Journal of psychoactive drugsJun 13, 2020

Psychedelic-Assisted Therapy Compared to Placebo: A Combined Analysis of Clinical Trials

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 25, 2026

Abstract

A significant mean effect size of 1.21 was observed in randomized trials of psychedelic-assisted therapy for mental health conditions.

Psychedelic-assisted therapy has shown efficacy for conditions like post-traumatic stress disorder and anxiety associated with life-threatening illness.
Nine placebo-controlled clinical trials were analyzed, focusing on substances such as psilocybin, LSD, ayahuasca, and MDMA.
Effects of the therapy were generally maintained at follow-up in studies with ongoing placebo control.
The observed effect size is larger than typical effects found in traditional psychopharmacological or psychotherapy trials.
High study quality was noted, but improvements in trial conduct and reporting were identified.
There is a need for larger and more diverse trials to further explore the effects and their longevity.

Simplified

After a two-decade hiatus in which research on psychedelics was essentially halted, placebo-controlled clinical trials of psychedelic-assisted therapy for mental health conditions have begun to be published. We identified nine randomized, placebo-controlled clinical trials of psychedelic-assisted therapy published since 1994. Studies examined psilocybin, LSD (lysergic acid diethylamide), ayahuasca (which contains a combination of N,N-dimethyltryptamine and harmala monoamine oxidase inhibitor alkaloids), and MDMA (3,4-methylenedioxymethamphetamine). We compared the standardized mean difference between the experimental and placebo control group at the primary endpoint. Results indicated a significant mean between-groups effect size of 1.21 (Hedges), which is larger than the typical effect size found in trials of psychopharmacological or psychotherapy interventions. For the three studies that maintained a placebo control through a follow-up assessment, effects were generally maintained at follow-up. Overall, analyses support the efficacy of psychedelic-assisted therapy across four mental health conditions - post-traumatic stress disorder, anxiety/depression associated with a life-threatening illness, unipolar depression, and social anxiety among autistic adults. While study quality was high, we identify several areas for improvement regarding the conduct and reporting of trials. Larger trials with more diverse samples are needed to examine possible moderators and mediators of effects, and to establish whether effects are maintained over time. g

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Declaration of Interest Statement. AKD and RL are members of the board of directors at Source Research Foundation, a non-profit educational grant-making organization providing financial assistance to students who conduct research related to psychedelics. This organization had no input into the present study. The other authors have no conflicts of interest to declare.

PubMed

Psychedelic-Assisted Therapy Compared to Placebo: A Combined Analysis of Clinical Trials

Abstract

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Competing interests

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Abstract

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