Psilocybin treatment for symptoms of depression: a living systematic review, meta-analysis, and data resource
Abstract
<h4>Importance</h4> Depression is a major cause of disability worldwide, motivating substantial interest in psilocybin as a potential treatment. <h4>Objective</h4> To conduct a systematic review and meta-analysis of psilocybin’s impact on depressive symptoms and provide a living open data resource. <h4>Data Sources</h4> PubMed, Embase, Scopus, Web of Science, and PsycINFO retrieved by a systematic search up to July 1, 2025. <h4>Study Selection</h4> We included randomized controlled trials of psilocybin or psilocybin-assisted therapy compared against a placebo or waitlist condition. <h4>Data Extraction and Synthesis</h4> Data extraction was completed independently by two extractors. A random-effects meta-analysis was used to synthesize data. Risk of bias was assessed with Cochrane’s RoB 2.0 tool. <h4>Main Outcomes and Measures</h4> The main outcome was the standardized mean difference (Hedges’ g ) in depression scores at the primary study endpoint. <h4>Results</h4> Twelve studies comprising 711 participants were included in the database, with nine of those studies (n = 529) included in our primary model. Of the nine studies included in the primary model, two had a high risk of bias, four had some concerns, while three had a low risk of bias. Compared to control conditions, psilocybin showed a greater reduction in depression scores, with a pooled Hedges’ g = –0.91 (95% CI, [-1.35; –0.48]; k = 9; p = 0.0013, I 2 = 58.1%, tau 2 = 0.13, n = 501). Sensitivity analyses revealed robust effects consistent with the primary model across a variety of design parameters and analysis choices, while also suggesting that waitlist control and crossover design studies contribute a large amount of heterogeneity to the primary model. Meta-regression revealed that psilocybin’s effects were rapid and consistent over several weeks (intercept = –0.92 [-1.26; –0.58], p < 0.0001; slope = 0.0009 [-0.0023; 0.0041], p = 0.57). <h4>Conclusions and Relevance</h4> This systematic review and meta-analysis suggests that psilocybin-assisted therapy results in substantial decreases in depressive symptoms across studies to date. However, many studies have small sample sizes or risk of bias. This living systematic review, meta-analysis, database, and online dashboard will continue to be updated as evidence emerges, providing a valuable resource for researchers in a rapidly evolving field. <h4>Key Points</h4> <h4>Question</h4> What is the efficacy of psilocybin or psilocybin-assisted therapy for depressive symptoms? <h4>Findings</h4> In this living systematic review and meta-analysis, the initial evidence suggests that psilocybin is more effective in reducing depression symptoms compared to control conditions. Our publicly released database and interactive dashboard contains over 200 effect sizes from 12 randomized clinical trials testing psilocybin’s impacts on depression and will be updated regularly to keep pace with this rapidly moving field. <h4>Meaning</h4> The current evidence suggests promise for psilocybin therapy for depression, though more studies are needed.
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