The '''lessebo effect''' is a phenomenon in [[psychology]] and [[medicine]] in which a person in a [[blinded experiment|blinded]] [[clinical trial]] knows that they might receive [[placebo]] due to the existence of a placebo [[control group]] in the trial and this results in the person experiencing diminished [[placebo effect]]s (positive expectations) and therapeutic improvement.<ref name="Mestre2020">{{cite journal | vauthors = A Mestre T | title = Nocebo and lessebo effects | journal = Int Rev Neurobiol | volume = 153 | issue = | pages = 121–146 | date = 2020 | pmid = 32563285 | doi = 10.1016/bs.irn.2020.04.005 | url = }}</ref><ref name="SinyorLevittCheung2010">{{cite journal | vauthors = Sinyor M, Levitt AJ, Cheung AH, Schaffer A, Kiss A, Dowlati Y, Lanctôt KL | title = Does inclusion of a placebo arm influence response to active antidepressant treatment in randomized controlled trials? Results from pooled and meta-analyses | journal = J Clin Psychiatry | volume = 71 | issue = 3 | pages = 270–279 | date = March 2010 | pmid = 20122371 | doi = 10.4088/JCP.08r04516blu | url = }}</ref> It has been described in several contexts including clinical trials of treatment for [[depression (mood)|depression]],<ref name="HenkelCasaultaSeemüller2012">{{cite journal | vauthors = Henkel V, Casaulta F, Seemüller F, Krähenbühl S, Obermeier M, Hüsler J, Möller HJ | title = Study design features affecting outcome in antidepressant trials | journal = J Affect Disord | volume = 141 | issue = 2-3 | pages = 160–167 | date = December 2012 | pmid = 22658811 | doi = 10.1016/j.jad.2012.03.021 | url = }}</ref><ref name="Papakostas2009">{{cite journal | vauthors = Papakostas GI, Fava M | title = Does the probability of receiving placebo influence clinical trial outcome? A meta-regression of double-blind, randomized clinical trials in MDD | journal = Eur Neuropsychopharmacol | volume = 19 | issue = 1 | pages = 34–40 | date = January 2009 | pmid = 18823760 | doi = 10.1016/j.euroneuro.2008.08.009 | url = }}</ref><ref name="RutherfordSneedRoose2009">{{cite journal | vauthors = Rutherford BR, Sneed JR, Roose SP | title = Does study design influence outcome?. The effects of placebo control and treatment duration in antidepressant trials | journal = Psychother Psychosom | volume = 78 | issue = 3 | pages = 172–181 | date = 2009 | pmid = 19321970 | pmc = 3785090 | doi = 10.1159/000209348 | url = }}</ref> [[schizophrenia]],<ref name="WoodsGuerguievaBaker2005">{{cite journal | vauthors = Woods SW, Gueorguieva RV, Baker CB, Makuch RW | title = Control group bias in randomized atypical antipsychotic medication trials for schizophrenia | journal = Arch Gen Psychiatry | volume = 62 | issue = 9 | pages = 961–970 | date = September 2005 | pmid = 16143728 | doi = 10.1001/archpsyc.62.9.961 | url = }}</ref> [[Parkinson's disease]],<ref name="MestreShahMarras2014">{{cite journal | vauthors = Mestre TA, Shah P, Marras C, Tomlinson G, Lang AE | title = Another face of placebo: the lessebo effect in Parkinson disease: meta-analyses | journal = Neurology | volume = 82 | issue = 16 | pages = 1402–1409 | date = April 2014 | pmid = 24658930 | pmc = 4001195 | doi = 10.1212/WNL.0000000000000340 | url = }}</ref><ref name="MestreLangOkun2016">{{cite journal | vauthors = Mestre TA, Lang AE, Okun MS | title = Factors influencing the outcome of deep brain stimulation: Placebo, nocebo, lessebo, and lesion effects | journal = Mov Disord | volume = 31 | issue = 3 | pages = 290–296 | date = March 2016 | pmid = 26952118 | doi = 10.1002/mds.26500 | url = }}</ref><ref name="MestreMcDermottLobo2023">{{cite journal | vauthors = Mestre TA, McDermott MP, Lobo R, Ferreira JJ, Lang AE | title = The Lessebo Effect in Disease Modification Trials in Parkinson's Disease | journal = Mov Disord | volume = 38 | issue = 7 | pages = 1346–1350 | date = July 2023 | pmid = 37093589 | doi = 10.1002/mds.29414 | url = | doi-access = free }}</ref> and [[rheumatoid arthritis]].<ref name="SungLee2023">{{cite journal | vauthors = Sung YK, Lee YH | title = The lessebo effect in randomized controlled trials of rituximab in patients with rheumatoid arthritis: a meta-analysis | journal = Z Rheumatol | volume = 82 | issue = Suppl 1 | pages = 44–50 | date = January 2023 | pmid = 34761312 | doi = 10.1007/s00393-021-01126-9 | url = }}</ref><ref name="Mestre2020" /> The phenomenon was first named the "lessebo effect" by Mark Sinyor and colleagues in 2010.<ref name="Mestre2020" /><ref name="SinyorLevittCheung2010" /> They showed in a [[meta-analysis]] that [[antidepressant]] and placebo [[response rate (medicine)|response rate]]s are influenced by the presence of a placebo arm and by the number of treatment arms (and thus likelihood of receiving placebo) in trials.<ref name="SinyorLevittCheung2010" /> A closely related but slightly distinct concept is the [[inverse placebo effect]],<ref name="AnsariElliottHolmes2026">{{cite journal | vauthors = Ansari M, Elliott SI, Holmes SE, Sanacora G | title = Placebo Effects in the Treatment of Depression-Implications for the Psychedelic Renaissance | journal = Neurol Clin | volume = 44 | issue = 1 | pages = 63–75 | date = February 2026 | pmid = 41232997 | doi = 10.1016/j.ncl.2025.08.009 | url = }}</ref><ref name="WilliamsBarnettSzigeti2026">{{cite journal | vauthors = Williams ZJ, Barnett H, Szigeti B | title = Psychedelic Therapy vs Antidepressants for the Treatment of Depression Under Equal Unblinding Conditions: A Systematic Review and Meta-Analysis | journal = JAMA Psychiatry | volume = | issue = | pages = | date = March 2026 | pmid = 41848744 | doi = 10.1001/jamapsychiatry.2025.4809 | url = }}</ref><ref name="Hamzelou2026">{{cite web | last=Hamzelou | first=Jessica | title=Mind-altering substances are (still) falling short in clinical trials | website=MIT Technology Review | date=20 March 2026 | url=https://www.technologyreview.com/2026/03/20/1134419/psychedelics-overhyped-psilocybin-depression-placebo/ | access-date=20 March 2026}}</ref> which the lessebo effect has sometimes been inappropriately confused and conflated with.<ref name="HunekeFusettoVeronesi2025">{{cite journal | vauthors = Huneke NT, Fusetto Veronesi G, Garner M, Baldwin DS, Cortese S | title = Expectancy Effects, Failure of Blinding Integrity, and Placebo Response in Trials of Treatments for Psychiatric Disorders: A Narrative Review | journal = JAMA Psychiatry | volume = 82 | issue = 5 | pages = 531–538 | date = May 2025 | pmid = 40072447 | doi = 10.1001/jamapsychiatry.2025.0085 | url = }}</ref><ref name="MeshkatLinSousa-Ho2026">{{cite journal | vauthors = Meshkat S, Lin Q, Sousa-Ho R, Demchenko I, Zeifman RJ, Fang H, Reichelt AC, Zhang Y, Burback L, Winkler O, Greenshaw A, Monson CM, Vermetten E, Jetly R, Lou W, Husain MI, Burke MJ, Bhat V | title = Magnitude of Response in Treatment and Control Groups within Psychedelic Trials for Psychiatric Disorders: A Meta-Analysis | journal = Eur Psychiatry | volume = | issue = | pages = 1–35 | date = February 2026 | pmid = 41705428 | doi = 10.1192/j.eurpsy.2026.10168 | url = | quote = A further methodological consideration is that psychedelic trials may be especially susceptible to lessebo effects attenuated improvement when participants infer assignment to placebo or a sub-therapeutic condition, particularly in settings characterized by strong prior expectations and imperfect masking [48,49].| doi-access = free }}</ref>
==See also== * [[Inverse placebo effect]] * [[Amplified placebo effect]]
==References== {{Reflist}}
[[Category:Clinical research]] [[Category:Medicinal chemistry]]