Efficacy and Safety of Four Psychedelic-Assisted Therapies for Adults with Symptoms of Depression, Anxiety, and Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis

A systematic review and meta-analysis of 18 studies found that psychedelic-assisted therapies—psilocybin, LSD, MDMA, and ayahuasca—were well tolerated and produced large reductions in depression symptoms across various diagnoses. Psilocybin showed a large effect (standardized mean difference -1.92) and MDMA a moderate-to-large effect (standardized mean difference -0.71). However, the certainty of the evidence was low to very low due to small sample sizes, blinding issues, study heterogeneity, and publication bias. The results are promising but highlight the need for larger, more rigorous studies.

Study at a glance

Abstract

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.