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A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy

Jason B. Luoma, Christina Chwyl, Geoff J. Bathje, Alan K. Davis, Rafael Lancelotta

Journal of Psychoactive Drugs June 12, 2020 DOI: 10.1080/02791072.2020.1769878 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Randomized Placebo-controlled Peer reviewed
Interventions Psilocybin LSD ayahuasca MDMA
Topics Anxiety Psilocybin Psychedelic-assisted therapy
Keywords Placebo Hallucinogen Clinical trial Randomized controlled trial Clinical psychology
Citations 206
Key findings Psychedelic-assisted therapy shows a large effect size (Hedges g = 1.21) compared to placebo across four mental health conditions.

Abstract

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 g), 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.

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Comparable studies

Other systematic reviews and meta-analyses on psilocybin and psychedelic-assisted therapy, most cited first.

Study Year Design Participants
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... 2023 Systematic review with meta-analysis n = 14
Psilocybin-assisted therapy for depression: A systematic review and meta-analysis. Patients diagnosed with life-threatening illnesses or major depressive disorder 2023 Systematic review and meta-analysis n = 686
United States National Institutes of Health grant funding for psychedelic-assisted therapy clinical trials from 2006-2020. 2022 Systematic review
Safety and risk assessment of psychedelic psychotherapy: A meta-analysis and systematic review. Human subjects in studies of psychedelic-assisted psychotherapy 2024 Systematic review and meta-analysis n = 30
The Use of Psychedelics in the Treatment of Medical Conditions: An Analysis of Currently Registered Psychedelics Studies in the American Drug Trial Registry. Registered clinical trials on psychedelic drugs in clinicaltrials.gov 2022 Systematic review n = 105

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