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{{short description|Substance or treatment of no therapeutic value}}
{{cs1 config|name-list-style=vanc}}
{{other uses|Placebo (disambiguation)}}
[[File:Cebocap.jpg|thumb|Placebos are typically inert tablets, such as sugar pills.]]
A '''placebo''' ({{IPAc-en|p|l|ə|ˈ|s|iː|b|oʊ}} {{respell|plə|SEE|boh}})
Placebos are used in [[Randomized controlled trial|randomized clinical trials]] to test the efficacy of [[Drug|medical treatments]]. In a [[Placebo-controlled study|placebo-controlled]] [[clinical trial]],
The idea of a placebo effect was discussed in 18th century psychology,<ref>Schwarz, K. A., & Pfister, R.: ''Scientific psychology in the 18th century: a historical rediscovery.'' In: ''Perspectives on Psychological Science'', Nr. 11, pp. 399–407.</ref> but became more prominent in the 20th century. Modern studies find that placebos can affect some outcomes such as [[pain]] and [[nausea]], but otherwise do not generally have important clinical effects.<ref name="CochraneHrob2010" /> Improvements that patients experience after being treated with a placebo can also be due to unrelated factors, such as [[regression to the mean]] (a statistical effect where an unusually high or low measurement is likely to be followed by a less extreme one).<ref name="acs" /> 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]].<ref name="Newman">{{cite book |last=Newman |first=David H. |title=Hippocrates' Shadow |publisher=Scribner |year=2008 |isbn=978-1-4165-5153-9 |pages=134–159}}</ref>
Placebos are also popular because they can sometimes produce relief through psychological mechanisms (phenomenon known as "placebo effect"). They can affect how patients perceive their condition and encourage the body's chemical processes for relieving pain<ref name="acs" /> and a few other symptoms,<ref name="quattrone-barbagallo" /> but have no impact on the [[disease]] itself.<ref name="CochraneHrob2010" /><ref name="acs" />▼
▲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<ref name="acs">{{cite web |date=10 April 2015 |title=Placebo Effect |url=https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/placebo-effect.html |url-status=live |archive-url=https://web.archive.org/web/20200522232756/https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/placebo-effect.html |archive-date=2020-05-22 |access-date=2021-06-27 |publisher=American Cancer Society}}</ref> and a few other symptoms,<ref name="quattrone-barbagallo" /> but have no impact on the [[disease]] itself.<ref name="CochraneHrob2010" /><ref name="acs" />
==Etymology==
==Definitions==
The definition of
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.<ref name=chaplin>{{cite journal |year=2006 | vauthors=Chaplin S |journal=Prescriber | volume=17 | issue=5 |title=The placebo response: an important part of treatment |doi=10.1002/psb.344 |pages=16–22 | s2cid=72626022 |doi-access=free }}</ref> 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]]), and errors in the clinical trial records, which can make it appear that a change has happened when nothing has changed.<ref>{{Cite journal|last1=Kaptchuk|first1=Ted J|last2=Hemond|first2=Christopher C|last3=Miller|first3=Franklin G|date=2020-07-20|title=Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice|journal=BMJ|volume=370|language=en|pages=m1668|doi=10.1136/bmj.m1668|pmid=32690477|s2cid=220633770|issn=1756-1833|doi-access=free}}</ref> It is also part of the recorded response to any active medical intervention.<ref name=eccles>{{cite journal | vauthors = Eccles R | title = The powerful placebo in cough studies? | journal = Pulmonary Pharmacology & Therapeutics | volume = 15 | issue = 3 | pages = 303–308 | year = 2002 | pmid = 12099783 | doi = 10.1006/pupt.2002.0364 }}</ref>
Measurable placebo effects may be either ''objective'' (e.g. lowered [[blood pressure]]) or ''subjective'' (e.g. a lowered perception of pain).<ref name="aspmn">{{cite journal |last1=Ashar |first1=Yoni K. |last2=Chang |first2=Luke J. |last3=Wager |first3=Tor D. |year=2017 |title=Brain Mechanisms of the Placebo Effect: An Affective Appraisal Account
==Effects==
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{{further|Alternative medicine#Perceived mechanism of effect}}
Placebos can improve patient-reported outcomes such as [[pain]] and [[nausea]].<ref name=CochraneHrob2010>{{cite journal | vauthors = Hróbjartsson A, Gøtzsche PC | title = Placebo interventions for all clinical conditions | journal = The Cochrane Database of Systematic Reviews | volume = 106 | issue = 1 | pages = CD003974 | date = January 2010 | pmid = 20091554 | doi = 10.1002/14651858.CD003974.pub3 | pmc = 7156905 | editor1-last = Hróbjartsson | editor1-first = Asbjørn | url = http://nordic.cochrane.org/sites/nordic.cochrane.org/files/public/uploads/ResearchHighlights/Placebo%20interventions%20for%20all%20clinical%20conditions%20(Cochrane%20review).pdf | access-date = 2018-06-25 | archive-date = 2019-04-02 | archive-url = https://web.archive.org/web/20190402005647/https://nordic.cochrane.org/sites/nordic.cochrane.org/files/public/uploads/ResearchHighlights/Placebo%20interventions%20for%20all%20clinical%20conditions%20(Cochrane%20review).pdf | url-status = dead }}</ref><ref>{{cite journal |last1=Benedetti |first1=Fabrizio |title=Mechanisms of Placebo and Placebo-Related Effects Across Diseases and Treatments |journal=Annual Review of Pharmacology and Toxicology |date=1 February 2008 |volume=48 |issue=1 |pages=33–60 |doi=10.1146/annurev.pharmtox.48.113006.094711 |pmid=17666008 |url=https://doi.org/10.1146/annurev.pharmtox.48.113006.094711 |access-date=17 March 2022 |issn=0362-1642}}</ref>
Placebos are believed to be capable of altering a person's perception of pain. According to the American Cancer Society, "A person might reinterpret a sharp pain as uncomfortable tingling."<ref name="acs" />
Measuring the extent of the placebo effect is difficult due to confounding factors.<ref name=Hrob2004>{{cite journal | vauthors = Hróbjartsson A, Gøtzsche PC | author-link1 = Asbjørn Hróbjartsson | author-link2 = Peter C. Gøtzsche | title = Is the placebo powerless? Update of a systematic review with 52 new randomized trials comparing placebo with no treatment | journal = Journal of Internal Medicine | volume = 256 | issue = 2 | pages = 91–100 | date = August 2004 | pmid = 15257721 | doi = 10.1111/j.1365-2796.2004.01355.x | s2cid = 21244034 | doi-access = free }} Gøtzsche's biographical article has further references related to this work.</ref> 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),<ref name="Kienle & Kiene">{{cite journal | vauthors = Kienle GS, Kiene H | title = The powerful placebo effect: fact or fiction? | journal = Journal of Clinical Epidemiology | volume = 50 | issue = 12 | pages = 1311–8 | date = December 1997 | pmid = 9449934 | doi = 10.1016/s0895-4356(97)00203-5 }}</ref><ref name="How much?">{{cite journal | vauthors = McDonald CJ, Mazzuca SA, McCabe GP | title = How much of the placebo 'effect' is really statistical regression? | journal = Statistics in Medicine | volume = 2 | issue = 4 | pages = 417–27 | year = 1983 | pmid = 6369471 | doi = 10.1002/sim.4780020401 }}</ref><ref name=RTM>{{cite journal | vauthors = Barnett AG, van der Pols JC, Dobson AJ | title = Regression to the mean: what it is and how to deal with it | journal = International Journal of Epidemiology | volume = 34 | issue = 1 | pages = 215–20 | date = February 2005 | pmid = 15333621 | doi = 10.1093/ije/dyh299 | doi-access = free }}</ref> 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]], [[observer bias]] and other flaws in trial methodology, as a trial comparing placebo treatment and no treatment will not be a [[blinded experiment]].<ref name=CochraneHrob2010/><ref name="Kienle & Kiene"/> In their 2010 meta-analysis of the placebo effect,
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.<ref>{{cite journal |
===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.<ref>{{cite journal | vauthors = Rutherford BR, Pott E, Tandler JM, [[Melanie Wall|Wall MM]], Roose SP, Lieberman JA | title = Placebo response in antipsychotic clinical trials: a meta-analysis | journal = JAMA Psychiatry | volume = 71 | issue = 12 | pages = 1409–21 | date = December 2014 | pmid = 25321611 | pmc = 4256120 | doi = 10.1001/jamapsychiatry.2014.1319 }}</ref> Another analysis published in ''Pain'' in 2015 found that placebo responses had increased considerably in [[neuropathic pain]] 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.<ref>{{cite journal | vauthors = Tuttle AH, Tohyama S, Ramsay T, Kimmelman J, Schweinhardt P, Bennett GJ, Mogil JS | title = Increasing placebo responses over time in U.S. clinical trials of neuropathic pain | journal = Pain | volume = 156 | issue = 12 | pages = 2616–26 | date = December 2015 | pmid = 26307858 | doi = 10.1097/j.pain.0000000000000333 | s2cid = 23246031 }}
* {{lay source |template = cite magazine|vauthors = Dahl M |url= https://www.thecut.com/2015/10/placebo-effect-is-getting-stronger.html|title = The Placebo Effect Is Getting Stronger — But Only in the U.S.|date = October 9, 2015 |website = The Cut}}</ref>
[[childhood|Children]] seem to have a greater response than [[adults]] to placebos.<ref>{{cite journal | vauthors = Rheims S, Cucherat M, Arzimanoglou A, Ryvlin P | title = Greater response to placebo in children than in adults: a systematic review and meta-analysis in drug-resistant partial epilepsy | journal = PLOS Medicine | volume = 5 | issue = 8 | pages = e166 | date = August 2008 | pmid = 18700812 | pmc = 2504483 | doi = 10.1371/journal.pmed.0050166 | editor1-last = Klassen | editor1-first = Terry | doi-access = free }}</ref>
The administration of the placebos can determine the placebo effect strength. Studies have found that taking more pills would strengthen the effect.
Some studies have investigated the use of placebos where the patient is fully aware that the treatment is inert, known as an ''[[Open-label trial|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,<ref name="Blease2019">{{cite journal |last1=Blease |first1=CR |last2=Bernstein |first2=MH |last3=Locher |first3=C |date=26 June 2019 |title=Open-label placebo clinical trials: is it the rationale, the interaction or the pill? |journal=BMJ Evidence-Based Medicine |
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
In the 2022 book ''Epigenetics and Anticipation''
===
In 2008, a
▲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.<ref>{{cite journal | vauthors = Price DD, Finniss DG, Benedetti F | title = A comprehensive review of the placebo effect: recent advances and current thought | journal = Annual Review of Psychology | volume = 59 | issue = 1 | pages = 565–90 | date = 2008 | pmid = 17550344 | doi = 10.1146/annurev.psych.59.113006.095941 }}</ref>
▲In 2008, a controversial meta-analysis led by psychologist [[Irving Kirsch]], analyzing data from the FDA, concluded that 82% of the response to antidepressants was accounted for by placebos.<ref>{{cite journal | vauthors = Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT | title = Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration | journal = PLOS Medicine | volume = 5 | issue = 2 | pages = e45 | date = February 2008 | pmid = 18303940 | pmc = 2253608 | doi = 10.1371/journal.pmed.0050045 | doi-access = free }}</ref> 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]].<ref name="TurnerRosenthal2008">{{cite journal | vauthors = Turner EH, Rosenthal R | title = Efficacy of antidepressants | journal = BMJ | volume = 336 | issue = 7643 | pages = 516–7 | date = March 2008 | pmid = 18319297 | pmc = 2265347 | doi = 10.1136/bmj.39510.531597.80 }}</ref> 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.<ref name="FountoulakisMöller2010">{{cite journal | vauthors = Fountoulakis KN, Möller HJ | title = Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data | journal = The International Journal of Neuropsychopharmacology | volume = 14 | issue = 3 | pages = 405–12 | date = April 2011 | pmid = 20800012 | doi = 10.1017/S1461145710000957 | doi-access = free }}</ref>
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.<ref>{{cite journal | vauthors = Khan A, Redding N, Brown WA | title = The persistence of the placebo response in antidepressant clinical trials | journal = Journal of Psychiatric Research | volume = 42 | issue = 10 | pages = 791–6 | date = August 2008 | pmid = 18036616 | doi = 10.1016/j.jpsychires.2007.10.004 }}</ref>
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{{main|Nocebo}}
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]]
Another negative consequence is that placebos can cause [[Adverse effect (medicine)|side-effects]] associated with real treatment.<ref>{{cite journal |vauthors=Shapiro AK, Chassan J, Morris LA, Frick R |year=1974 |title=Placebo induced side effects |journal=Journal of Operational Psychiatry |volume=6 |pages=43–6 |url=http://psycnet.apa.org/?fa=main.doiLanding&uid=1977-04006-001
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 (menopause)|hormone replacement therapy]] for [[menopause]]. Women had been on placebo for an average of 5.7 years. Moderate or severe [[Drug withdrawal|withdrawal]] symptoms were reported by 4.8% of those on placebo compared to 21.3% of those on hormone replacement.<ref>{{cite journal | vauthors = Ockene JK, Barad DH, Cochrane BB, Larson JC, Gass M, Wassertheil-Smoller S, Manson JE, Barnabei VM, Lane DS, Brzyski RG, Rosal MC, Wylie-Rosett J, Hays J | title = Symptom experience after discontinuing use of estrogen plus progestin | journal = JAMA | volume = 294 | issue = 2 | pages = 183–93 | date = July 2005 | pmid = 16014592 | doi = 10.1001/jama.294.2.183 | doi-access = free }}</ref>
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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]].
Some suggest that existing medical treatments should be used instead of placebos, to avoid having some patients not receive medicine during the trial.<ref name="michels">{{cite journal | vauthors = Michels KB | title = The placebo problem remains | journal = Archives of General Psychiatry | volume = 57 | issue = 4 | pages = 321–2 | date = April 2000 | pmid = 10768689 | doi = 10.1001/archpsyc.57.4.321 }}</ref>
===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.<ref>{{cite journal | vauthors = Asai A, Kadooka Y | title = Reexamination of the ethics of placebo use in clinical practice | journal = Bioethics | volume = 27 | issue = 4 | pages = 186–93 | date = May 2013 | pmid = 22296589 | doi = 10.1111/j.1467-8519.2011.01943.x | s2cid = 11300075 }}</ref> This view is shared by some on the grounds of [[Autonomy#Medicine|patient autonomy]].<ref>{{cite journal | vauthors = Chua SJ, Pitts M | title = The ethics of prescription of placebos to patients with major depressive disorder | journal = Chinese Medical Journal | volume = 128 | issue = 11 | pages = 1555–7 | date = June 2015 | pmid = 26021517 | doi = 10.4103/0366-6999.157699 | pmc = 4733778 | doi-access = free }}</ref> There are also concerns that legitimate doctors and pharmacists could open themselves up to charges of fraud or malpractice by using a placebo.<ref>{{cite journal|last1=Malani|first1=Anup
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.<ref>{{Cite journal|last1=Nitzan|first1=Uriel|last2=Lichtenberg|first2=Pesach|date=2004-10-23|title=Questionnaire survey on use of placebo|journal=BMJ: British Medical Journal|volume=329|issue=7472|pages=944–946|doi=10.1136/bmj.38236.646678.55|issn=0959-8138|pmid=15377572|pmc=524103|doi-access=free}}</ref> 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{{Spaces}}...the use of the placebo for 'diagnosis' of whether or not pain is real is misguided."<ref name="Spiegel">{{cite journal|vauthors=Spiegel D|date=October 2004|title=Placebos in practice|journal=BMJ|volume=329|issue=7472|pages=927–8|doi=10.1136/bmj.329.7472.927|pmc=524090|pmid=15499085}}</ref> 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.<ref name=kane>[http://www.medscape.com/viewarticle/731485_7 Doctors Struggle With Tougher-Than-Ever Dilemmas: Other Ethical Issues] Author: Leslie Kane. 11/11/2010</ref>
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In his 2008 book ''[[Bad Science (Goldacre book)|Bad Science]]'', [[Ben Goldacre]] argues that instead of deceiving patients with placebos, doctors should use the placebo effect to enhance effective medicines.<ref name="bad-science">{{cite book | first = Ben | last = Goldacre |title=Bad Science |publisher=Fourth Estate |year=2008| chapter=5: The Placebo Effect |isbn=978-0-00-724019-7}}</ref> [[Edzard Ernst]] has argued similarly that "As a good doctor you should be able to transmit a placebo effect through the compassion you show your patients."<ref>{{cite journal | title = Empathy and ethics: five minutes with Edzard Ernst | journal = The BMJ | volume = 360 | issue = 1 | pages = k309| date = January 2018 | pmid = 29371199| doi = 10.1136/bmj.k309 | last1 = Rimmer | first1 = Abi | s2cid = 3511158 }}</ref> In an opinion piece about homeopathy, Ernst argues that it is wrong to support [[alternative medicine]] on the basis that it can make patients feel better through the placebo effect.<ref name="Ernst-homeopathy"/> His concerns are that it is deceitful and that the placebo effect is unreliable.<ref name="Ernst-homeopathy">{{cite news|title=No to homeopathy placebo | newspaper=The Guardian|url=https://www.theguardian.com/commentisfree/2010/feb/22/science-homeopathy-clinical-trials|date=22 February 2010|access-date=29 April 2019}}</ref> Goldacre also concludes that the placebo effect does not justify alternative medicine, arguing that unscientific medicine could lead to patients not receiving prevention advice.<ref name="bad-science"/>
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.<ref name="Benedetti">{{cite journal |last1=Benedetti |first1=Fabrizio |title=The science of placebos is fuelling quackery |journal=Knowable Magazine |date=3 March 2022 |doi=10.1146/knowable-030222-3 |s2cid=247265071 |url=https://knowablemagazine.org/article/society/2022/science-placebos-fuelling-quackery |access-date=17 March 2022|doi-access=free }}</ref>
==Mechanisms==
The mechanism for how placebos could have effects is uncertain.
===Psychology===
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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.<ref>{{cite journal | vauthors = Kirsch I |year=1985|title=Response expectancy as a determinant of experience and behavior|journal=American Psychologist|volume=40|issue=11|pages=1189–1202|doi=10.1037/0003-066X.40.11.1189}}</ref> 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.<ref>{{cite journal | vauthors = Voudouris NJ, Peck CL, Coleman G | title = Conditioned response models of placebo phenomena: further support | journal = Pain | volume = 38 | issue = 1 | pages = 109–16 | date = July 1989 | pmid = 2780058 | doi = 10.1016/0304-3959(89)90080-8 | s2cid = 40356035 }}</ref> Both conditioning and expectations play a role in placebo effect,<ref name="podd">{{cite journal | vauthors = Stewart-Williams S, Podd J | title = The placebo effect: dissolving the expectancy versus conditioning debate | journal = Psychological Bulletin | volume = 130 | issue = 2 | pages = 324–40 | date = March 2004 | pmid = 14979775 | doi = 10.1037/0033-2909.130.2.324 | s2cid = 10297875 }}</ref> and make different kinds of contributions. Conditioning has a longer-lasting effect,<ref>{{cite journal | vauthors = Klinger R, Soost S, Flor H, Worm M | title = Classical conditioning and expectancy in placebo hypoalgesia: a randomized controlled study in patients with atopic dermatitis and persons with healthy skin | journal = Pain | volume = 128 | issue = 1–2 | pages = 31–9 | date = March 2007 | pmid = 17030095 | doi = 10.1016/j.pain.2006.08.025 | s2cid = 27747260 }}</ref> and can affect earlier stages of information processing.<ref name="Colloca et al 2008">{{cite journal | vauthors = Colloca L, Tinazzi M, Recchia S, Le Pera D, Fiaschi A, Benedetti F, Valeriani M | title = Learning potentiates neurophysiological and behavioral placebo analgesic responses | journal = Pain | volume = 139 | issue = 2 | pages = 306–14 | date = October 2008 | pmid = 18538928 | doi = 10.1016/j.pain.2008.04.021 | s2cid = 27342664 }}</ref> Those who think a treatment will work display a stronger placebo effect than those who do not, as evidenced by a study of acupuncture.<ref>{{cite journal | vauthors = Linde K, Witt CM, Streng A, Weidenhammer W, Wagenpfeil S, Brinkhaus B, Willich SN, Melchart D | title = The impact of patient expectations on outcomes in four randomized controlled trials of acupuncture in patients with chronic pain | journal = Pain | volume = 128 | issue = 3 | pages = 264–71 | date = April 2007 | pmid = 17257756 | doi = 10.1016/j.pain.2006.12.006 | s2cid = 25561695 }}</ref>
Additionally, [[motivation]] 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.<ref name="Geers et al">{{cite journal | vauthors = Geers AL, Weiland PE, Kosbab K, Landry SJ, Helfer SG | title = Goal activation, expectations, and the placebo effect | journal = Journal of Personality and Social Psychology | volume = 89 | issue = 2 | pages = 143–59 | date = August 2005 | pmid = 16162050 | doi = 10.1037/0022-3514.89.2.143 }}</ref> 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.{{cn|date=November 2023}}
===Placebo analgesia===
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Since 1978, it has been known that placebo analgesia depends upon the release of [[endogenous opioids]] in the brain.<ref>{{cite journal | vauthors = Levine JD, Gordon NC, Fields HL | title = The mechanism of placebo analgesia | journal = Lancet | volume = 2 | issue = 8091 | pages = 654–7 | date = September 1978 | pmid = 80579 | doi = 10.1016/s0140-6736(78)92762-9 | s2cid = 45403755 }}</ref> Such analgesic placebos activation changes processing lower down in the brain by enhancing the descending inhibition through the periaqueductal gray on spinal [[Withdrawal reflex|nociceptive reflexes]], while the expectations of anti-analgesic nocebos acts in the opposite way to block this.<ref name="autogenerated2007"/>
Functional imaging upon placebo analgesia has been summarized as showing that the placebo response is "mediated by
===Brain and body===
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==Confounding factors==
Placebo-controlled studies, as well as studies of the placebo effect itself, often fail to adequately identify confounding factors.<ref name=acs/
* [[Regression to the mean]] (natural recovery or fluctuation of symptoms)
* Additional treatments
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}}
Placebos have featured in medical use until well into the twentieth century.<ref name=HistoricalOverview>{{cite journal | vauthors = de Craen AJ, Kaptchuk TJ, Tijssen JG, Kleijnen J | title = Placebos and placebo effects in medicine: historical overview | journal = Journal of the Royal Society of Medicine | volume = 92 | issue = 10 | pages = 511–515 | date = October 1999 | pmid = 10692902 | pmc = 1297390 | doi = 10.1177/014107689909201005}}</ref>
===Placebo-controlled studies===
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==See also==
*
* [[Homeopathy]]▼
* [[List of effects]]
* [[List of topics characterized as pseudoscience]]
* [[Nocebo]]
▲* [[Homeopathy]]
* [[Placebo button]]
* [[Royal Commission on Animal Magnetism]]
* [[Self-fulfilling prophecy]]<ref>{{Cite book|last=Benedetti|first=Fabrizio|title=Placebo Effects|date=2008-10-16|publisher=Oxford University Press|doi=10.1093/acprof:oso/9780199559121.001.0001|isbn=978-0-19-955912-1}}</ref>
==Further reading==▼
* {{Cite book|title=Placebos |first=Kathryn T |last=Hall |publisher=The MIT Press |year=2022 |isbn=978-0262544252 }}▼
* {{Cite book|title=Neurobiology of the placebo effect. Part I|last=Colloca|first=Luana|isbn=9780128143261|location=Cambridge, MA|oclc=1032303151|date=2018-04-20}}▼
* {{Cite book|title=Neurobiology of the placebo effect. Part II|last=Colloca|first=Luana|date=2018-08-23|isbn=9780128154175|edition=1st|location=Cambridge, MA, United States|oclc=1049800273}}▼
* {{Cite book|title=Suggestible You: The Curious Science of Your Brain's Ability to Deceive, Transform, and Heal |year=2016 |last=Erik |first=Vance |isbn=978-1426217890 |publisher=National Geographic}}▼
==References==
{{reflist}}
▲==Further reading==
▲* {{Cite book|title=Placebos |first=Kathryn T |last=Hall |publisher=The MIT Press |year=2022 |isbn=978-
▲* {{Cite book|title=Neurobiology of the placebo effect. Part I|last=Colloca|first=Luana|isbn=
▲* {{Cite book|title=Neurobiology of the placebo effect. Part II|last=Colloca|first=Luana|date=2018-08-23|isbn=
▲* {{Cite book|title=Suggestible You: The Curious Science of Your Brain's Ability to Deceive, Transform, and Heal |year=2016 |last=Erik |first=Vance |isbn=978-
==External links==
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[[Category:Clinical research]]
[[Category:Deception]]
[[Category:Mind–body interventions]]
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