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A placebo ( ) can be roughly defined as a
sham Sham may refer to: Arabic use * Al-Sham or Shām (شام), the Arabic term for the Greater Syria region, known in English as the Levant or the eastern Mediterranean, which includes the modern countries of Syria, Lebanon, Palestine, Jordan, Cyprus ...
medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline),
sham surgery Sham surgery (or placebo surgery) is a faked surgical intervention that omits the step thought to be therapeutically necessary. In clinical trials of surgical interventions, sham surgery is an important scientific control. This is because it isol ...
, and other procedures. Placebos are used in
randomized clinical trials A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
to test the efficacy of
medical treatments Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...
. In a placebo-controlled trial, any change in the control group is known as the ''placebo response'', and the difference between this and the result of no treatment is the ''placebo effect''. Placebos in clinical trials should ideally be indistinguishable from so-called verum treatments under investigation, except for the latter's particular hypothesized medicinal effect. This is to shield test participants (with their
consent Consent occurs when one person voluntarily agrees to the proposal or desires of another. It is a term of common speech, with specific definitions used in such fields as the law, medicine, research, and sexual consent. Consent as understood i ...
) from knowing who is getting the placebo and who is getting the treatment under test, as patients' and clinicians' expectations of
efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as '' effectiveness'', and it has often been used synonymously, although in pharmacology a distinction is now often made betwee ...
can influence results. The idea of a placebo effect was discussed in 18th century psychology, but became more prominent in the 20th century. Modern studies find that placebos can affect some outcomes such as
pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
and
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...
, but otherwise do not generally have important clinical effects. Improvements that patients experience after being treated with a placebo can also be due to unrelated factors, such as
regression to the mean Regression or regressions may refer to: Arts and entertainment * ''Regression'' (film), a 2015 horror film by Alejandro Amenábar, starring Ethan Hawke and Emma Watson * ''Regression'' (magazine), an Australian punk rock fanzine (1982–1984) * ...
(a statistical effect where an unusually high or low measurement is likely to be followed by a less extreme one). The use of placebos in clinical medicine raises ethical concerns, especially if they are disguised as an active treatment, as this introduces dishonesty into the doctor–patient relationship and bypasses
informed consent Informed consent is an applied ethics principle that a person must have sufficient information and understanding before making decisions about accepting risk. Pertinent information may include risks and benefits of treatments, alternative treatme ...
. Placebos are also popular because they can sometimes produce relief through psychological mechanisms (a phenomenon known as the "placebo effect"). They can affect how patients perceive their condition and encourage the body's chemical processes for relieving pain and a few other symptoms, but have no impact on the
disease A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...
itself.


Etymology and definition

The
Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...
term (pronounced or ) means '' shall be pleasing''. The definition of ''placebo'' has been debated. One definition states that a treatment process is a placebo when none of the characteristic treatment factors are effective (remedial or harmful) in the
patient A patient is any recipient of health care services that are performed by Health professional, healthcare professionals. The patient is most often Disease, ill or Major trauma, injured and in need of therapy, treatment by a physician, nurse, op ...
for a given
disease A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...
. In a clinical trial, a ''placebo response'' is the measured response of subjects to a placebo; the ''placebo effect'' is the difference between that response and no treatment. The placebo response may include improvements due to natural healing, declines due to natural disease progression, the tendency for people who were temporarily feeling either better or worse than usual to return to their average situations (
regression toward the mean In statistics, regression toward the mean (also called regression to the mean, reversion to the mean, and reversion to mediocrity) is the phenomenon where if one sample of a random variable is extreme, the next sampling of the same random var ...
), and errors in the clinical trial records, which can make it appear that a change has happened when nothing has changed. It is also part of the recorded response to any active medical intervention. Measurable placebo effects may be either ''objective'' (e.g. lowered
blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
) or ''subjective'' (e.g. a lowered perception of pain).


Effects

Placebo can improve patient-reported outcomes such as
pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...
and
nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...
. A 2001 meta-analysis of the placebo effect looked at trials in 40 different medical conditions, and concluded the only one where it had been shown to have a significant effect was for pain. Another Cochrane review in 2010 suggested that placebo effects are apparent only in subjective, continuous measures, and in the treatment of pain and related conditions. The review found that placebos do not appear to affect the actual diseases, or outcomes that are not dependent on a patient's perception. The authors,
Asbjørn Hróbjartsson Asbjørn Hróbjartsson is a Danish medical researcher. He is Professor of Evidence-Based Medicine and Clinical Research Methodology at the University of Southern Denmark, as well as head of research at Odense University Hospital's Center for Evi ...
and Peter C. Gøtzsche, concluded that their study "did not find that placebo interventions have important clinical effects in general". This interpretation has been subject to criticism, as the existence of placebo effects seems undeniable. For example, recent research has linked placebo interventions to improved motor functions in patients with
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
. Other objective outcomes affected by placebos include
immune In biology, immunity is the state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease. Immunity may occur naturally or be produced by prior exposure or immunization. Innate and adaptive ...
and
endocrine The endocrine system is a messenger system in an organism comprising feedback loops of hormones that are released by internal glands directly into the circulatory system and that target and regulate distant organs. In vertebrates, the hypotha ...
parameters, end-organ functions regulated by the
autonomic nervous system The autonomic nervous system (ANS), sometimes called the visceral nervous system and formerly the vegetative nervous system, is a division of the nervous system that operates viscera, internal organs, smooth muscle and glands. The autonomic nervo ...
, and
sport Sport is a physical activity or game, often Competition, competitive and organization, organized, that maintains or improves physical ability and skills. Sport may provide enjoyment to participants and entertainment to spectators. The numbe ...
performance. Measuring the extent of the placebo effect is difficult due to confounding factors. Gøtzsche's biographical article has further references related to this work. For example, a patient may feel better after taking a placebo due to regression to the mean (i.e. a natural recovery or change in symptoms), but this can be ruled out by comparing the placebo group with a no treatment group (as all the placebo research does). It is harder still to tell the difference between the placebo effect and the effects of
response bias Response bias is a general term for a wide range of tendencies for participants to respond inaccurately or falsely to questions. These biases are prevalent in research involving participant self-report, such as structured interviews or surveys. R ...
,
observer bias Observer bias is one of the types of detection bias and is defined as any kind of systematic divergence from accurate facts during observation and the recording of data and information in studies. The definition can be further expanded upon to inc ...
and other flaws in trial methodology, as a trial comparing placebo treatment and no treatment will not be a
blinded experiment In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expec ...
. In their 2010 meta-analysis of the placebo effect, Asbjørn Hróbjartsson and Peter C. Gøtzsche argue that "even if there were no true effect of placebo, one would expect to record differences between placebo and no-treatment groups due to bias associated with lack of blinding". One way in which the magnitude of placebo
analgesia Pain management is an aspect of medicine and health care involving relief of pain (pain relief, analgesia, pain control) in various dimensions, from acute and simple to chronic and challenging. Most physicians and other health professionals ...
can be measured is by conducting "open/hidden" studies, in which some patients receive an analgesic and are informed that they will be receiving it (open), while others are administered the same drug without their knowledge (hidden). Such studies have found that analgesics are considerably more effective when the patient knows they are receiving them.


Factors influencing the power of the placebo effect

A review published in ''
JAMA Psychiatry ''JAMA Psychiatry'' (until 2013: ''Archives of General Psychiatry'') is a monthly peer-reviewed medical journal published by the American Medical Association. It covers research in psychiatry, mental health, behavioral sciences, and related fields. ...
'' found that, in trials of antipsychotic medications, the change in response to receiving a placebo had increased significantly between 1960 and 2013. The review's authors identified several factors that could be responsible for this change, including inflation of baseline scores and enrollment of fewer severely ill patients. Another analysis published in ''Pain'' in 2015 found that placebo responses had increased considerably in
neuropathic pain Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuo ...
clinical trials conducted in the United States from 1990 to 2013. The researchers suggested that this may be because such trials have "increased in study size and length" during this time period. Individual differences in personality traits may influence susceptibility to placebo and nocebo (negative placebo) effects. People with a more optimistic outlook tend to exhibit stronger placebo responses, while those with higher levels of anxiety are more likely to experience nocebo effects.
Children A child () is a human being between the stages of childbirth, birth and puberty, or between the Development of the human body, developmental period of infancy and puberty. The term may also refer to an unborn human being. In English-speaking ...
seem to have a greater response than
adults An adult is an animal that has reached full growth. The biological definition of the word means an animal reaching sexual maturity and thus capable of reproduction. In the human context, the term ''adult'' has meanings associated with social and ...
to placebos. The administration of the placebos can determine the placebo effect strength. Studies have found that taking more pills would strengthen the effect. Capsules appear to be more influential than pills, and injections are even stronger than capsules. Some studies have investigated the use of placebos where the patient is fully aware that the treatment is inert, known as an '' open-label placebo''. Clinical trials found that open-label placebos may have positive effects in comparison to no treatment, which may open new avenues for treatments, but a review of such trials noted that they were done with a small number of participants and hence should be interpreted with "caution" until further, better-controlled trials are conducted. An updated 2021 systematic review and meta-analysis based on 11 studies also found a significant, albeit slightly smaller overall effect of open-label placebos, while noting that "research on OLPs is still in its infancy". If the person dispensing the placebo shows their care towards the patient, is friendly and sympathetic, or has a high expectation of a treatment's success, then the placebo is more effectual.


Depression

In 2008, a
meta-analysis Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...
led by psychologist Irving Kirsch, analyzing data from the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
(FDA), concluded that 82% of the response to antidepressants was accounted for by placebos. However, other authors expressed doubts about the used methods and the interpretation of the results, especially the use of 0.5 as the cut-off point for the
effect size In statistics, an effect size is a value measuring the strength of the relationship between two variables in a population, or a sample-based estimate of that quantity. It can refer to the value of a statistic calculated from a sample of data, the ...
. A complete reanalysis and recalculation based on the same FDA data found that the Kirsch study had "important flaws in the calculations". The authors concluded that although a large percentage of the placebo response was due to expectancy, this was not true for the active drug. Besides confirming drug effectiveness, they found that the drug effect was not related to depression severity. 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. In the continuation phase however, patients on placebo relapsed significantly more often than patients on antidepressants.


Psychedelics

It has been proposed that psychedelics used for therapeutic purposes may act as
active Active may refer to: Music * ''Active'' (album), a 1992 album by Casiopea * "Active" (song), a 2024 song by Asake and Travis Scott from Asake's album ''Lungu Boy'' * Active Records, a record label Ships * ''Active'' (ship), several com ...
"super placebos".


Negative effects

A phenomenon opposite to the placebo effect has also been observed. When an inactive substance or treatment is administered to a recipient who has an expectation of it having a ''negative'' impact, this intervention is known as a nocebo (
Latin Latin ( or ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally spoken by the Latins (Italic tribe), Latins in Latium (now known as Lazio), the lower Tiber area aroun ...
= "I shall harm"). A nocebo effect occurs when the recipient of an inert substance reports a negative effect or a worsening of symptoms, with the outcome resulting not from the substance itself, but from negative expectations about the treatment. Another negative consequence is that placebos can cause
side-effects In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually used ...
associated with real treatment. Withdrawal symptoms can also occur after placebo treatment. This was found, for example, after the discontinuation of the
Women's Health Initiative The Women's Health Initiative (WHI) was a series of clinical studies initiated by the U.S. National Institutes of Health (NIH) in 1991, to address major health issues causing morbidity and mortality in postmenopausal women. It consisted of three ...
study of
hormone replacement therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...
for
menopause Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...
. Women had been on placebo for an average of 5.7 years. Moderate or severe withdrawal symptoms were reported by 4.8% of those on placebo compared to 21.3% of those on hormone replacement.


Ethics


In research trials

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 Informed consent is an applied ethics principle that a person must have sufficient information and understanding before making decisions about accepting risk. Pertinent information may include risks and benefits of treatments, alternative treatme ...
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 The Declaration of Helsinki (DoH, ) is a set of ethical principles regarding human experimentation developed originally in 1964 for the medical community by the World Medical Association (WMA). It is widely regarded as the cornerstone document o ...
. 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. Some suggest that existing medical treatments should be used instead of placebos, to avoid having some patients not receive medicine during the trial.


In medical practice

The practice of doctors prescribing placebos that are disguised as real medication is controversial. A chief concern is that it is deceptive and could harm the doctor–patient relationship in the long run. While some say that blanket consent, or the general consent to unspecified treatment given by patients beforehand, is ethical, others argue that patients should always obtain specific information about the name of the drug they are receiving, its side effects, and other treatment options. This view is shared by some on the grounds of patient autonomy. There are also concerns that legitimate doctors and pharmacists could open themselves up to charges of fraud or malpractice by using a placebo. Critics also argued that using placebos can delay the proper diagnosis and treatment of serious medical conditions. Despite the abovementioned issues, 60% of surveyed physicians and head nurses reported using placebos in an Israeli study, with only 5% of respondents stating that placebo use should be strictly prohibited. A ''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." 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.Doctors Struggle With Tougher-Than-Ever Dilemmas: Other Ethical Issues
Author: Leslie Kane. 11/11/2010
Referring specifically to
homeopathy Homeopathy or homoeopathy is a pseudoscientific system of alternative medicine. It was conceived in 1796 by the German physician Samuel Hahnemann. Its practitioners, called homeopaths or homeopathic physicians, believe that a substance that ...
, the
House of Commons of the United Kingdom The House of Commons is the lower house of the Parliament of the United Kingdom. Like the upper house, the House of Lords, it meets in the Palace of Westminster in London, England. The House of Commons is an elected body consisting of 650 memb ...
Science and Technology Committee has stated: In his 2008 book '' Bad Science'',
Ben Goldacre Ben Michael Goldacre (born 20 May 1974) is a British physician, academic and science writer. He is the first Bennett Professor of Evidence-Based Medicine and director of the Bennett Institute for Applied Data Science at the University of Oxford ...
argues that instead of deceiving patients with placebos, doctors should use the placebo effect to enhance effective medicines.
Edzard Ernst Edzard Ernst (born 30 January 1948) is a retired British-German academic physician and researcher specializing in the study of complementary and alternative medicine. He was Professor of Complementary Medicine at the University of Exeter, the wo ...
has argued similarly that "As a good doctor you should be able to transmit a placebo effect through the compassion you show your patients." In an opinion piece about homeopathy, Ernst argues that it is wrong to support
alternative medicine Alternative medicine refers to practices that aim to achieve the healing effects of conventional medicine, but that typically lack biological plausibility, testability, repeatability, or supporting evidence of effectiveness. Such practices are ...
on the basis that it can make patients feel better through the placebo effect. His concerns are that it is deceitful and that the placebo effect is unreliable. Goldacre also concludes that the placebo effect does not justify alternative medicine, arguing that unscientific medicine could lead to patients not receiving prevention advice. Placebo researcher Fabrizio Benedetti also expresses concern over the potential for placebos to be used unethically, warning that there is an increase in "quackery" and that an "alternative industry that preys on the vulnerable" is developing.


Mechanisms

The mechanism for how placebos could have effects is uncertain. From a sociocognitive perspective, intentional placebo response is attributed to the “ritual effect” that induces anticipation for transition to a better state. A placebo presented as a
stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
may trigger an effect on
heart rhythm ''Heart Rhythm'' is a peer-reviewed medical journal published by Elsevier that covers the study and management of cardiac arrhythmia. It is the official journal of the Heart Rhythm Society, the Cardiac Electrophysiology Society, and thPediatric & ...
and
blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...
, but when administered as a
depressant Depressants, also known as central nervous system depressants, or colloquially known as "downers", are drugs that lower neurotransmission levels, decrease the electrical activity of brain cells, or reduce arousal or stimulation in various ...
, the opposite effect.


Psychology

In psychology, the two main hypotheses of the placebo effect are expectancy theory and
classical conditioning Classical conditioning (also respondent conditioning and Pavlovian conditioning) is a behavioral procedure in which a biologically potent Stimulus (physiology), stimulus (e.g. food, a puff of air on the eye, a potential rival) is paired with a n ...
. 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. 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. Similarly, the appearance of effect can result from classical conditioning, wherein a placebo and an actual stimulus are used simultaneously until the placebo is associated with the effect from the actual stimulus. Both conditioning and expectations play a role in placebo effect, and make different kinds of contributions. Conditioning has a longer-lasting effect, and can affect earlier stages of information processing. Those who think a treatment will work display a stronger placebo effect than those who do not, as evidenced by a study of acupuncture. Additionally,
motivation Motivation is an mental state, internal state that propels individuals to engage in goal-directed behavior. It is often understood as a force that explains why people or animals initiate, continue, or terminate a certain behavior at a particul ...
may contribute to the placebo effect. The active goals of an individual changes their somatic experience by altering the detection and interpretation of expectation-congruent symptoms, and by changing the behavioral strategies a person pursues. 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.


Placebo analgesia

Functional imaging Functional imaging (or physiological imaging) is a medical imaging technique of detecting or measuring changes in metabolism, blood flow, regional chemical composition, and absorption. As opposed to structural imaging, functional imaging center ...
upon placebo analgesia suggests links to the activation, and increased functional correlation between this activation, in the
anterior cingulate In human brains, the anterior cingulate cortex (ACC) is the frontal part of the cingulate cortex that resembles a "collar" surrounding the frontal part of the corpus callosum. It consists of Brodmann areas 24, 32, and 33. It is involved in c ...
, prefrontal, orbitofrontal and insular cortices,
nucleus accumbens The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...
,
amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...
, the
brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...
's periaqueductal gray matter, and the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...
. Since 1978, it has been known that placebo analgesia depends upon the release of endogenous opioids in the brain. Such analgesic placebos activation changes processing lower down in the brain by enhancing the descending inhibition through the periaqueductal gray on spinal nociceptive reflexes, while the expectations of anti-analgesic nocebos acts in the opposite way to block this. 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". "Diseases lacking major 'top-down' or cortically based regulation may be less prone to placebo-related improvement".


Brain and body

In conditioning, a neutral stimulus
saccharin Saccharin, also called saccharine, benzosulfimide, or E954, or used in saccharin sodium or saccharin calcium forms, is a non-nutritive artificial sweetener. Saccharin is a sultam that is about 500 times sweeter than sucrose, but has a bitter or ...
is paired in a drink with an agent that produces an unconditioned response. For example, that agent might be
cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
, which causes
immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
. After learning this pairing, the taste of saccharin by itself is able to cause immunosuppression, as a new conditioned response via neural top-down control. 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 Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
secretion. Recent reviews have argued that the placebo effect is due to top-down control by the brain for immunity and pain. 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". There has also been research aiming to understand underlying neurobiological mechanisms of action in pain relief,
immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
,
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
and depression. Dopaminergic pathways have been implicated in the placebo response in pain and depression.


Confounding factors

Placebo-controlled studies, as well as studies of the placebo effect itself, often fail to adequately identify confounding factors. False impressions of placebo effects are caused by many factors including: *
Regression to the mean Regression or regressions may refer to: Arts and entertainment * ''Regression'' (film), a 2015 horror film by Alejandro Amenábar, starring Ethan Hawke and Emma Watson * ''Regression'' (magazine), an Australian punk rock fanzine (1982–1984) * ...
(natural recovery or fluctuation of symptoms) * Additional treatments * Response bias from subjects, including scaling bias, answers of politeness, experimental subordination, conditioned answers; *
Reporting bias In epidemiology, reporting bias is defined as "selective revealing or suppression of information" by subjects (for example about past medical history, smoking, sexual experiences). In artificial intelligence research, the term reporting bias is u ...
from experimenters, including misjudgment and irrelevant response variables. * Non-inert ingredients of the placebo medication having an unintended physical effect


History

The word placebo was used in a medicinal context in the late 18th century to describe a "commonplace method or medicine" and in 1811 it was defined as "any medicine adapted more to please than to benefit the patient". Although this definition contained a derogatory implication it did not necessarily imply that the remedy had no effect. It was recognized in the 18th and 19th centuries that drugs or remedies often were perceived to work best while they were still novel: Placebos have featured in medical use until well into the twentieth century. An influential 1955 study entitled ''The Powerful Placebo'' firmly established the idea that placebo effects were clinically important, and were a result of the brain's role in physical health. A 1997 reassessment found no evidence of any placebo effect in the source data, as the study had not accounted for
regression to the mean Regression or regressions may refer to: Arts and entertainment * ''Regression'' (film), a 2015 horror film by Alejandro Amenábar, starring Ethan Hawke and Emma Watson * ''Regression'' (magazine), an Australian punk rock fanzine (1982–1984) * ...
.


Placebo-controlled studies

The placebo effect makes it more difficult to evaluate new treatments. 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. 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.


See also

* *
Homeopathy Homeopathy or homoeopathy is a pseudoscientific system of alternative medicine. It was conceived in 1796 by the German physician Samuel Hahnemann. Its practitioners, called homeopaths or homeopathic physicians, believe that a substance that ...
*
List of effects This is a list of names for observable phenomena that contain the word “effect”, amplified by reference(s) to their respective fields of study. A * Abscopal effect (cancer treatments) (immune system) (medical treatments) (radiation thera ...
*
List of topics characterized as pseudoscience This is a list of topics that have been characterized as pseudoscience by academics or researchers, either currently or in the past. Detailed discussion of these topics may be found on their main pages. These characterizations were made in the c ...
*
Nocebo A nocebo effect is said to occur when a patient's expectations for a treatment cause the treatment to have a worse effect than it otherwise would have. For example, when a patient anticipates a side effect of a medication, they can experience that ...
*
Placebo button A placebo button is a push-button or other control that appears to have functionality but has no physical effect when pressed. Such buttons can appear to work, by lighting up or otherwise reacting, which rewards the user by giving them an illusion ...
*
Royal Commission on Animal Magnetism The Royal Commission on Animal Magnetism involved two entirely separate and independent French Royal Commissions, each appointed by Louis XVI in 1784, that were conducted simultaneously by a committee composed of four physicians from the Univer ...
*
Self-fulfilling prophecy A self-fulfilling prophecy is a prediction that comes true at least in part as a result of a person's belief or expectation that the prediction would come true. In the phenomena, people tend to act the way they have been expected to in order to mak ...


References


Further reading

* * * *


External links


Program in Placebo Studies & Therapeutic Encounter (PiPS)
(
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts is a teaching hospital of Harvard Medical School and one of the founding members of Beth Israel Lahey Health. It was formed out of the 1996 merger of Beth Israel Hospital (f ...
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Harvard Medical School Harvard Medical School (HMS) is the medical school of Harvard University and is located in the Longwood Medical and Academic Area, Longwood Medical Area in Boston, Massachusetts. Founded in 1782, HMS is the third oldest medical school in the Un ...
) {{Authority control Clinical research Deception Mind–body interventions