A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy
This meta-analysis of nine placebo-controlled trials (n=211) showed a very large effect size (g=1.21) of treatment on four mental health conditions (PTSD, end-of-life anxiety, depression, social anxiety among autistic adults).
Authors
- Alan Davis
- Rafaelle Lancelotta
- Jason Luoma
Published
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.
Research Summary of 'A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy'
Introduction
Clinical research on classical psychedelics such as LSD and psilocybin was widespread in the 1950s–1960s but largely ceased after reclassification and bans in the 1970s. Earlier studies suggested therapeutic potential for non-psychotic mental health difficulties but generally lacked modern trial features such as placebo controls, validated outcome measures, blinding, and randomization. Interest has resurged in recent decades and newer randomized, placebo-controlled trials have been published for a range of compounds, including psilocybin, LSD, ayahuasca (containing DMT plus MAOI alkaloids), and MDMA. Luoma and colleagues set out to synthesise the modern randomized, placebo-controlled evidence base for psychedelic-assisted therapy. The primary aim was to pool between-group effect sizes at each study's primary endpoint; secondary aims included comparing classical psychedelics versus MDMA, assessing durability of effects where placebo control was maintained at follow-up, characterising between-study variability and risk of bias, and exploring potential moderators of effect size. The investigators framed these interventions collectively as psychedelic-assisted therapies because trials typically combine 1–3 dosing sessions with structured psychotherapeutic support (the ‘‘set and setting’’ model).
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Study Details
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- APA Citation
Luoma, J. B., Chwyl, C., Bathje, G. J., Davis, A. K., & Lancelotta, R. (2020). A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy. Journal of Psychoactive Drugs, 52(4), 289-299. https://doi.org/10.1080/02791072.2020.1769878
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