contributed to the spread of resistant bacteria, and
       feeling better when you’re not can be dangerous, in asthma for
       example.
   41. #41 Krebiozen
       March 22, 2013
       To confuse matters I wrote above in #39, “I suspect you mean
       ‘antigen’, not ‘antibody’”, when I meant, “I suspect you mean
       ‘antigen’, not ‘antibiotic’. Hopefully you got my drift.
   42. #42 Dr. Nancy Malik
       Gurgaon, India
       March 22, 2013
       Placebo is an inactive dummy/inert pill (substance such as
       lactose/saline which do not alter the disease condition) prescribed
       to the patient for enhancing he non-specific effects of the
       treatment and/or the doctor does not want to disturb the course of
       action of previously prescribed medicine till it completes its own
       run.
       Ref:
       http://drnancymalik.hpathy.com/2012/08/17/understanding-evidence/
   43. #43 Bronze Dog
       March 22, 2013
       One additional aspect I think is worth mentioning when it comes to
       subjective improvement in pain and the like: Some people are
       naturally polite, encouraging, or adverse to confrontation. If they
       see a doctor working to help them, they might report improvement,
       even if there is none, to avoid impugning the doctor’s competence.
       That’s probably one of the more subtle components of the placebo
       effect: Some patients will lie, understate, or exaggerate to make
       the doctor feel better.
       Add in the popular altie methods of blaming the victim, and some
       will feel pressured to always report improvement and cover up
       symptoms in order to avoid being shamed by their quack, guru,
       and/or altie friends.
   44. #44 Krebiozen
       March 22, 2013
       I see we have been subjected to a no-doubt hit-and-run visit from
       Nancy Malik who has been described as a “homeopathy shill,
       fact-blind delusional crank and serial comment spammer” . I suppose
       that’s appropriate for a post about placebos.
   45. #45 Beamup
       March 22, 2013
       @ Nancy:
       That is not accurate. The concept of a placebo is very much
       broader. A nice chat with a “practitioner” who assures you they can
       fix anything that’s wrong, for example, would very much qualify by
       the standard definition.
       Of course, I can’t expect anyone who claims to practice
       “evidence-based homeopathy” to understand that. The only legitimate
       evidence-based view of homeopathy is that it is completely bogus
       and does nothing… because it is, in fact, a placebo.
   46. #46 Krebiozen
       March 22, 2013
       Bronze Dog,

     Some patients will lie, understate, or exaggerate to make the doctor
     feel better.
       I agree, and none of these are helpful to the patient in the
       slightest. They may even discourage her/him from giving the doctor
       important information about her/his condition.
   47. #47 Todd W.
       http://www.harpocratesspeaks.com
       March 22, 2013
       Guys, you’re being too hard on Nancy Malik. You see, she’s
       describing homeopathy: an inactive dummy/inert pill (e.g., lactose)
       that does not alter the disease condition.
   48. #48 Tom Herling
       March 22, 2013
       Audio engineers will often rely on placebo effect to placate some
       impossible client who, during a recording session wants more
       “purple”–our code for some inaudible but highly desired effect.
       So knowing that an audio console usually has several redundant
       controls, we show our client a knob that does nothing, and let them
       operate it so they have control over the amount of “purple.” Then
       we rehearse a couple of times (“Did you get it?” we ask, “Almost,
       let’s try it again,” says the client) until we get it “right” and
       can head home, but only after we’ve reached our desired amount of
       billable hours.
   49. #49 Leigh Jackson
       March 22, 2013
       Re: placebo, qua endogenous opiates cum psychoneuroimmunology cum
       clasical conditioning.
       Would be interested to hear views on the work of Fabrizzio
       Benedetti. Typically, for example:
       http://rstb.royalsocietypublishing.org/content/366/1572/1790.long
       In similar vein, Zubieta/Stoler:
       http://www.ncbi.nlm.nih.gov/pubmed/19338509?dopt=Abstract
   50. #50 Krebiozen
       March 22, 2013
       Leigh Jackson,
       I’ll read and respond to the material you linked to in more detail
       in a day or two when I have had time to ponder it properly, as it’s
       an area that still greatly interests me.
       Briefly, placebos do appear to have an effect on perceived pain,
       but I wonder if that is as significant as the authors you refer to
       think. If I stomp on someone’s foot it may increase their endorphin
       levels and/or distract from a pain elsewhere in their body, and
       this effect would also probably be blocked by an opiate antagonist
       like naloxone. I suspect the effect of placebos on subjectively
       assessed conditions such as pain may be similar to this. The
       important question is whether this is clinically useful, and I’m
       not sure it is.
   51. #51 Politicalguineapig
       March 23, 2013
       Here cookie
   52. #52 Leigh Jackson
       March 23, 2013
       Krebiozen,
       Thanks. We think alike. Howick and Lewith speak as if it’s all a
       done deal: placebos do produce clinical benefits and the mechanism
       is understood. They are calling on the GMC to allow free
       prescription of placebos on the basis that it already happens and
       that research like Benedetti’s validates the practice.
       I trust that the GMC has a fuller picture than I do on the overall
       state of science in these matters, but my own (non-physician,
       non-researcher) position is profoundly sceptical.
   53. #53 Melissa G
       March 23, 2013
       So, speaking of placebo effects, and it’s evil Mirror Universe
       twin, nocebo here’s a Slate article about wind farms and people who
       live near them freaking out.
       My question is, why don’t people ever ascribe HEALTH benefits to
       stuff like this??? Why isn’t it ever, “Infrasound cured my cancer!”
       or “Cell phones boost your brainpower!!!” or the like? Humans seem
       to be primed to accept the negative about stuff we don’t fully
       understand, rather than the positive. I would *think* it’s maybe a
       trait that helped us survive the dangerous predators and poisonous
       new foods or something… only people seem ready to accept ANY health
       claim for weird foods that taste disgusting (goji berries, anyone?
       :P ).
       What’s up with people, y’all?
   54. #54 Krebiozen
       March 23, 2013
       Melissa G,
       You reminded me of this story from South Africa in which a
       microwave tower was alleged to be causing continuing, “headaches,
       nausea, tinnitus, dry burning itchy skins, gastric imbalances and
       totally disrupted sleep patterns”, before it was revealed it had
       been turned off for the previous six weeks. That’s another fine
       example of a nocebo effect.
       I have been reading the studies Leigh referred to, and some others,
       but I’m feeling more confused, if anything. For example they found
       that only 30-40% of patients respond to placebos, and that some
       types of placebo-induced analgesia are blocked by naloxone (which
       is an opioid inverse agonist, not an antagonist as I stated above)
       while others are not. It seems weird to me that the human body can
       produce effective endogenous analgesics, but only does so when it
       believes it has been given an external treatment. Even if this is
       correct, a drug for pain (or nausea etc.) that is ineffective in up
       to 70% of patients doesn’t seem very useful to me.
       By way of taking a step back from this, I looked at the Wikipedia
       article on placebos for the first time in several years, and found
       it very useful. It discusses, for example, Hróbjartsson and
       Gøtzsche’s Cochrane review (PMID: 20091554) of placebos that
       concludes:

     We did not find that placebo interventions have important clinical
     effects in general. However, in certain settings placebo
     interventions can influence patient-reported outcomes, especially
     pain and nausea, though it is difficult to distinguish
     patient-reported effects of placebo from biased reporting. The
     effect on pain varied, even among trials with low risk of bias, from
     negligible to clinically important. Variations in the effect of
     placebo were partly explained by variations in how trials were
     conducted and how patients were informed.
       Oddly, Wikipedia mentions criticisms of this review on the grounds
       that:

     Their meta-analysis covered studies into a highly mixed group of
     conditions. It has been reported that for measurements in peripheral
     organs the placebo effect seems to be more effective in achieving
     improvements in physical parameters (such as decreasing
     hypertension, improving FEV1 in asthma sufferers, or decreasing
     prostatic hyperplasia or anal fissure) than in improving biochemical
     parameters (such as cholesterol or cortisol) in various conditions
     such as venous leg ulcers, Crohn’s disease, urinary tract infection,
     and chronic heart failure. Placebos also do not work as strongly in
     clinical trials because the subjects do not know whether they might
     be getting a real treatment or a sham one. Where studies are made of
     placebos in which people think they are receiving actual treatment
     (rather than merely its possibility) the placebo effect has been
     observed. Other writers have argued that the placebo effect can be
     reliably demonstrated under appropriate conditions.
       Can placebos really achieve improvements such as “decreasing
       hypertension, improving FEV1 in asthma sufferers, or decreasing
       prostatic hyperplasia or anal fissure”? That question led me to
       this meta-analysis, which did a MEDLINE search for
       placebo-controlled studies on “peripheral disease processes”.
       However, I note that they state:

     Because the selected trials did not include untreated control
     groups, we restricted the dataset to trials on stable disease
     conditions, from which the effects of placebo treatments could be
     estimated by baseline changes within the placebo groups.
       No untreated control groups again, which leaves me feeling somewhat
       underwhelmed by the barely significant placebo effects on physical
       parameters they found in this and on reanalyzing Hróbjartsson and
       Gøtzsche’s data. I’m reminded of studies on homeopathy and
       acupuncture which show barely statistically significant effects
       that would be of little clinical usefulness even if they were
       reliably reproducible which they are not. I suspect many of the
       results Benedetti, Zubieta, Stoler et al have been pursuing are
       little more than artefacts in noise.
   55. #55 Leigh Jackson
       March 24, 2013
       We feel happy if good stuff happens to us: “here is something to
       help you feel better” – a placebo. The good stuff here is someone
       saying they can help us to feel better: lo and behold we do feel a
       little better! The placebo works? Nope. The good news worked –
       subjectively.
       Turn it all round: if we feel good then good stuff will happen to
       us. This is what needs to be true if a placebo is to cause
       objective clinical benefits. The good news that someone has
       something to help us makes us happy and then our feeling of
       happiness leads to our bodies repairing themselves.
       Obviously too good to be true except at the margins of bodily
       health. And then not at all easy to demonstrate.
       As for the idea of non-deceptive placebos, pull the other one. If
       you can see you are only getting a toothpick prick of your skin and
       not an acupuncture needle into your flesh you are not going to get
       the magical placebo benefit of acupuncture; now are you? For the
       magic trick to work you need deception.
   56. #56 Dr. Nancy Malik
       Gurgaon, India
       March 24, 2013
       @beamup
       Efficacy is the extent to which the medical treatment/intervention
       has the therapeutic effect under ideal test conditions
       1. Specific (pharmacological/physiological) effects: patients
       getting better because of the therapeutic effects of the medical
       treatment/intervention.
       2. Non-specific (psychological/placebo) effects:The body’s healing
       response is activated
   57. #57 Chris
       March 24, 2013
       And Nancy “robospammer” Malik, homeopathy is literally nothing and
       does not help with anything except to transfer cash from the
       patient’s wallet to your bank account.
   58. #58 Krebiozen
       March 24, 2013
       Nancy Malik,

     Non-specific (psychological/placebo) effects:The body’s healing
     response is activated
       Maybe I’m lucky, my body activates its healing response
       automatically, without any need for particular psychological
       conditions or a placebo, and rarely requires assistance from active
       outside agents. Why would the body require a placebo to persuade it
       to activate its healing response?
   59. #59 Denice Walter
       March 24, 2013
       @ Krebiozen:
       No no no!
       The placebo activates the inherent bioenergetic sytem (TM) which
       has been a-slumbering, its Xi ( qi, ki, mana, prana, life energy et
       al) obviously requires raw food, hand waving, energy medicine,
       alkaline water, chakra balancing, body work, acupuncture etc to
       inspire its get-go to get going.
       But for some reason, they never taught us about that at our
       universities. I wonder why?
       -btw- how are the foxes?
   60. #60 Khani
       March 24, 2013
       #53 I know at least one person who finds the sound of a wind tower
       to be very pleasant. Sometimes he drives out to one and sits under
       it for a while, listening–he says he finds it relaxing. Cheaper
       than therapy, right?
       Their sound remind me a bit of a washing machine, or maybe the
       ocean, personally.
   61. #61 Shay
       The Illinois upland corn prairie
       March 24, 2013
       We live six miles from a wind farm. It ruins the view but it hasn’t
       driven anybody here crazy. Yet.
   62. #62 Krebiozen
       March 24, 2013
       Denice,

     The placebo activates the inherent bioenergetic sytem [...]
       It seems like a serious design fault to me, having these marvelous
       inherent painkilling and healing abilities that only do their thing
       when we think something else is responsible.

     -btw- how are the foxes?
       There haven’t been many out and about recently; the mothers stay
       underground with their young at this time of year. We did see one
       with hair loss, probably sarcoptic mange today, the first we have
       seen in quite some time, which is worrying, though it may be an
       interloper from elsewhere, attracted by all the food available
       here.
       A few years ago we sent for some free fox mange medicine from an
       animal welfare charity, which turned out to be a homeopathic
       medicine i.e. a small bottle of distilled water. My wife used it,
       despite my skepticism, and I had to grudgingly admit it did seem to
       help though I suspect any real improvement was because of the bread
       and jam the medicine was administered on, which maybe provides some
       nutrients that the standard urban fox diet is lacking. Subsequent
       experience suggests that plenty of chicken scraps work just as
       well, which makes me wonder if it isn’t sarcoptic mange at all, but
       some sort of vitamin deficiency. Or perhaps placebos work on foxes,
       which neatly brings us back to the topic in hand.
   63. #63 Khani
       March 24, 2013
       #61 Ruins the view? I honestly find them very beautiful. I grew up
       on the prairie but I still find the flatness to be rather
       oppressive at times, and the wind towers add a nice vertical
       element, to me.
       Sometimes when I’m driving down the highway with wind towers on
       either side of my I do a little evil laughter and shout “THE
       POWER!!!! THE POOOOOWERRR!!!!!”
       … it’s a very long drive to visit my parents and with all the
       caffeine and sugar I consume to help stay awake, I get a little…
       funny.
   64. #64 Shay
       March 24, 2013
       Granted, there isn’t much of a view here unless you’re really into
       corn and soybeans. But what there is, was prettier before all them
       dang towers got put up.
   65. #65 Denice Walter
       March 24, 2013
       @ Krebiozen:
       I’m glad to hear that they’re still around…and multiplying.
       Nearby, our *suburban* foxes ( they all drive tiny black Jeeps and
       Range Rovers**) hang around a park on both banks of a small river
       that’s about 10 miles long- it has woods, sports fields and bike/
       walking paths but also borders on many backyards- which means that
       they often “interact” with humans.
       Thus, the ex feeds them expensive cat food and my friend observes
       them when riding her bike or walking her son’s dog.
       The foxes I’ve seen look quite healthy. Probably all that expensive
       cat food and whatever they steal from the garbage of wasteful
       people whose backyards they inhabit.
       Foxes- living the high life.
       ** not really
   66. #66 Khani
       March 24, 2013
       #64 Corn and soybeans here, too, and where I grew up. I still
       prefer the towers–elegant white arms reaching to the sky.
   67. #67 Narad
       March 24, 2013

     I still prefer the towers–elegant white arms reaching to the sky.
       Yah, but do they explode like proper silos?
   68. #68 Shay
       March 24, 2013
       I can’t help it, Khani…they make me think of triffids.
   69. #69 Khani
       March 25, 2013
       #67 Well, sometimes they catch fire and their arms fall off.
       #68 Hee! Well, if one ever leans over and gobbles me or the car up,
       you may say “I told you so” with complete vindication!
       Perhaps they’re merely moving their armies into position prior to
       takeover…
   70. #70 Narad
       March 25, 2013

     Well, sometimes they catch fire and their arms fall off.
       I suppose that’s something. Sadly, a blog devoted to such events
       seems to have gone dormant.
   71. #71 Krebiozen
       March 25, 2013
       Denice,

     Foxes- living the high life.
       It’s funny to think of foxes having a sort of class system that
       mirrors that of the humans they coexist with. As I have no doubt
       mentioned before, the Thames flows west to east, so historically
       the further east you went the more polluted it was, resulting in
       the west to east spectrum of descending residential desirability we
       still see in London. I would like to imagine fat foxes in the
       wealthier west London suburbs lapping up dregs of Bollinger and
       nibbling at scraps of Beluga caviar, but in reality that class of
       Englishperson prefers to pursue foxes with horse and hounds, so I
       doubt they are particularly fox-tolerant. The foxes in my manor
       walk with a Cockney strut, drop their aitches and sprinkle their
       barks with glottal stops*. They are rougher and tougher than those
       effete west London foxes, having to live on the odd scraps of a
       kebab, burger or curry discarded by a drunk, apart from those lucky
       ones that frequent our back yard.
       * Or so I like to imagine.
   72. #72 Krebiozen
       March 25, 2013
       These videos, about the construction of the London Array of wind
       turbines, are well watching if you enjoy having your mind boggled
       by impressive feats of engineering.
   73. #73 Dr. Nancy Malik
       Gurgaon, India
       March 25, 2013
       Upto the end of year 2010, there have been 270 studies published in
       106 medical journals including 11 meta-analysis, 8 systematic
       reviews including 1 cochrane review (out of approximately 20
       systematic reviews published) and 93 DBRPCT (out of approximately
       225 RCT published) in evidence of homeopathy.
       Ref:
       http://drnancymalik.wordpress.com/article/scientific-research-in-ho
       meopathy/
   74. #74 Grant
       http://sciblogs.co.nz/code-for-life/
       March 25, 2013
       Dr. Nancy Malik,
       “[…] in evidence of homeopathy.”
       … with the overall conclusion that it doesn’t work.
       I think something got left out there, eh?
       (I’ve little doubt her private list is biased to her interests, of
       course.)
   75. #75 Grant
       March 25, 2013
       (Should say doesn’t work beyond a placebo effect, but you all know
       that right?)
   76. #76 JGC
       trying to cut to the chase
       March 25, 2013
       Dr. Malik, let’s simplify the discussion as much as possible: what
       in your opinion is the single most compelling piece of evidence
       demonstrating that homeopathy is more effective at treating
       non-self-limiting illnesses than are placebo’s (i.e., that it
       actually works)?
   77. #77 Dr. Nancy Malik
       Gurgaon, India
       March 25, 2013
       @JGC
       There are different types of research. You can’t compare apples
       with oranges.
       There are meta-analysis and systematic reviews
       http://drnancymalik.wordpress.com/article/meta-analysis-and-systema
       tic-reviews/
       There are research models
       http://drnancymalik.wordpress.com/article/research-models-in-homeop
       athy/
       There are DBRPCTs and there are obeservational studies. Which one
       you like to discuss?
   78. #78 Chris
       March 25, 2013
       Awww, how cute. Robospammer Malik is referencing its own website.
       All in the effort to advertise ways to transfer cash from the
       wallets of the credulous to its own bank account.
   79. #79 MI Dawn
       March 25, 2013
       Dr Malik: We don’t want to compare apples and oranges. We are
       asking for studies published in reputable peer-reviewed journals,
       that either have been or can be reliably replicated by other
       researches.
       So unless you are claiming that your site articles are the same as
       those done in that literature I’m not going to follow your links.
   80. #80 Science Mom
       http://justthevax.blogspot.com/
       March 25, 2013

     There are different types of research. You can’t compare apples with
     oranges.
       Surely you don’t think that non-answer is going to fly here do you?
       The question was very straightforward. Please do the courtesy of
       answering it.
   81. #81 Science Mom
       http://justthevax.blogspot.com/
       March 25, 2013
       @ MI Dawn, just to let you know, “Dr.” Malik isn’t a doctor at all,
       just another homeopath crank.
   82. #82 JGC
       March 25, 2013

     There are different types of research. You can’t compare apples with
     oranges.
       You can’t compare fruit to fruit? Why not?

     Which one you like to discuss?
       As I stated previously I’d like to discuss what you believe to be
       the single most compelling study or piece of evdence demonstrating
       homeopathy is effective at treating illnesses that are not
       self-limiting.
       I’d hope this would take the form of a well designed and
       appropriately controlled blinded clinical study (but from your
       suggestion that homeopathy requires a ‘different type of research’
       I doubt this would be the case.)
   83. #83 Mark James
       Newcastle
       March 25, 2013
       I’ve really enjoyed reading the debate between Krebiozen and Leigh
       Jackson. But do feel that there is a lot more to placebos than a
       subjective response of feeling better. Placebos cannot cure cancer,
       diabetes, cardiovascular disease etc. But they can improve pain
       perceptions. Specifically in sport and exercise.
       A reliable study by Beedie et al., demonstrated that although
       caffeine does improve performance, the expectations specifically
       influence how well you will do
       http://europepmc.org/abstract/MED/18091009
       McClung & Collins show that there are little differences between a
       supplement compared to a positive expectancy.
       http://europepmc.org/abstract/MED/17876973
       There are many more in the sport and exercise field where a placebo
       can improve an athletes performance. If the person can run faster
       does that not mean the placebo has worked?
   84. #84 MI Dawn
       March 25, 2013
       @Science Mom: yeah, I know. But since she’s so fond of the title
       (and maybe can use it legally where she is?) I thought I’d go ahead
       and call her by it. If she practiced in the US, I wouldn’t.
   85. #85 Grant
       March 25, 2013
       Good reminder re her degree – I once took her to task with it on my
       blog, checking out what she had and whatnot. I can’t edit my
       earlier post, but strike the ‘Dr.’ portion.
   86. #86 Mephistopheles O'Brien
       March 25, 2013
       Mark James – perhaps you’ve seen the Disney movie “Dumbo”. Did the
       magic feather work?
   87. #87 Krebiozen
       March 26, 2013
       Mark James,

     If the person can run faster does that not mean the placebo has
     worked?
       It depends on what you mean by “worked”. I’m certainly not denying
       that placebos can have subjective psychological effects. Nor would
       I deny that those subjective psychological effects can affect a
       person’s neurochemistry, physiology or behavior, including sports
       performance, but so can a pep talk from a coach, being chased by a
       hungry predator and a million other things.
       I think the mechanism behind these effects is interesting, but I’m
       not convinced think they are clinically useful or ethical on their
       own, in the form of a sugar pill or a saline injection, for
       example. I also think it is worth maximizing these effects when a
       patient is given an active treatment as Orac suggested in the OP.
       Hypnotherapy is essentially a way of harnessing this element of the
       ragbag of things that are collectively referred to as “the placebo
       effect”, but without the need to deceive the patient. So are
       therapies like counseling, massage, yoga or taking a walk in the
       sunshine.
       BTW, the first study you linked to is a good example of the
       confusing results we see in this area; giving caffeine to cyclists
       improved performance, but more so when the cyclists were told they
       had not been given it? The effect size of being told they had been
       given caffeine when they had not was very small 0.7%, which isn’t
       very impressive. I wonder if this is just noise, or perhaps poor
       blinding.
       I don’t have access to the full text of the second study, so I
       can’t see how big the effect sizes were, but it would be
       interesting to know, though what the study really shows is that the
       ‘performance enhancing’ supplements they were testing had no effect
       above placebo. It would be interesting to compare the effects of a
       placebo with the effects of superstitious amulets like a pair of
       lucky socks, visualization, a pep talk etc. etc.. I strongly
       suspect the exact same phenomenon is involved.
   88. #88 (Long) Weekend Reading | Science-Based Pharmacy
       March 29, 2013
       [...] The “myth” of placebo effects [...]
   89. #89 Antilusional
       April 12, 2013
       “Dr” (cough) Nancy Maliquack isn’t being disclosing her cherry
       picking.
   90. #90 KR
       TN
       May 14, 2013
       Ughh, I loathe Heidi Stevenson. Her articles drive me bonkers. And
       whenever anyone brings up the obvious holes and omissions in her
       research about anything she blindly points her finger at people and
       accusing them of “fear mongering”. If you happen to best her or
       bring up an irrefutable point she will delete your comment and
       attack your rhetoric saying it doesn’t follow [her] rules of
       “debate”.
       People who are so one sided and biased about important issues
       should not be allowed to inform the public at large and present
       their ideas as the only true scientific “fact”. Impressionable
       people listen to this garbage, find a few emotional choice phrases
       to cling to and then use them in every subsequent argument as the
       be-all-end-all when the truth is: the surface has to be tapped.

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   [3016012-poster-1280-pillss.jpg] [fastcoexist-dark-txt.svg] Co.Exist

   2013-08-26

   Co.Exist

The Placebo Effect Is Real. Now Doctors Just Have To Work Out How To Use It

   A growing body of research shows that treatments ranging from sugar
   pills to the "ritual of medicine" really do improve patient health.
   Doctors could start to harness the placebo's power by making small
   changes.

   In the last decade, the study of placebo has moved from the backwaters
   of medical research to nearer the mainstream. There is now a Program in
   Placebo Studies at Harvard. NIH and nonprofits like the Robert Wood
   Johnson Foundation fund placebo work. Journals publish papers. What
   used to be dismissed is now taken increasingly seriously.

   It's fair to say this shift wouldn't have happened without Ted
   Kaptchuk, who heads Harvard's placebo program. Over 35 years, he's been
   investigating placebos, which are medical interventions without active
   drug ingredients, in various contexts and expanding the scope of the
   field--including, for a time, to his own acupuncture practice.
   "The placebo effect is brought about by much more than sugar pills and
   saline injections. It's about the whole "drama" or "theater" of
   medicine.
   "

   To Kaptchuk, the placebo effect is brought about by much more than
   sugar pills and saline injections. It's about the whole "drama" or
   "theater" of medicine--essentially the context of the encounter between
   patient and physician--as much as treatment itself. "The placebo effect
   is the effect of everything surrounding the fake pill, or the real
   pill," he says. "It's the compassion, trust, and care. It's the ritual
   and symbols. It's the doctor-patient interaction."

   Kaptchuk has published several papers that have gotten wider attention
   beyond the world of academic journals and conferences. For example, he
   got a big response for a study with irritable bowel syndrome patients,
   where he showed that placebo could be effective even when patients knew
   the treatment was fake. (The drug bottle had a big "placebo" label on
   it.) Though the study only included 80 volunteers, the results seemed
   to indicate something profound: When patients want to get better, and
   believe that doctors are there to help them, good things happen.

   Kaptchuk credits the growing respectability of studying placebos down
   to the wider availability of neuro-imaging techniques. By demonstrating
   physiological impact in the brain when a patient takes a placebo
   treatment, researchers can move beyond conjecture about how the effect
   works. "The discovery of neurobiology has made physicians in the
   medical community more comfortable that something is going on that they
   have to pay attention to," he says. "Before it was just the
   imagination. Now, the imagination has a real neurobiology."

   Researchers can begin to see inside the brain, helping to gauge what
   works and when. Neuro-imaging has allowed researchers to look at
   whether there's a genetic basis for why some people seem more
   susceptible to placebo treatments than others.

   The recent research findings do beg a serious question, though. Are we
   going to see actual treatments based on pills that are no more than
   sugar as alternatives to active drugs? How might medicine incorporate
   the work that Kaptchuk and other placebo researchers are bringing to
   the world?

   In some ways, it's already happening. A survey from the U.K., recently
   showed that many doctors are already prescribing placebos on a regular
   basis. Out of 783 doctors, 12% said they had used "pure" placebo (sugar
   pills, saline injections) while 97% had used "impure placebos"
   (prescribing drugs without scientific basis, like antibiotics for
   viruses). More than three-quarters said they did so at least once a
   week, and many didn't have an ethical problem with deceiving patients
   if treatments were effective.

   Kaptchuk is not in favor of deception. Nor does he think sugar pills
   cure cancer. He does believe placebo research can help with conditions
   where self-appraisal is important. "You can change a person's sense of
   the symptoms. The only thing we know for sure is that the ritual of
   medicine changes subjective outcomes and that there's a biological
   substrate to that," he says. "The placebo is going to be for things
   like headache and back pain, muscular skeletal pain, and digestive and
   urinary problems."

   Kaptchuk says small changes in how drugs are delivered can improve a
   patient's well-being. For example, if you inject someone with morphine,
   and tell them what they're getting, it has double the effect of putting
   an IV in their arm and telling them nothing. That puts more
   responsibility on the medical community to provide care, rather than
   just relying on drugs to do the work.

   "Placebo is about how we improve care independent of medication. It
   really puts the onus on the physician, because it says, 'if you're not
   doing this, it's actually bad care.' In the pharmaco-centric world that
   medicine is, it's about finding the right drug. Placebo research begins
   to shift that whole concept."

   [Image: Pills via Shutterstock]
   [2328079-photo-schiller.jpg]

Ben Schiller

   Ben Schiller is a New York-based staff writer for Co.Exist, and also
   contributes to the FT and Yale e360. He used to edit a European
   management magazine, and worked as a reporter in San Francisco, Prague
   and Brussels Continued
   August 26, 2013 | 9:15 AM

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   This PatientPlus article is written for healthcare professionals so the
   language may be more technical than the condition leaflets. You may
   find the abbreviations list helpful.
   This page has been archived. It has not been updated since 22/06/2011.
   External links and references may no longer work.

   The placebo effect is a poorly understood phenomenon but recent work
   suggests that placebo represents the psychosocial aspect of every
   treatment and "the study of placebo is essentially the study of
   psychosocial context that surrounds the patient".^[1]
   Research in the field of neurobiology suggests that a person's
   expectation of an effect generates activity in certain areas of the
   brain. Brain regions identified as having activity after administration
   of a placebo include the anterior cingulate cortex, dorsolateral
   prefrontal cortex and basal ganglia.^[2]
   The placebo effect needs to be taken into account in clinical trials:
     * It has been reported to affect quality-of-life assessments.^[3]
     * In certain settings placebo interventions can influence
       patient-reported outcomes, especially pain and nausea, although it
       is difficult to distinguish patient-reported effects of placebo
       from biased reporting. Variations in the effect of placebo were
       partly explained by variations in how trials were conducted and how
       patients were informed.^[4]

   It is important therefore to differentiate between the placebo effect
   exhibited in clinical trials (which needs to be minimised) and that
   seen in clinical practice (which should be maximised).^[5] The
   difference between a perceived placebo effect and a true placebo effect
   should be recognised.

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Perceived placebo effect

   This is seen in the placebo arm of a clinical trial, eg new
   antihypertensive drugs may drop the average blood pressure by 5 mm Hg,
   but this may not be true placebo effect as other factors may confound
   the situation. Such factors include:
     * The natural course of the disease - blood pressure may normally
       reduce over time, thus exaggerating the placebo effect.
     * Regression towards the mean - biological variables often
       fluctuate.^[6] When first measured they are probably approaching
       their maximum and so further measurements are likely to show a
       reduction.
     * Increased skill of the investigator - this may alter measurements
       up or down as more measurements are made.
     * Variable factors within the same patient - white coat hypertension
       may reduce as patients become accustomed to having their blood
       pressure measured, which would increase the apparent placebo
       effect.
     * Non-apparent simultaneous changes - on entering the trial, the
       patient may change their behaviour, on purpose or otherwise, in
       such as way as to confound the outcome, eg eat less salt, take more
       exercise.

True placebo effect

   This can only be studied if an untreated group is included along with
   active and placebo treated groups. These are relatively uncommon but it
   has been discovered that:
     * Placebo treatment is more effective in relieving pain compared with
       no treatment. To achieve this, patients need to be conscious
       (placebo was given to sleeping patients and no difference noted).
     * Physical placebos, eg invasive techniques such as injection, are
       more powerful than simple oral placebos.^[7]
     * Topical placebo is also more effective than oral placebo, eg in
       primary varicose veins.
     * There is no standard degree of placebo effect (approximately 30% is
       often given) and its extent depends upon numerous factors
       including:
          + The demeanour of the person offering treatment.
          + The patient's attitude to health and their feelings about the
            treatment and person offering it.
          + The suggestibility of the patient.
          + The form of treatment, eg whether it has worked before, how
            expensive it is, its invasiveness and the reasons given as to
            how it works.
     * Placebo effects on pain are generally greater than on other
       symptoms.
     * Placebo effects are not always useful and may produce adverse
       effects (nocebo effects).
     * Variations in placebo remission and response rates reported in
       randomised controlled trials can be significantly influenced by the
       country in which the trial is conducted.^[8]
     * A study of osteoarthritis patients elicited that the placebo effect
       was effective in reducing pain and stiffness and improving
       function.The pain-relieving effect increased when the active
       treatment effect, baseline pain and sample size increased and when
       placebo was given through injections/needles.^[9]
     * One study found no difference in placebo effect whether the patient
       was suffering from functional or organic gastrointestinal
       disease.^[10]
     * A study of migraine patients found that placebos were more
       effective in treating acute headache than in prophylaxis.^[11]

   Provide Feedback

Further reading & references

    1. Koshi EB, Short CA; Placebo theory and its implications for
       research and clinical practice: a review Pain Pract. 2007
       Mar;7(1):4-20.
    2. Oken BS; Placebo effects: clinical aspects and neurobiology. Brain.
       2008 Nov;131(Pt 11):2812-23. Epub 2008 Jun 21.
    3. Eickhoff JC; Placebo effect-adjusted assessment of quality of life
       in placebo-controlled clinical trials. Stat Med. 2008 Apr
       30;27(9):1387-402.
    4. Hrobjartsson A, Gotzsche PC; Placebo interventions for all clinical
       conditions. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD003974.
    5. Ernst E; Placebo: new insights into an old enigma. Drug Discov
       Today. 2007 May;12(9-10):413-8. Epub 2007 Apr 2.
    6. Asmar R, Safar M, Queneau P; Evaluation of the placebo effect and
       reproducibility of blood pressure measurement in hypertension. Am J
       Hypertens. 2001 Jun;14(6 Pt 1):546-52.
    7. Diener HC; Placebo effects in treating migraine and other
       headaches. Curr Opin Investig Drugs. 2010 Jul;11(7):735-9.
    8. Garud S, Brown A, Cheifetz A, et al; Meta-analysis of the placebo
       response in ulcerative colitis. Dig Dis Sci. 2008 Apr;53(4):875-91.
       Epub 2007 Oct 13.
    9. Zhang W, Robertson J, Jones AC, et al; The placebo effect and its
       determinants in osteoarthritis: meta-analysis of randomised
       controlled trials. Ann Rheum Dis. 2008 Dec;67(12):1716-23. Epub
       2008 Jun 9.
   10. Musial F, Klosterhalfen S, Enck P; Placebo responses in patients
       with gastrointestinal disorders. World J Gastroenterol. 2007 Jul
       7;13(25):3425-9.
   11. Diener HC, Schorn CF, Bingel U, et al; The importance of placebo in
       headache research. Cephalalgia. 2008 Oct;28(10):1003-11. Epub 2008
       Aug 22.

   Disclaimer: This article is for information only and should not be used
   for the diagnosis or treatment of medical conditions. EMIS has used all
   reasonable care in compiling the information but make no warranty as to
   its accuracy. Consult a doctor or other health care professional for
   diagnosis and treatment of medical conditions. For details see our
   conditions.
   Original Author: Dr Laurence Knott Current Version: Dr Hayley Willacy
   Last Checked: 22/06/2011           Document ID: 2857  Version: 22     © EMIS

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   Home  >  Research  >  Experiments  >  Placebo Effect

Placebo Effect

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   Explorable.com
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   <a href="http://explorable.com/placebo-effect">Pla
   __________________________________________________

   A placebo effect is a phenomenon which may result in some therapeutic
   effect in subjects given placebo.

Experimental Research

     * 1Experimental Research
     * 2Research Variables
          + 2.1Independent Variable
          + 2.2Dependent Variable
          + 2.3Controlled Variables
          + 2.4Third Variable
     * 3Cause and Effect
          + 3.1Control Group
          + 3.2Research Bias
          + 3.3Social Science Subjects
               o 3.3.1Placebo Effect
               o 3.3.2Double Blind Method
     * 4Conducting an Experiment
          + 4.1Randomized Controlled Trials
          + 4.2Pretest-Posttest
          + 4.3Solomon Four Group
          + 4.4Between Subjects
          + 4.5Within Subject
          + 4.6Repeated Measures
          + 4.7Counterbalanced Measures
          + 4.8Matched Subjects

   [3.3.1 Placebo Effect____________]
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   A placebo is a sham medical intervention that exploits the
   hope/expectancy-effect to the treatment. It involves giving subject an
   inert sugar pill, and he/she is told that it may improve the condition,
   but the person is completely unaware of the fact that it is inert.

   In medicine, it has been observed that patient’s belief does indeed
   sometimes result in therapeutic effect and cause patient’s condition to
   improve.

   Placebo treatment is widely practices in medicine, and it has been
   recognized to have clinically important effects. A placebo has been
   defined as a substance or any procedure that is given objectively
   without any specific activity for the condition being treated.

   Indeed, wide variety of things can be considered placebo and do show
   placebo effect. These may include pharmacological substances like
   pills, inhalants, creams, injections or even medical devices such as
   ultrasound, surgery, acupuncture to name few.

   In one study, it was observed that patient recovery can be enhanced
   with positive suggestions and comments by the physician like

     “you will certainly be better in few days with this treatment”

   and if the patient is given negative words like

     “I am not sure that this treatment can work for you”

   it negatively affect the recovery of patient.

How it Works?

   The placebo effect phenomenon is related to the perception and
   expectations of the subject. If subject see it helpful, it can heal,
   and if viewed as harmful, it can cause negative effects or what is
   known as nocebo effect.

   Both expectations and conditioning play an important role in placebo
   effect and make different kind of contribution.

   The expectancy effect is seen to be enhanced through factors like
   positive attitude of doctor, different in color and size of placebo
   pills, or use of injections. In one study, researchers found that
   response to placebo treatment was increased from 44% to 62% when the
   healthcare professional gave them warmth, attention, and confidence.

   Conditioning on the other hand exerts long lasting effects and it seems
   to affect early stages of information processing. However, as placebo
   effect is based upon conditioning and expectations of the subject, the
   effect is seen to disappear if the subject is informed that his/her
   expectations are unrealistic, or that placebo treatment is completely
   ineffective.

   Despite ongoing controversy concerning use of placebo therapy, there
   are number of reports showing positive effects of placebo treatment.
   Placebo seems to work in alleviating pain, anxiety, depression,
   Parkinson’s disease, arthritis, and even cancer.

   Remarkable recovery of “Mr. Wright” from a deadly cancer is just an
   example of placebo treatment. Placebo effects seems not only be arise
   from conscious belief but also from subconscious associations between
   recovery and treatment as researchers has found that placebo effect
   does arise from active processes in brain.
   « Previous
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The Anti-Placebo Effect

   39 Post author: ShannonFriedman 28 September 2013 05:44AM

   Just about everyone is familiar with the placebo effect at this point.
    What I've discovered through my personal studies working with people
   suffering from anxiety and depression is that there is actually a
   significant related effect, which I have dubbed the anti-placebo
   effect.

   Google says: pla·ce·bo ef·fect

   noun

   1.
   a beneficial effect, produced by a placebo drug or treatment, that
   cannot be attributed to the properties of the placebo itself, and must
   therefore be due to the patient's belief in that treatment.

   I say: anti·pla·ce·bo ef·fect

   noun

   1.
    1. a beneficial effect, produced by a treatment, that is not
       attributed to treatment itself or has stopped being noticed, and
       thus the patient does not believe in that treatment as effective.

   Its easy to miss treatment working.  For example, as a kid grows up,
   its easy to miss how their vocabulary is growing, but for someone who
   doesn't seem them every day, it may be immediately obvious "my how
   they're talking more!"  In other words, an anti-placebo effect is what
   happens when someone is having an intervention that is causing their
   life to improve, but the person does not believe that they are
   improving.

   This effect is most common with people who suffer from depression, who
   have biases for sad [1] and otherwise negative stimuli compared to the
   general population, and is also true of people suffering from anxiety
   from my personal client tracking.  Its also important to note that this
   bias persists after the recovery of the depressive episode.

   The reason that this is important is that those recovering from anxiety
   and depression have a tendency to believe that they are not doing as
   well as they are - due to this cognitive bias creating an anti-placebo
   effect for them, which results in their giving up too soon on
   interventions which are effective and thus not getting better and
   regressing to old unpleasant patterns.

   It has been interesting since tracking results of my own clients [2] -
   I have all of them track scores at the beginning of their sessions on
   the site moodscope.com at the beginning of their sessions, so that we
   can see their progress over time with a consistent bias of the time of
   tracking being start of session (as opposed to other random biases such
   as wanting to take the quiz when in an especially good or bad mood).  I
   also take extensive notes and track other metrics of progress.

   What I've found, is that many clients hit a point after a few weeks or
   months, where they are questioning if they have made any progress.
   Because I take metrics to prepare for this, I am able to point my
   clients at their metrics, and say for example, that according to their
   self reports, their mood has increased by 50% and their productivity
   has doubled.  What typically happens when I review score + notes with
   the client in question is that once they look back at how things were
   before compared to how they are now, they realize that they actually
   have made progress, and this is often followed with additional forward
   progress.

   It is interesting to put this in perspective with the hedonic treadmill
   [3].  The hedonic treadmill is the supposed tendency of humans to
   quickly return to a relatively stable level of happiness despite major
   positive or negative events or life changes.  What I'm finding with my
   studies is that it is often true for people recovering from depression
   when they take an overall evaluation (go meta), especially from a low
   point, but that when they look back at the factors that have changed,
   and they take the mood score test looking at different aspects of their
   experience on moodscope.com, they actually do have a more positive life
   experience when measured this way.  When I point out the inconsistency,
   people generally determine that the moodscope.com reported experience
   is more accurate (especially when supplemented by going over session
   notes) and over time, most clients do get off the hedonic treadmill and
   proceed to having the meta level catch up with moodscope.com.

   The good news about this for people suffering from anxiety and
   depression at large:  If you are aware of the negative cognitive bias
   and anti-placebo effect, you can take steps to account for and correct
   this bias.  One of the best ways to do this is by taking metrics along
   with notes that you can look at later.  When you look back, look at
   what your overall trend is, and try to focus on that more than if you
   happened to have a bad day or week.  If you have been progressing with
   a good linear regression, odds are that if you don't give up the new
   better patterns and habits you have created, they will continue to
   serve you. Although external factors to the one variable you are
   studying do complicate this and need to be taken into account.


   [1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2847035/

   [2] http://www.depressiontoproductivity.com/your-clients-really-improve
   /

   [3] http://en.wikipedia.org/wiki/Hedonic_treadmill


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   Comment author: TheOtherDave 28 September 2013 04:09:13PM *  28 points
   [+] (3 children)
   Comment author: TheOtherDave 28 September 2013 04:09:13PM *  28 points
   [-]

   The thing that made this most obvious to me was training my dog.

   For example, when conditioning her out of a behavior I dislike, my
   intuitive approach seems to be to monitor the intensity of the
   behavior... I expect a steady stream of intense performances
   BBBBBBBBBBBBBBBBBBBB
   to become a stream of less-intense performances
   bbbbbbbbbbbbbbbbbbbb
   and then disappear altogether.

   But in reality the intensity doesn't change much, and sometimes it even
   gets worse. I never get "bbb..." What declines is the frequency. That
   is,
   BBBBBBBBBBBBBBBBBBBB
   becomes
   BBBBBB_BBBBBBBBB_BBB
   which, from my intuitive perspective, is essentially no progress at
   all... I don't notice.

   And then on the other end, when the behavior is almost extinguished, I
   get
   _____B___B_______B___
   which, from my perspective, is an endless series of "oh good, we got
   rid of this behavior -- oh, crap, now it's back again, just as bad as
   it ever was! This isn't working!"

   So it really really helped to keep a chart of the frequency of the
   behavior that I can look back at and realize that actually, we've been
   making steady progress all along, even though it completely doesn't
   feel like progress at all.

   After my stroke, when I was relearning to walk/talk/think, that
   strategy was absolutely critical to warding off despair. I charted
   everything, and it made a huge difference.
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   Comment author: hyporational 29 September 2013 10:19:12AM 4 points [+]
   (2 children)
   Comment author: hyporational 29 September 2013 10:19:12AM 4 points [-]

   After your stroke, what kinds of things did you chart specifically? In
   which areas was the progress most motivating?
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   Comment author: TheOtherDave 29 September 2013 03:33:08PM 9 points [+]
   (0 children)
   Comment author: TheOtherDave 29 September 2013 03:33:08PM 9 points [-]

   Some examples:
   How many times I could raise and lower my leg before being exhausted.
   Number of steps I could take at a time.
   Words I blocked on.
   Number of times I became altogether unable to complete a sentence.
   (Though this was more approximate.)
   Number of pushups I could do.
   Distance I could walk.
   Complexity of the hardest logic-puzzle I'd successfully solved.
   How many words I could write before my hand was exhausted.
   How coherently I could write (I still have somewhere a piece of paper
   on which I wrote the same sentence, over and over, on each line; it
   gradually morphs from a literally indecipherable scrawl to something
   indistinguishable from a normal-though-sloppy person's handwriting.)

   These were, of course, at different times in my recovery.
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   Comment author: TheOtherDave 29 September 2013 04:01:46PM 6 points [+]
   (0 children)
   Comment author: TheOtherDave 29 September 2013 04:01:46PM 6 points [-]

   Oh, and re: motivating... that's a much more difficult question to
   answer.

   The charting techniques were "motivating" only in a prophylactic
   sense... they helped me resist a certain kind of "I'm not getting any
   better" despair that was otherwise very compelling and very
   demotivating.

   Positive motivation to progress was much harder to come by, and I had a
   much less concrete grasp on it. I was often in a not quite apathetic,
   but highly disengaged state with respect to my recovery. Mostly I dealt
   with this by accepting it as just another intermittent deficit where I
   had to ride out the bad periods and take advantage of the good ones.

   I think the closest I can come to describing it accurately is to say
   that motivation-to-progress was highly correlated with focus; when what
   I was doing was recovery, I was very motivated to make progress. What
   direction causality ran, though, I have no idea.
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   Comment author: pjeby 30 September 2013 10:06:46PM 7 points [+] (3
   children)
   Comment author: pjeby 30 September 2013 10:06:46PM 7 points [-]

   A related concept: "change amnesia". Our general memory of our past
   behaviors is heavily influenced by our expected present behaviors, such
   that we tend not to remember how we behaved differently in the past,
   and have difficulty believing we were ever that dumb/lame/whatever when
   actually confronted with evidence (such as pictures, journal entries,
   etc.)

   Some people have this worse than others: a couple times I've had
   clients who came to me with a large stack of personal problems, and
   three months later don't know why they're paying me because they're not
   getting any changes... and then when I ask about the problems they had
   when they started, they usually remember telling me about those
   problems, but don't remember having the problems any more. (As in, they
   don't remember experiencing the problem, and don't think that they
   would be the kind of person who would've had a problem like that!)

   For me personally, I have a lot of trouble reconstructing how I thought
   about a subject, once I've self-modified on that topic, with the effect
   usually setting in after a few hours or overnight. (Although honestly,
   I've never tried such a reconstruction any sooner; the difficulty might
   set in within minutes for all I know.) So I can remember that I used to
   think in some messed-up way, and maybe even what behaviors resulted
   from that messed-up thinking, but actually simulating the previous mode
   of thinking becomes difficult and unnatural.
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   Comment author: hyporational 01 October 2013 03:27:50PM *  1 point [+]
   (2 children)
   Comment author: hyporational 01 October 2013 03:27:50PM *  1 point [-]

   The few times I tried, I had to quit journaling out of pure
   embarrassment. After a few months, pretty much the only reaction I had
   reading old entries was: "who the hell is this idiot?"

   My past self was completely alien to me, and I couldn't even understand
   what the words meant. I didn't really write for comprehension, as I
   thought my future self would totally understand me.
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   Comment author: Kawoomba 01 October 2013 03:52:31PM 4 points [+] (1
   child)
   Comment author: Kawoomba 01 October 2013 03:52:31PM 4 points [-]

   Makes you wonder how crucial that whole value-preservation thing
   actually is ...
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   Comment author: hyporational 01 October 2013 04:13:05PM *  0 points [+]
   (0 children)
   Comment author: hyporational 01 October 2013 04:13:05PM *  0 points [-]

   Hehe, a good point. I don't have such a strong reaction reading old
   forum posts for example, though. At least I can understand them, even
   if I don't agree with them.
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   Comment author: Shield 28 September 2013 11:22:18AM 6 points [+] (8
   children)
   Comment author: Shield 28 September 2013 11:22:18AM 6 points [-]

   Are you sure that "anti placebo effect" is a good name though? The
   placebo effect refers exclusively to medical treatment if I'm not
   entirely mistaken, and this seems to have much broader implications in
   basically any sort of training. It's still basically the same effect if
   someone refuses to notice the progress they made with say tutoring, but
   it has nothing to do with medicine or treatment.

   Seems a bit misleading.
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   Comment author: timtyler 29 September 2013 08:59:16AM *  4 points [+]
   (0 children)
   Comment author: timtyler 29 September 2013 08:59:16AM *  4 points [-]

     Are you sure that "anti placebo effect" is a good name though?

   It may be that nocebo has a better claim to being an "anti-placebo
   effect".
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   Comment author: Vaniver 28 September 2013 05:26:59PM *  3 points [+] (0
   children)
   Comment author: Vaniver 28 September 2013 05:26:59PM *  3 points [-]

     The placebo effect refers exclusively to medical treatment if I'm
     not entirely mistaken, and this seems to have much broader
     implications in basically any sort of training.

   While the placebo effect is generally defined in a medical context,
   people rarely throw type errors when you talk about placebos outside of
   medicine. The Hawthorne Effect is the name that productivity boosts due
   to observation / novelty / active treatment go by, but it's seen as
   similar to if not the same as the placebo effect.
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   Comment author: Desrtopa 29 September 2013 04:27:37PM 1 point [+] (0
   children)
   Comment author: Desrtopa 29 September 2013 04:27:37PM 1 point [-]

   I can affirm that I expected the term to refer to something different,
   namely an effect that causes people to do worse based on their concerns
   surrounding an intervention, such as in this study on intercessory
   prayer, where the individuals who knew they were being prayed for did
   worse than the other groups, possibly because they were concerned that
   they were so badly off that they needed people to pray for them.
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   Comment author: Lethalmud 30 September 2013 12:33:17PM 0 points [+] (0
   children)
   Comment author: Lethalmud 30 September 2013 12:33:17PM 0 points [-]

   Maybe Nocebo?

   http://en.wikipedia.org/wiki/Nocebo
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   Comment author: ShannonFriedman 30 September 2013 06:37:53AM 0 points
   [+] (0 children)
   Comment author: ShannonFriedman 30 September 2013 06:37:53AM 0 points
   [-]

   Here's my answer to that:
   http://lesswrong.com/lw/iqr/theantiplaceboeffect/9tiw
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   Comment author: Zaine 29 September 2013 02:04:31PM 0 points [+] (2
   children)
   Comment author: Zaine 29 September 2013 02:04:31PM 0 points [-]

   In the placebo effect, you try something, see results, and believe
   those results derived from what you tried, when in fact what you tried
   could not possibly have had any effect whatsoever; the observed results
   are then attributed to one's beliefs that the tried thing had the
   capacity for effecting change.

   The above refers to a different phenomenon: one tries something,
   doesn't see results, and believes what they tried had no effect, when
   in fact what they tried did have results.

   In the placebo effect, one's beliefs effect change. In the phenomenon
   Shannon refers to, change occurs regardless of one's beliefs.

   Interestingly, when I presented the above description of the placebo
   effect to someone and asked for what they would expect of the opposite,
   they replied, "Change happens and they don't believe it." I would think
   the term, "Opposite-Placebo Effect" or "Opposite of the Placebo Effect"
   a better descriptor, as 'anti-' implies simple negation rather than a
   flipping of observed effects.

   This could of course just be an issue of differing perspectives on what
   is or isn't an intuitive moniker.
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   Comment author: kalium 29 September 2013 08:44:54PM 4 points [+] (1
   child)
   Comment author: kalium 29 September 2013 08:44:54PM 4 points [-]

   Actually the placebo effect is a statistical term covering the entire
   improvement seen in the placebo branch of a trial. Part of the effect
   comes from beliefs, yes. But there are other causes. For instance,
   people tend to enroll in clinical trials when their health is at a
   local minimum, and reversion to the mean can account for a good chunk
   of their improvement.
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   Comment author: Zaine 30 September 2013 05:06:03PM *  0 points [+] (0
   children)
   Comment author: Zaine 30 September 2013 05:06:03PM *  0 points [-]

   I didn't know this, and if there are other instances, would like to
   know all of them. Thank you!
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   Comment author: Viliam_Bur 28 September 2013 07:24:31AM *  4 points [+]
   (2 children)
   Comment author: Viliam_Bur 28 September 2013 07:24:31AM *  4 points [-]

   I have noticed this kind of effect on myself -- I start doing
   something... the improvement is very slow... I convince myself that the
   improvement is zero... so I stop doing it... so I never finish it...
   which I take as a proof that my improvement was zero.

   Having unrealistic expectations makes it even worse, because the higher
   expectation the more disappointment with slow progress.

   Probably the correct solution would be: just record your improvements.
   I imagine something like beeminder, just without the deadlines: create
   a graph for something, enter data points, see the visualization,
   celebrate when you reach some goal.
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   Comment author: 4hodmt 28 September 2013 07:46:20AM 11 points [+] (1
   child)
   Comment author: 4hodmt 28 September 2013 07:46:20AM 11 points [-]

   Beeminder without the deadlines is Beeminder with the weekly rate set
   to zero.
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   Comment author: army1987 28 September 2013 10:41:05PM 2 points [+] (0
   children)
   Comment author: army1987 28 September 2013 10:41:05PM 2 points [-]

   Or even just a text file and a gnuplot script, for that matter.
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   Comment author: hyporational 28 September 2013 06:12:56AM *  4 points
   [+] (3 children)
   Comment author: hyporational 28 September 2013 06:12:56AM *  4 points
   [-]

   I've had personal experience with this phenomenom, but never associated
   it with the hedonic treadmill.

   I think this has also something to do with you current emotional state
   determining which episodic memories you recall. When you feel good, you
   remember all the good stuff, when you feel bad, all the bad things pile
   up. I've found it's really difficult to remember what it was like being
   depressed when I'm well. That has lead to stupidly quitting medication
   a couple of times. Is there a name for this effect?

   EDIT: In my case the improvement with medication was dramatic, so it
   wasn't just a case of not noticing slow progress. My point was the
   anti-placebo effect probably consists of many different kinds of known
   cognitive failure modes, and it might be helpful to recognize them. In
   the problem that I describe, the difficulty is in retrieving memories
   that don't fit the emotional context. The hedonic treadmill effect is
   another type of an effect that fits the category.
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   Comment author: ShannonFriedman 28 September 2013 08:22:44PM *  2
   points [+] (2 children)
   Comment author: ShannonFriedman 28 September 2013 08:22:44PM *  2
   points [-]

   What you're describing sounds like the results from the anti-placebo
   effect, although I didn't go so far as naming that. Basically, you
   don't realize its working (anti-placebo effect), and then you stop and
   regress (what you're pointing to). Since you've figured this out, you
   should have a much easier time avoiding it with the next intervention
   you try, especially if you track the metrics you're most interested in
   seeing changes in.

   One place that things get tricky is that your negative reinforcement
   loops can get started while you're still tracking metrics - as an
   example, perhaps you're doing great, and then you have one bad day, and
   then you make the false assumption that the bad day means that you will
   continue having bad days and that none of the other progress is real.
   If you adopt that belief, then even your mood tracking will decline, so
   its important to be reality checking as much as possible along the way,
   and to remind yourself that one bad day is not as big a deal as weeks
   of good days, and that will help you stay on track. Here's a video of
   me role playing the two attitudes that might be helpful.

   Not quite on topic, but same principle - replace getting the work task
   done with having succeeded in improving on the metric you've been
   tracking for several consecutive weeks, and imagine how the optimistic
   person would respond to a down day, with that attitude, v.s. the
   overwhelmed/depressed role play person.
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   Comment author: hyporational 29 September 2013 09:58:01AM *  0 points
   [+] (1 child)
   Comment author: hyporational 29 September 2013 09:58:01AM *  0 points
   [-]

   Edited the original to clarify. The video link didn't work, it's here,
   pretty descriptive of the basic attitudes. Changing attitudes to me
   feels like changing beliefs, you can't simply choose them by tricks of
   imagination. Medication helped with that. These days my problem is more
   simple avolition than depression, any non pharma tips on that? (I'm a
   physician.)

   It would be nice to know how much of imagined SSRI poop out doesn't
   actually happen. Unfortunately there aren't similar tracking tools in
   finnish to give to my patients. Maybe pen and paper should suffice.
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   Comment author: ShannonFriedman 29 September 2013 02:47:57PM 0 points
   [+] (0 children)
   Comment author: ShannonFriedman 29 September 2013 02:47:57PM 0 points
   [-]

   Yes, a lot of it has do to with having the parts of your mind that are
   action oriented not in alignment with the ones that want to have fun.
   If you're in that state for a long time, or in any way that ingrains
   the patterns hard, eventually you get to more extreme states like lack
   of interest in anything.

   I use non-medication techniques to get people out of these states as my
   profession. You might find this audio helpful.
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   Comment author: RolfAndreassen 28 September 2013 06:17:07PM 3 points
   [+] (1 child)
   Comment author: RolfAndreassen 28 September 2013 06:17:07PM 3 points
   [-]

     people suffering from anxiety from my personal client tracking.

   This phrase probably does not carry the intended meaning.
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   Comment author: ShannonFriedman 28 September 2013 08:14:34PM 0 points
   [+] (0 children)
   Comment author: ShannonFriedman 28 September 2013 08:14:34PM 0 points
   [-]

   LOL, indeed :)
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   Comment author: CronoDAS 30 September 2013 07:04:39AM 2 points [+] (0
   children)
   Comment author: CronoDAS 30 September 2013 07:04:39AM 2 points [-]

   I'm reminded of the peak-end heuristic; the times that you're miserable
   are often far more dramatic and available than the times that you're
   not, so when you think of how you've been feeling over a period of
   time, you get a biased result.
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   Comment author: katydee 28 September 2013 08:43:04AM 2 points [+] (0
   children)
   Comment author: katydee 28 September 2013 08:43:04AM 2 points [-]

   Very interesting post. I'd like to hear more about what sorts of
   situations tend to produce these effects, as it sounds like information
   that could potentially be quite valuable.
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   Comment author: EvelynM 30 September 2013 02:28:55AM 1 point [+] (1
   child)
   Comment author: EvelynM 30 September 2013 02:28:55AM 1 point [-]

   This effect isn't limited to people with anxiety and depression. People
   losing weight also experience it:
   http://www.3fatchicks.com/forum/metabolic-research-center/146593-paper-
   towel-theory.html

   It's hard to be objective about yourself. Using tools to gain
   objectivity is a good thing.

   I agree anti-placebo isn't a a good name. It's more like a distorted or
   cloudy mirror (don't see yourself clearly). but that doesn't capture
   the difficulty of remembering precisely how you were a long time
   before, to capture changes that happen at a slow rate.

   Having a good name for this, will help people to pass along the idea.
   Thanks Shannon.
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   Comment author: ShannonFriedman 30 September 2013 04:19:39AM *  2
   points [+] (0 children)
   Comment author: ShannonFriedman 30 September 2013 04:19:39AM *  2
   points [-]

   The way that I came up with the name, was that someone was suggesting
   that my taking metrics might create a placebo effect, where people
   would believe that they were doing better than they actually were.

   So, my response to this was that I was not trying to create a placebo
   effect, but rather, to avoid a placebo effect in the opposite
   direction.

   So while I agree with you that this effect is not an opposite (why I
   referred to it as related instead of reverse), I do think that it is
   the opposite of what a lot of people fear - that they are experiencing
   a placebo effect.

   In short, people being afraid of having a placebo effect is often how
   this effect comes to be - they don't want to create false hope and then
   have it dissipate, so instead they refuse to believe or acknowledge
   real positive results when they see them.

   So, I would say that the title is reasonable regarding people's
   expectations, but not in the precise using of the term placebo sense.
   Personally, I think that expectations are more important for titling.
   Fewer people will pay attention to a precisely named definition that
   they know nothing about, whereas calling it the anti-placebo effect
   grabs attention - specifically the attention of people who have this
   bias.
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   Comment author: hyporational 29 September 2013 10:28:35AM 1 point [+]
   (1 child)
   Comment author: hyporational 29 September 2013 10:28:35AM 1 point [-]

   I wonder if there are superstimuli for appreciating gradual progression
   that impair our sensitivity to do so. Video games come to mind.
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   Comment author: Viliam_Bur 30 September 2013 08:15:56AM *  4 points [+]
   (0 children)
   Comment author: Viliam_Bur 30 September 2013 08:15:56AM *  4 points [-]

   The whole internet thing -- you click something and you expect to get
   results within seconds.

   Train your expectations with this... and then try to accomplish
   something in real life. Even if it takes days, it feels like eternity.
   If it takes months, it might as well happen after Singularity.
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   Comment author: Dentin 28 September 2013 06:46:30AM 1 point [+] (0
   children)
   Comment author: Dentin 28 September 2013 06:46:30AM 1 point [-]

   (Posting feedback as requested) Shannon - the only real problem I see
   in my sleep-deprived stupor is the very last sentence, which seems out
   of place and partially constructed.
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   Comment author: Decius 11 October 2013 10:08:52AM 0 points [+] (0
   children)
   Comment author: Decius 11 October 2013 10:08:52AM 0 points [-]

   Mindhacking idea: fudge the historical results such that the trend line
   always appears positive, and use that as a primary intervention. This
   requires either violating informed consent (a bad thing) or exercising
   doublethink or another method of self-deception.
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   Comment author: CronoDAS 30 September 2013 07:03:27AM *  0 points [+]
   (0 children)
   Comment author: CronoDAS 30 September 2013 07:03:27AM *  0 points [-]

   When I saw "anti-placebo effect" I thought of this instead...

   Edit: Beaten to it.
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   Comment author: tgb 28 September 2013 03:16:20PM 0 points [+] (1 child)
   Comment author: tgb 28 September 2013 03:16:20PM 0 points [-]

   Dark arts for a good use? Modify the surveys to show them having even
   more progress than they did so they get even more self-confidence.
   Don't worry, they won't notice!
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   Comment author: Dorikka 29 September 2013 04:14:08AM 0 points [+] (0
   children)
   Comment author: Dorikka 29 September 2013 04:14:08AM 0 points [-]

   Except that if one did, things might go very, very badly for you.
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   Comment author: RomeoStevens 28 September 2013 08:38:05AM 0 points [+]
   (1 child)
   Comment author: RomeoStevens 28 September 2013 08:38:05AM 0 points [-]

   I have been supplementing rhodiola rosea and your example is the exact
   thing it promises, a halving of depressive symptoms along with other
   benefits. I'm not sure if it's working.
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   Comment author: ShannonFriedman 28 September 2013 03:23:58PM *  1 point
   [+] (0 children)
   Comment author: ShannonFriedman 28 September 2013 03:23:58PM *  1 point
   [-]

   Yeah, hard to know in retrospect, I would love to hear more about your
   results in as much as you can tell. For future such attempts where
   you're trying something like this, I recommend taking a baseline on a
   mood tracking site for a week or two before starting, if you can manage
   it, and then tracking for at least however long they claim it takes to
   get results. I also recommend just generally taking baselines, maybe
   every couple to few months - that way, even if you don't want to mood
   track all the time, you at least have some reasonable random sampling
   to look back on to see how you're doing over time. When you track, its
   ideal if you find a way to have uniform bias - so always take the test
   at the same time each day for example, or randomize the time if you're
   doing many data points and can handle noise - one problem with mood
   tracking is that people tend to take it when they are feeling
   especially good or especially bad or generally motivated by extreme
   mood, so its good if you can find a way to minimize that particular
   bias.
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   A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

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Placebo (placebo effect)
     __________________________________________________________________

Placebo (placebo effect): A placebo is any substance that is not known to
have any pharmacological effects (produces no meaningful changes in an
oranism, either chemical, biological, etc.) that is made to look like an
active ("real") drug. Sometimes the act of taking a pill produces an effect
if the person believes the pill is active. To compensate for this, scientists
often give placebos to determine if an effect is due to the "real" drug or
from the act of just taking a pill. For additional information, see Control
Condition.


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Understanding and Using the Placebo Effect

Understanding and Using the Placebo Effect

   October 01, 2006 | Addiction, Alcohol Abuse, Amphetamine Related
   Disorders
   By Walter A. Brown, MD

   Most physicians make at least some use of the placebo effect to enhance
   treatments, whether they realize it or not. This article examines the
   extent of the placebo effect in patients with psychiatric illness, and
   reviews what is known about how placebos work. It then discusses the
   application of the placebo response in enhancing the effects of
   treatment modalities in psychiatry.

   It is instructive to note a feature of virtually every antidepressant
   efficacy trial: in outpatients with moderately severe depression whose
   symptoms are assessed using the Hamilton Rating Scale, most of the
   improvement occurs during the first 2 weeks of treatment, and during
   this time, no differences in outcome between active drug and placebo
   are evident. After about 2 weeks, the placebo response reaches a
   plateau. Response to medication may continue to increase for a time,
   but during the period when most of the improvement occurs, placebo and
   medication produce similar responses.

   In fact, the strength of the placebo response can be quite significant
   in several psychiatric disorders.^1 Panic disorder is highly responsive
   to placebo, with a nearly 50% improvement in symptoms among patients
   assigned to that treatment strategy. In patients with posttraumatic
   stress disorder or depression, the placebo response is greater than
   30%, and a response in the 30% range is also seen in generalized
   anxiety disorder.

   Patients with other conditions, including obsessive-compulsive disorder
   (OCD) and psychosis, are less likely to exhibit a placebo response.
   Clearly, the placebo response is not uniformly strong in all
   psychiatric conditions. We have used these findings as a basis for
   recommending that clinical trials of agents being tested in patients
   with psychiatric disorders always include a placebo arm.^1

   Placebo vs pharmacotherapy or psychotherapy

   How do responses to placebo compare with those achieved with
   medication? When treated with clonazepam or an SSRI, 60% to 70% of
   patients with panic disorder become panic-free during a 10-week
   treatment period. During the same period, half or more of patients with
   panic disorder who are treated with placebo become panic-free,
   underscoring the magnitude and importance of the placebo effect in this
   common condition.^2Active drug treatment for depression leads to
   improvement in about 60% to 70% of patients, while placebo
   administration is followed by improvement in 30% to 40%, again an
   impressive contribution.^3

   Conditions that are poorly responsive to psychotherapy are also
   unlikely to respond to placebo. Patients with
   attention-deficit/hyperactivity disorder, for example, are more likely
   to improve with medication than with behavior therapy. We would not
   expect a robust response to placebo in this patient group.

   The results of a collaborative National Institute of Mental Health
   study on the treatment of depression are informative.^4 Most of the
   patients had unipolar disease and were mildly, moderately, or severely
   ill. Some were randomized to clinical management and placebo; they
   attended a clinic, were given a placebo pill, and asked how they were
   doing. Patients in other groups were randomly assigned to
   cognitive-behavioral therapy, interpersonal psychotherapy, or
   imipramine. When the results were analyzed, no differences in outcome
   were evident according to the various treatments. None showed any
   advantage over the others.

   The analysis was also conducted according to whether patients were
   mildly or moderately/severely ill, and there the effects of some of the
   treatments did separate. In the less severely ill patients, no
   statistically significant difference was present among the treatments.
   In the more severely ill patients, imipramine, which was a popular
   antidepressant at the time the study was conducted, had an advantage
   over the 2 psychotherapies and placebo. Although there was a difference
   between the psychotherapies and placebo, it was not statistically
   significant. In the severely ill patients, imipramine worked better
   than any other treatment modality, but placebo was about as good as the
   psychotherapeutic strategies.^4

   Although cognitive therapy for depression is widely used and taught in
   residency programs, the overwhelming majority of studies that have
   compared cognitive therapy with a pill placebo in the treatment of
   moderately severe depression show no difference in efficacy.^5,6 Less
   severely ill patients may benefit from any one of several different
   types of treatment, including psychotherapy, alternative therapies, and
   placebo.

   The benefits of placebo treatment are, of course, not limited to
   psychiatry. In a review of hypertension therapy, it was documented that
   active pharmacologic agents were associated with a 40% to 60% rate of
   reducing blood pressure to the normal range, while placebo was
   associated with a 25% success rate.^7 Some neurologic conditions,
   asthma, and certain pain problems are also responsive to a placebo
   effect.

   What is a placebo response?

   In my opinion, the term placebo is misleading. In fact, patients who
   receive "placebo" treatment get much more than a sugar pill, whether
   they are enrolled in a placebo-controlled clinical trial or are the
   recipients of ordinary medical care. "Treatment situation" is a more
   evocative term than "placebo treatment," and it includes several
   essential elements associated with healing, as shown in Table 1.

                          Table 1
                          Elements of the treatment
                          situation
                          Recognized healer
                          Healing symbols
                          Evaluation
                          Healing rituals
                          Diagnosis
                          Prognosis
                          Plausible treatment

   All these elements, including healing symbols and rituals, evaluations,
   and discussions of diagnosis and prognosis, have an important role and
   are part of the placebo treatment or treatment situation. Hippocrates
   said that physicians should make frequent visits with their patients,
   inquire into all particulars of their situations, and learn about
   prognosis. The goal was to inspire confidence among patients so that
   they would feel comfortable entrusting their care to the physician.

   As an example, consider how patients respond to diagnostic tests. In a
   1981 paper that appeared in the Annals of Internal Medicine, clinical
   outcomes were assessed in a group of 176 patients who had chest pain
   that was considered nonspecific.^8 Participants in this study were
   randomized to have either routine ECG and serum creatine phosphokinase
   tests or to have no diagnostic tests. Short-term disability was
   reported by fewer patients (20%) in the test group than in the patients
   who received no tests (46%); this difference was statistically
   significant. Diagnostic tests were an independent predictor of
   recovery. More than half (57%) of the patients in the test group felt
   that the care they received was "better than usual." Fewer than one
   third of the patients who did not receive tests felt this way.^8 This
   is evidence that doing some simple testing often has an impact on how
   people feel.

   Similarly, a study conducted in New Zealand suggests the importance of
   a formality such as writing on a prescription pad. A group of 456
   sedentary patients were given verbal recommendations to increase their
   physical activity levels. Then they were randomized to a written
   exercise prescription or to a verbal advice group. The number of people
   in both groups who engaged in physical activity increased markedly
   after 6 weeks, but more participants in the written prescription than
   the verbal advice group were active. The investigators concluded that a
   written exercise prescription was an important adjunct in getting their
   patients to increase their physical activity levels.^9 In our culture,
   the written prescription has a large symbolic impact.

   Placebo response vs placebo effect

   No doubt some of the improvements observed in placebo-treated patients
   occur simply because of the passage of time. Many of the conditions
   that are most placebo-responsive, including insomnia, pain, asthma,
   hypertension, and depression, are by nature fluctuating illnesses. Some
   of the improvement we see associated with placebo is a result of
   regression to the mean. Nonethe- less, considerable evidence suggests
   that placebo treatment actually adds something that goes beyond the
   mere passage of time. Some would propose that the placebo effect should
   be defined as the placebo response minus the no-treatment response, or
   minus the changes that occurred simply as the result of waiting or the
   passage of time. Just as we say that the drug effect is the response
   that you obtain with a drug minus the placebo response, we can also say
   that the placebo effect is what we obtain from a placebo response minus
   what you would have gotten if no treatment of any kind were attempted.

   Mechanism of action

   The conditions that seem to be most likely to respond to placebo are
   those in which psychological distress plays an important role either in
   the exacerbation or expression of symptoms. Examples include
   depression, anxiety disorders, asthma, and painful conditions. Much of
   what we offer in the treatment situation for these conditions reduces
   distress. Obtaining a diagnosis and getting help from a recognized
   healing authority, an explanation for symptoms, and a plausible
   treatment are factors that alleviate distress. It is important to
   recall the distinction between illness and disease. Illness refers to
   the distress experienced by the patient, including symptoms,
   discouragement, and anxiety. Disease refers to objective evidence--for
   example, that which the physician observes in test results and imaging
   studies.

   Placebos tend to help illness--but how? Expectation has been subjected
   to the most study. Conditioning, endorphin release, and distress relief
   have also been considered, as shown in Table 2. With regard to
   expectation, it is clear that people experience what they expect to
   experience. Double-blind studies have demonstrated that when people
   receive a drink that they are told contains alcohol, they experience
   some of the effects of alcohol ingestion, including some of the
   physiologic effects.^10 Test subjects who are given decaffeinated
   coffee but are told that it is fully caffeinated exhibit improved
   reaction time and alertness.^10

                             Table 2
                             How placebos work
                             Expectation
                             Conditioning
                             Endorphins
                             Relief of distress

   Expectation has a profound effect on what people experience as a result
   of treatment. Until recently, the prevailing opinion held that these
   findings could be explained by patients telling physicians what they
   thought they wanted to hear or by patients imagining that they felt
   better. However, the results of several brain imaging studies suggest
   that expectation has a neuroanatomic and neurophysiologic basis.^11,12
   Conditioning also has a strong impact. Responses to chemotherapy are an
   example. After patients have had 1 or 2 infusions of a chemotherapeutic
   agent that caused nausea, they often begin to feel the onset of nausea
   as soon as they enter the facility where the medications are
   administered. We are aware of patients with asthma whose airways seem
   to open as soon as they see their nebulizers.

   Conditioned responses are also seen in animals. In rats that have been
   the recipients of long-term amphetamine administration, extreme
   locomotor responses persist even when placebo is substituted for the
   amphetamine. In some pain experiments, placebos may increase endorphin
   levels, and placebo analgesia can sometimes be blocked by naloxone.

   An intriguing study conducted in patients with idiopathic Parkinson
   disease sheds more light on conditioning and expectation. These
   patients had been implanted with stimulating electrodes. Not
   surprisingly, motor performance diminished in these patients within 30
   minutes of the time the stimulators were turned off. After this
   exercise was conducted, a sham turning-off procedure was conducted:
   Patients were told the stimulators were being shut off, but they
   actually remained on. Even so, motor velocity decreased. This is an
   example of the nocebo effect, in which a negative event happens as a
   result of a negative expectation. In another experiment, patients were
   told that the stimulators would be turned back on. Although the
   stimulators actually remained off, patients experienced better motor
   function. Although the expectation was not as powerful as the
   stimulator itself, the results reveal much about the ability of
   expectation to fuel treatment results.^13

   The power of conditioning is demonstrated by the results of a study of
   24 patients with mild to moderate hypertension who were randomized to
   receive placebo, atenolol, or no treatment. Before drug treatment was
   administered, blood pressure was similar in patients taking placebo and
   patients taking nothing. After patients had taken atenolol for a week,
   use of placebo caused a significantly greater antihypertensive response
   than receiving no treatment. The investigators concluded that the
   placebo response obtained after atenolol had been administered was not
   a simple residual drug effect.^14

   In a study conducted among men with unipolar depression, changes in
   brain glucose metabolism were measured by using positron emission
   to-mography. Similarities and differences were assessed among patients
   receiving placebo and fluoxetine. A strong placebo response went
   hand-in-hand with regional metabolic increases involving the
   prefrontal, anterior cingulate, premotor, parietal, posterior insula,
   and posterior cingulate areas; metabolic decreases occurred in the
   subgenual cingulate, parahippocampus, and thalamus. These areas of
   metabolic change overlapped with those that were observed in patients
   who had responded to fluoxetine. Among patients who responded to
   fluoxetine, however, changes were also seen in the brainstem, striatum,
   anterior insula, and hippocampus. The authors concluded that changes in
   certain areas of the brain are probably essential to the remission of
   depression, whether active drug or placebo is administered. Patients
   who respond to fluoxetine experience brain changes that do not occur in
   patients who do not respond to placebo. Patients who respond to placebo
   experience brain changes that are similar to but less extensive than
   those that occur in response to fluoxetine. These changes are different
   from those seen in patients who do not respond to placebo.^15

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   The Placebo Effect

   By Logan Wright
   In drug testing, a control group is necessary so that the results in
   the experimental group can be compared against something. Both groups
   are ideally identical aside from the experimental variable. The
   experimental group receives the drug, whereas the control group
   receives a placebo.
   The placebo is a pill or medication that appears to be the drug, but
   does not actually contain any active ingredients and thus has no effect
   on the user. Thus, both groups believe they are taking the drug and
   both groups expect to experience the effects.
   The trouble is, the placebo groups frequently do experience the drug's
   effects, sometimes as much as those taking the active drug! This
   baffling phenomenon, known as the placebo effect, is not limited to
   drug trials, however. Most people experience the placebo effect in
   various ways everyday.
   How our own psychological outlook can affect health is still mostly
   unknown, but you can be sure there are some great brains beavering over
   it right at this very moment.
   More information: Placebo effect: harnessing your mind's power to heal
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The Placebo Effect: A treatment of the mind?

   Posted on December 16, 2012 by thebrainbank

   When a patient known as Mr. Wright was diagnosed with terminal lymphoma
   (cancer of the lymphatic system), the doctors battling to prolong his
   life were ultimately left with no option but to try a new
   ‘controversial’ anti-cancer drug – Krebiozen. Although doctors and
   scientists remained unconvinced about the drugs effectiveness, Mr
   Wright was confident that it would lead to an improvement of his
   condition. Despite being bed-bound and in extremely poor health, just
   three days after his first treatment he had enough energy to get out of
   bed. After ten days his tumours had shrunk significantly in size, and
   he was well enough to go home.

   So what was this mysterious drug, and what caused the remission of his
   symptoms?

   Krebiozen was marketed and endorsed in the 1950s by several physicians
   who claimed the drug possessed anti-cancer properties. One study
   claimed that of 22 patients with diagnosed terminal cancer, 14 remained
   alive after treatment. However, other scientists failed to reproduce
   these results and ultimately decided that the drug was of no benefit to
   cancer sufferers. The National Institute of Cancer verified this
   decision after finding that the drug consisted of nothing more than
   simple amino acids and mineral oil, with no active ingredients.

   This drug was actually a placebo! Placebo treatments are usually given
   to patients in the form of sugar pills, but can also include injections
   and sham surgery. The key to the placebo’s success is ensuring the
   patient believes the treatment will improve their condition. Belief in
   the treatment can lead to a perceived or actual improvement of the
   condition.

   The so-called ‘placebo effect’ appears, at first glance, to make no
   sense whatsoever. How could a simple sugar pill alleviate serious
   medical symptoms? The answer may be as simple as a positive mental
   attitude.  A patient’s mental well-being and perception of of their
   illness may be an important factor in influencing their medical
   prognosis. This is a remarkable concept, but how is it biologically
   possible? One suggestion is that the notion of medical intervention
   creates a mental cue which acts to kick-start an immune response within
   our bodies leading to self-healing. A similar response to seemingly
   unrelated external cues has in fact also been observed in Siberian
   Hamsters. When exposed to light levels which mimic winter days,
   hamsters show a depression of their immune response. If, however, they
   are exposed to lights mimicking summer days, the immune response
   increases and healing begins.

   I was first inspired to write this article by a programme I watched a
   few weeks ago on Channel 4 titled Derren Brown: Fear and Faith. This
   show demonstrated the power of the placebo effect through a fake
   clinical trial. Subjects on this trial were given a placebo drug
   (Rumyodin) and were told that it could inhibit feelings of fear. Over
   the course of few weeks, we saw each of the subjects overcome their
   respective fears ranging from heights and confrontation to singing in
   public. The drug was also effective as a cure for smoking and
   allergies. The strength of the placebo was enhanced by the very
   convincing story behind the drug’s development, including a fictitious
   pharmaceutical company and the use of doctors to administer the drug.
   The placebo’s extremely powerful effects were probably due to this
   attention to detail, meaning subjects were convinced that the treatment
   would work.

   So if placebos can offer such amazing results without the need for any
   active ingredient and all the side effects these may bring, why are
   they not used more regularly?

   The ability of a placebo to alleviate symptoms is variable both in how
   often they succeed and the strength of the resulting symptom
   alleviation. Placebos appear to be more effective when symptoms are
   subjective such as pain or nausea and less effective for non-subjective
   symptoms such as abnormal blood pressure or heart rate.

   A recent study in the US has suggested that genes may also play an
   important role in deciding whether or not an individual responds to a
   placebo. Preliminary results indicate that if a particular gene is
   present, individuals with irritable bowel syndrome are more likely to
   respond to placebo acupuncture. Whether this effect may be replicated
   for other conditions is unclear. However, these results do offer an
   explanation as to why some people are more susceptible to the placebo
   effect than others.

   A study from 1985 hypothesised that the placebo effect relies heavily
   upon a belief that the medicine will make you feel better. Indeed, one
   study showed that the attitude of the prescribing doctor towards both
   the drug and the patient significantly altered the patients prognosis.
   In this study patient’s responses to a placebo rose from 44% to 62%
   when the doctor prescribing the treatment made a conscious effort to be
   positive.

   This means that scientists are faced with a paradox when it comes to
   the use of placebos. Although there are clear ethical issues arising
   from their use, such as the controversy of introducing dishonesty into
   the patient-doctor relationship, ethical issues also arise from NOT
   using placebos. Is it unethical not to use something that could help
   improve a patient’s health? Despite this, the UK Parliamentary
   Committee for Science and Technology think that the placebo effect is
   unreliable and should not be used as a sole treatment on the NHS. In
   contrast, a study of GPs in Denmark has shown that 48% had previously
   prescribed placebo as treatments at least 10 times over the last year.
   Moreover, a study in 2004 uncovered that approximately 60% of
   physicians in Israel has used placebos in their practice.

   What is important to remember, is that placebos are not a
   ‘one-size-fits-all’ cure that works for everyone. The effect that
   placebos have can be highly variable and often unreliable. Whilst some
   people respond positively to treatment with placebos, others experience
   no change to their condition. This positive effect appears to depend
   not only on the type of ailment the patient is suffering with, but also
   their mental attitude towards the treatment. However, what is clear is
   that a lot more research needs to be carried out to investigate exactly
   how and why placebos work, and why their success is so variable.

   IFRAME:
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   h=0&showinfo=1&iv_load_policy=1&wmode=transparent

   Post by: Sam Lawrence
   Print Friendly

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   about who we are see the our 'about' page. You can also find us on
   twitter @brainbankmanc or email us brainbankmanc@gmail.com.
   View all posts by thebrainbank →
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3 Responses to The Placebo Effect: A treatment of the mind?

    1. Jan says:
       December 21, 2012 at 1:37 am
       “What is important to remember, is that placebos are not a
       ‘one-size-fits-all’ cure that works for everyone. The effect that
       placebos have can be highly variable and often unreliable. Whilst
       some people respond positively to treatment with placebos, others
       experience no change to their condition. ”
       The same can be said of any individual medicine and yet we
       prescribe them almost indiscriminately.
       Reply
    2. Jayarava says:
       December 21, 2012 at 9:35 am
       Great. I was particularly pleased to see the ethical question of
       not trying a placebo raised – at least you are taking it a bit
       seriously. Isn’t the placebo effect interesting? We do know that a
       lot of things can stimulate the immune system – though this itself
       has given rise to many bogus claims. It sounds like a testable
       hypothesis. Is there anyone testing it? Does the immune system
       suddenly shrink a tumour because of a positive mental attitude?
       Ethics questions aside, it should be testable shouldn’t it? Though
       how you would isolate the various factors in spontaneous remission
       and recovery from cancer I’m not sure, I’ve no doubt scientists
       will find a way if they bother to look. Not much money in it for
       the drug companies though eh?
       I think Derren Brown’s experiments detracted from the main point
       here. The curing of purely psychological effects, by a well known
       hypnotist, is much less interesting. If I was conducting a study I
       wouldn’t let Brown within 100 miles and a triple blind of the
       participants. I’ve watched a lot of his shows and he can do amazing
       things, but he’s a wild card.
       This is one in a small series of articles that have come out in the
       last 5-10 years which acknowledge physical alleviation of symptoms
       and sometimes cures for illness based on the patient’s belief that
       they have been given an effective treatment. It’s start, but I
       still see a lot of dismissal of such things as “merely placebo
       effect” as though it is inconsequential. Shrinking tumours are
       hardly inconsequential. Nor are many of the other effects that are
       now documented to quite a high standard of evidence gathering.
       I’d like to recommend a book by an anthropologist. “The End of
       Magic” by Ariel Glucklich. He studied tantric healers in modern day
       Varanasi, and came up with an interesting take on how they work to
       help with illness. It’s not medical science, but it might help to
       provide clues into the kinds mental changes that need to take place
       for a placebo to be effective.
       Reply
    3. Mark Uribe says:
       December 23, 2012 at 7:05 am
       Surely the point here is that the key factor is a positive
       optimistic attitude, whether the “placebo” is a pill, a self help
       book, a religious belief, humour, a supportive partner, a pet,
       etc.. If I’m not mistaken, all these things have been shown to have
       healing benefits, so let’s not talk about pulling the wool over
       people’s eyes, but be open and make people aware how important
       one’s own attitude is and find ways to give people the support
       needed to keep positive.
       Reply

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   Clinical Trials

GlaxoSmithKline's Duchenne MD drug mirrors placebo effect in PhIII

   October 7, 2013 | By John Carroll
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   Over the weekend GlaxoSmithKline ($GSK) detailed the decisive failure
   of its ambitious Phase III study for drisapersen, a new drug designed
   to treat Duchenne muscular dystrophy. John Kraus, GSK's medical leader
   for drisapersen, unveiled more data from the failed study on the
   exon-skipping technology, which fell short not only on its primary
   endpoint for improved walking distances in a 6-minute test but also
   flunked out on three separate secondary endpoints, with the outcomes
   looking almost identical in each case with a placebo.

   After 48 weeks of therapy, says Kraus, the drisapersen group suffered a
   decline in walking distance, just as the placebo arm did. The decline
   was 10.3 meters in the drug arm's favor, falling short of a significant
   improvement and well off the more than 30-meter improvement seen in
   Phase II. Using the North Star Ambulatory Assessment test, the placebo
   arm scored 6.7 compared to a close 7.2 score for drisapersen. A
   velocity test gauging the time to climb four stairs was also virtually
   identical--a 0.12 decline in the placebo arm and a 0.14 decline in the
   drug group. There was a near mirror-image decline in the rate of
   patients' 10-meter walk/run velocity gauge.

   Kraus says the trial was well run and the quality outcomes they
   measured were good, providing a clear read out on the drug for the
   group they studied. Now investigators are going back over the data to
   see if a subset of patients benefited. And they are also running
   analyses on dystrophin expression to see how the therapy--in-licensed
   from the Dutch biotech Prosensa--influenced a key biomarker for the
   disease.

   "We need to understand if there may be a subpopulation that could have
   derived a benefit from drisapersen," Kraus tells FierceBiotech. "We are
   currently running analyses to help us understand."

   Subpopulation analysis is common in drug development, but it's far from
   ideal. A positive sign in a particular group might open the door to a
   new study geared for a narrow segment of the patient population, which
   has no meaningful therapy to rely on. But it's no guarantee of even
   limited success.

   Investors have been paying particularly close attention to the
   drisapersen data to see how it might reflect on eteplirsen, a DMD drug
   in development at Sarepta ($SRPT). Sarepta shares have soared on the
   positive outcome seen in a very small study of the drug, and the
   biotech believes it has a shot at an accelerated approval based on that
   study. Right now, eteplirsen is the leading therapy in the DMD field,
   and there's nothing in GlaxoSmithKline's latest data that changes any
   of that.

   Related Articles:
   Muscular dystrophy drug from GlaxoSmithKline, Prosensa fails PhIII
   New DMD data give Sarepta an edge in GlaxoSmithKline showdown
   Glaxo grabs coveted breakthrough drug status for muscular dystrophy
   drug
   Amid cheers and jeers, GlaxoSmithKline reveals Duchenne drug hit PhII
   goal
   Filed Under
   drisapersen, Duchenne muscular dystrophy, GlaxoSmithKline

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