Journal of psychoactive drugsNov 16, 2023

Effectiveness and Safety of Four Psychedelic Therapies for Adults with Depression, Anxiety, and PTSD

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 25, 2026

Abstract

Eighteen studies indicated that psilocybin and MDMA may significantly reduce depression symptoms, with effect sizes of -1.92 and -0.71, respectively.

Psychedelic therapies were generally well tolerated among participants.
Psilocybin and MDMA demonstrated large effect sizes for alleviating depression symptoms in a diverse group of individuals.
The evidence supporting these findings is associated with low to very low certainty due to various methodological issues.
Limitations included small sample sizes, lack of blinding, and potential publication bias.
There is a need for more robust studies to further investigate the effectiveness and safety of these therapies.

Simplified

There has been a resurgence in psychedelic research for managing psychiatric conditions in recent years. This study aimed to present a comprehensive review of the current state of the field by applying a systematic search strategy for articles on the effectiveness and tolerability of four psychedelic-assisted therapies (psilocybin, lysergic acid diethylamide [LSD], 3,4-Methylenedioxymethamphetamine [MDMA], and ayahuasca) for adults with symptoms of depression, anxiety, and posttraumatic stress disorder (PTSD). Psychometric scores and adverse events were pooled using random-effects meta-analysis models with Hedges' g bias-corrected standardized mean differences (g) and rate ratios (RR) with 95% confidence intervals (CI). Bias evaluation followed PRISMA and Cochrane guidelines. Eighteen studies were identified, which suggested that psychedelic therapies were well tolerated and presented a large effect size for the management of depression symptoms in a transdiagnostic population with psilocybin (g = -1.92, 95% CI, -2.73 to -1.11) and MDMA (g = -0.71; 95% CI, -1.39 to -0.03). These are promising results that complement the current literature. However, evidence certainty was low to very low due to methodological limitations, small sample size, blinding, study heterogeneity, and publication bias. These results also highlight the need for more adequately powered studies exploring these novel therapies.

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Effectiveness and Safety of Four Psychedelic Therapies for Adults with Depression, Anxiety, and PTSD

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