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

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.

KEYWORDS:

• Psychedelics
• meta-analysis
• review
• placebo-controlled
• randomized clinical trials

Acknowledgments

We thank Brandon Strickland for his help during the literature search. During his work on this study, Dr. Davis was supported by a NIDA T32 under grant #DA07209. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. J.B.L., G.B., and A.K.D. conceived the meta-analysis and facilitated data extraction. J.B.L. and C.C. conducted risk of bias assessment and assisted in data analysis. C.C. and R.L. conducted literature review and extracted data. All authors assisted in drafting and editing the manuscript.

Disclosure 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.

Supplementary material

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Additional information

Funding

This work was supported by the National Institute on Drug Abuse [DA07209].