![Cebocap](https://upload.wikimedia.org/wikipedia/commons/1/1c/Cebocap.jpg)
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value.
[ Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), ]sham surgery
Sham surgery (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 isolate ...
, and other procedures.
In general, placebos 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 negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
itself.[ Improvements that patients experience after being treated with a placebo can also be due to unrelated factors, such as ]regression to the mean
In statistics, regression toward the mean (also called reversion to the mean, and reversion to mediocrity) is the fact that if one sample of a random variable is extreme, the next sampling of the same random variable is likely to be closer to it ...
(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 a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatme ...
. While it was once assumed that this deception was necessary for placebos to have any effect, there is some evidence that placebos may have subjective effects even when the patient is aware that the treatment is a placebo (known as open-label placebo).
In drug testing and medical research, a placebo can be made to resemble an active medication or therapy so that it functions as a control
Control may refer to:
Basic meanings Economics and business
* Control (management), an element of management
* Control, an element of management accounting
* Comptroller (or controller), a senior financial officer in an organization
* Controllin ...
; this is to prevent the recipient or others from knowing (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 as used in such fields as the law, medicine, research, and sexual relationships. Consent as und ...
) whether a treatment is active or inactive, as expectations about 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 pragmatic clinical trial#Efficacy versu ...
can influence results. In a placebo-controlled
Placebo-controlled studies are a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed ...
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
any change in the control
Control may refer to:
Basic meanings Economics and business
* Control (management), an element of management
* Control, an element of management accounting
* Comptroller (or controller), a senior financial officer in an organization
* Controllin ...
group is known as the placebo response, and the difference between this and the result of no treatment is the placebo effect.[ Some researchers now recommend comparing the experimental treatment with an existing treatment when possible, instead of a placebo.]
The idea of a ''placebo effect''—a therapeutic outcome derived from an inert treatment—was discussed in 18th century psychology, but became more prominent in the 20th 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.[
]
Etymology
''Placebo'' (pronounced /plaˈkebo/ or /plaˈt͡ʃebo) is Latin
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
for 'Ishall be pleasing.'' It was used as a name for the Vespers
Vespers is a service of evening prayer, one of the canonical hours in Eastern Orthodox, Oriental Orthodox, Catholic Church, Catholic (both Latin liturgical rites, Latin and Eastern Catholic Churches, Eastern), Lutheranism, Lutheran, and Anglican ...
in the Office of the Dead
The Office of the Dead or Office for the Dead (in Latin, Officium Defunctorum) is a prayer cycle of the Canonical Hours in the Catholic Church, Anglican Church and Lutheran Church, said for the repose of the soul of a decedent. It is the proper r ...
, taken from its incipit
The incipit () of a text is the first few words of the text, employed as an identifying label. In a musical composition, an incipit is an initial sequence of notes, having the same purpose. The word ''incipit'' comes from Latin and means "it beg ...
, a quote from the Vulgate
The Vulgate (; also called (Bible in common tongue), ) is a late-4th-century Latin translation of the Bible.
The Vulgate is largely the work of Jerome who, in 382, had been commissioned by Pope Damasus I to revise the Gospels u ...
's Psalm 116
Psalm 116 is the 116th psalm of the Book of Psalms, beginning in English in the King James Version: "I love the LORD, because he hath heard my voice and my supplications". It is part of the Egyptian Hallel sequence in the Book of Psalms.
In the ...
:9, ''placēbō Dominō in regiōne vīvōrum,'' " shall please the Lord in the land of the living." From that, a ''singer of placebo'' became associated with someone who falsely claimed a connection to the deceased to get a share of the funeral meal, and hence a flatterer, and so a deceptive act to please.
Definitions
The American Society of Pain Management Nursing defines a placebo as "any sham medication or procedure designed to be void of any known therapeutic value".[
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 reversion to the mean, and reversion to mediocrity) is the fact that if one sample of a random variable is extreme, the next sampling of the same random variable is likely to be closer to it ...
), 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 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 "blood pressure" r ...
) or ''subjective'' (e.g. a lowered perception of pain).
Effects
Placebos can improve patient-reported outcomes such as pain
Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...
and nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
. This effect is unpredictable and hard to measure, even in the best conducted trials.[ For example, if used to treat ]insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
, placebos can cause patients to perceive that they are sleeping better, but do not improve objective measurements of sleep onset latency
In sleep science, sleep onset latency (SOL) is the length of time that it takes to accomplish the transition from full wakefulness to sleep, normally to the lightest of the non-REM sleep stages.
Sleep latency studies
Pioneering Stanford Universi ...
. A 2001 Cochrane Collaboration
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
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.
By contrast, placebos do not appear to affect the actual diseases, or outcomes that are not dependent on a patient's perception.[ One exception to the latter is ]Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
, where recent research has linked placebo interventions to improved motor functions.
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). 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 incl ...
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
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 Eviden ...
and Peter C. Gøtzsche
Peter Christian Gøtzsche (born 26 November 1949) is a Danish physician, medical researcher, and former leader of the Nordic Cochrane Center at Rigshospitalet in Copenhagen, Denmark.
He is a co-founder of the Cochrane Collaboration and has writ ...
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."[ Hróbjartsson and Gøtzsche concluded that their study "did not find that placebo interventions have important clinical effects in general".][ However, in a study in 2010, patients given open-label placebo in the context of a supportive patient-practitioner relationship and a persuasive rationale had clinically meaningful symptom improvement that was significantly better than a no-treatment control group with matched patient-provider interaction.]
Jeremy Howick
Jeremy Howick is a Canadian-born, British residing clinical epidemiologist and philosopher of science. He researches evidence-based medicine, clinical empathy and the philosophy of medicine, including the use of placebos in clinical practice a ...
has argued that combining so many varied studies to produce a single average might obscure that "some placebos for some things could be quite effective." To demonstrate this, he participated in a systematic review comparing active treatments and placebos using a similar method, which generated a conclusion that there is "no difference between treatment and placebo effects".
Factors influencing the power of the placebo effect
A review published in ''JAMA Psychiatry'' 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 damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...
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.
Children
A child ( : children) is a human being between the stages of birth and puberty, or between the developmental period of infancy and puberty. The legal definition of ''child'' generally refers to a minor, otherwise known as a person younger ...
seem to have a greater response than adults
An adult is a human or other animal that has reached full growth. In human context, the term ''adult'' has meanings associated with social and legal concepts. In contrast to a "minor", a legal adult is a person who has attained the age of majori ...
to placebos.
The administration of the placebos can determine the placebo effect strength. Studies have found that taking more pills would strengthen the effect. Besides, 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''. A 2017 meta-analysis based on 5 studies found some evidence that open-label placebos may have positive effects in comparison to no treatment, which may open new avenues for treatments, but noted the trials 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 would be more effectual.
Symptoms and conditions
A 2010 Cochrane Collaboration review suggests that placebo effects are apparent only in subjective, continuous measures, and in the treatment of pain and related conditions.
Pain
Placebos are believed to be capable of altering a person's perception of pain. "A person might reinterpret a sharp pain as uncomfortable tingling."
One way in which the magnitude of placebo analgesia 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.
Depression
In 2008, a controversial meta-analysis led by psychologist Irving Kirsch
Irving Kirsch (born March 7, 1943) is an American psychologist and academic. He is the Associate Director of the Program in Placebo Studies and a lecturer in medicine at the Harvard Medical School and Beth Israel Deaconess Medical Center. He is ...
, analyzing data from the FDA, concluded that 82% of the response to antidepressants was accounted for by placebos. However, there are serious 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 discovered 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.
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 branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
''nocebo'' = "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, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
associated with real treatment. Failure to minimise nocebo side-effects
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
in clinical trials and clinical practice raises a number of recently explored ethical issues.
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. These symptoms can include hot flashes, vaginal ...
for menopause
Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...
. Women had been on placebo for an average of 5.7 years. Moderate or severe withdrawal
Withdrawal means "an act of taking out" and may refer to:
* Anchoresis (withdrawal from the world for religious or ethical reasons)
* ''Coitus interruptus'' (the withdrawal method)
* Drug withdrawal
* Social withdrawal
* Taking of money from a ban ...
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 a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of 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, fi, Helsingin julistus, sv, Helsingforsdeklarationen) is a set of ethical principles regarding human experimentation developed originally in 1964 for the medical community by the World Medical Association (WMA) ...
. 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, believe that a substance that causes symptoms of a dis ...
, 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 me ...
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, alleged ...
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 is any practice that aims to achieve the healing effects of medicine despite lacking biological plausibility, testability, repeatability, or evidence from clinical trials. Complementary medicine (CM), complementary and alt ...
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
Fabrizio Benedetti is professor of physiology and neuroscience at the University of Turin Medical School in Turin, Italy and a researcher in the field of placebo studies. He is known for his research into the placebo and nocebo effects.
Placebo ...
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 the placebo "effect" remains unknown. An open-label study in 2010 showed that it had an effect even when patients were clearly told that the placebo pill they were receiving was an inactive (i.e., "inert") substance like a sugar pill that contained no medication. These results challenge "the conventional wisdom" that placebo effects require "intentional ignorance." A placebo presented as a stimulant
Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
may trigger an effect on heart rhythm
The cardiac conduction system (CCS) (also called the electrical conduction system of the heart) transmits the signals generated by the sinoatrial node – the heart's pacemaker, to cause the heart muscle to contract, and pump blood through the ...
and blood pressure
Blood pressure (BP) is the pressure of 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 "blood pressure" r ...
, but when administered as a depressant
A depressant, or central depressant, is a drug that lowers neurotransmission levels, which is to depress or reduce arousal or stimulation, in various areas of the brain. Depressants are also colloquially referred to as downers as they lower the ...
, the opposite effect.
Psychology
In psychology, the two main hypotheses of the placebo effect are expectancy theory and classical conditioning
Classical conditioning (also known as Pavlovian or respondent conditioning) is a behavioral procedure in which a biologically potent stimulus (e.g. food) is paired with a previously neutral stimulus (e.g. a triangle). It also refers to the learni ...
.
In 1985, Irving Kirsch
Irving Kirsch (born March 7, 1943) is an American psychologist and academic. He is the Associate Director of the Program in Placebo Studies and a lecturer in medicine at the Harvard Medical School and Beth Israel Deaconess Medical Center. He is ...
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 the reason for which humans and other animals initiate, continue, or terminate a behavior at a given time. Motivational states are commonly understood as forces acting within the agent that create a disposition to engage in goal-dire ...
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
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 ...
suggests links to the activation, and increased functional correlation between this activation, in the anterior cingulate
In the human brain, 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 i ...
, prefrontal, orbitofrontal
The orbitofrontal cortex (OFC) is a prefrontal cortex region in the frontal lobes of the brain which is involved in the cognitive process of decision-making. In non-human primates it consists of the association cortex areas Brodmann area 11, 12 ...
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 hypotha ...
, amygdala
The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...
, the brainstem periaqueductal gray matter
The periaqueductal gray (PAG, also known as the central gray) is a brain region that plays a critical role in Autonomic nervous system, autonomic function, Motivation, motivated behavior and behavioural responses to threatening stimuli. PAG is a ...
, and the spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
.
It has been known that placebo analgesia depends upon the release in the brain of endogenous opioids
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
since 1978. 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 (''aka'' saccharine, Sodium sacchari) is an artificial sweetener with effectively no nutritional value. It is about 550 times as sweet as sucrose but has a bitter or metallic aftertaste, especially at high concentrations. Saccharin is u ...
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 ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
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 long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
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
In statistics, regression toward the mean (also called reversion to the mean, and reversion to mediocrity) is the fact that if one sample of a random variable is extreme, the next sampling of the same random variable is likely to be closer to it ...
(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 worked best while they were still new:
Placebos have featured in medical use until well into the twentieth century. In 1955 Henry K. Beecher
Henry Knowles Beecher (February 4, 1904 – July 25, 1976) was a pioneering American anesthesiologist, medical ethicist, and investigator of the placebo effect at Harvard Medical School.
An article by Beecher's in 1966 on unethical medical exp ...
published an influential paper entitled ''The Powerful Placebo'' which proposed the idea that placebo effects were clinically important. Subsequent re-analysis of his materials, however, found in them no evidence of any "placebo effect".
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
* 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 therap ...
* List of topics characterized as pseudoscience
This is a list of topics that have, either currently or in the past, been characterized as pseudoscience by academics or researchers. Detailed discussion of these topics may be found on their main pages. These characterizations were made in the ...
* 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 o ...
* Self-fulfilling prophecy
A self-fulfilling prophecy is a prediction that comes true at least in part as a result of a person's or group of persons' belief or expectation that said prediction would come true. This suggests that people's beliefs influence their actions. ...
* Nocebo
A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the treatment to have a more negative effect than it otherwise would have. For example, when a patient anticipates a side effect of a medicatio ...
* 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 Paris F ...
Further reading
*
*
*
*
References
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. It was formed out of the 1996 merger of Beth Israel Hospital (founded in 1916) and New England Deaconess Hospital (founded ...
and Harvard Medical School
Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...
)
{{Authority control
Clinical research
Deception
Ethically disputed medical practices
Mind–body interventions