Efficacy and Safety of Psychedelics in Mental Disorder Cases - An Umbrella Review of Meta-Analyses of Randomized Controlled Trials

Sep 30, 2026

Uploaded by Adam

Psychedelic-assisted therapy is increasingly studied as a potential treatment for mental disorders, yet a unified synthesis across substances and indications remains limited. This umbrella review evaluates effectiveness and safety of psychedelic-assisted therapy, focusing on psilocybin, MDMA, and LSD, across major psychiatric conditions including depression, PTSD, and substance use disorders. Data from 23 meta-analyses covering over 100 randomized controlled studies were standardized using Hedges’ g, assessed by AMSTAR2, and appraised with GRADE.

LanguageEnglish

CategoryHealthcare

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Pages17

Reading Time43 min

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Abstract

1. Introduction

Systematic Review Efficacy and Safety of Psychedelics in Mental Disorder Cases: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials Monika Dominiak 1, Adam G˛edek 2, *, Szymon Modrzejewski 3, Agnieszka Permoda-Pachuta 4 and Anna Zofia Antosik 5 Academic Editor: Napoleon Waszkiewicz Received: 13 November 2025 Revised: 12 December 2025 Accepted: 23 December 2025 Published: 29 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland 2 Third Department of Psychiatry, Institute of Psychiatry and Neurology, 02-957 Warsaw, Poland 3 Faculty of Medicine, Medical University of Lublin, 20-059 Lublin, Poland 4 Department of Neuroses, Personality Disorders and Eating Disorders, Institute of Psychiatry and Neurology, 02-957 Warszawa, Poland 5 Department of Psychiatry, Faculty of Medicine, Collegium Medicum, Cardinal Wyszynski University in Warsaw, 01-938 Warszawa, Poland * Correspondence: [agedek@ipin.edu.pl](agedek@ipin.edu.pl) Abstract Background: Psychedelic-assisted therapy is gaining renewed attention as a potential treatment for various mental disorders. Despite increasing numbers of randomized controlled trials (RCTs) and meta-analyses, a comprehensive synthesis of the evidence across different substances and indications is lacking. This umbrella review aims to evaluate the effectiveness and safety of psychedelic-assisted therapy—primarily psilocybin, MDMA, and LSD—across major psychiatric disorders, including depression, post-traumatic stress disorder (PTSD), and substance use disorders. Methods: We systematically identified and synthesized data from 23 meta-analyses encompassing over 100 primary studies. Outcomes were standardized and re-expressed as Hedges’ g to enable cross-study comparisons. Study quality was assessed using AMSTAR2, and certainty of evidence was evaluated via the GRADE framework. Results: The number of identified meta-analyses differed markedly depending on the substance and clinical indication: psilocybin for depression (n = 9) and MDMA for PTSD (n = 10) had the strongest evidence base, while fewer meta-analyses were available for LSD in alcohol use disorder (n = 2) and depression (n = 2), ayahuasca in depression (n = 2), and MDMA in autism spectrum disorder (n = 2) . Psilocybin demonstrated large effect sizes in major depression (Hedges’ g ≈ 1.05), with some evidence of sustained benefits up to six months. MDMA showed very large effects in reducing PTSD symptoms (Hedges’ g ≈ 1.24), often after 2–3 sessions. LSD yielded short-term benefits for alcohol use disorder (OR ≈ 2.0), though effects declined over time. Across studies, adverse events were generally mild and transient, with no consistent signal for serious harm. Considerable methodological variability was observed, including small and sometimes overlapping samples, heterogeneity, risk of bias, and limited long-term data. These constraints should betaken into account when interpreting the overall findings. Conclusions: Current evidence supports the short-term efficacy and safety of psychedelic-assisted therapy for selected psychiatric disorders, particularly depression and PTSD. However, the low methodological quality of studies and most meta-analyses, as well gaps in long-term safety data highlight the need for high-quality studies. Keywords: psychedelics; psilocybin; depression; MDMA; PTSD; post-traumatic stress disorder; alcohol use disorder 1. Introduction Psychedelics are a group of psychoactive substances that are gaining renewed interest in medicine, especially in psychiatry. Their common feature is the psychedelic effect consisting in changing the sense of time and space, experiencing transcendental, mystical experiences so-called “ego dissolution” or a sense of unity with th

FAQs

What is the purpose of this umbrella review?

To evaluate the effectiveness and safety of psychedelic-assisted therapy across major psychiatric disorders, synthesizing evidence from multiple meta-analyses of randomized controlled trials.

Which psychedelic-substance and disorder pairs showed the strongest evidence base?

Psilocybin for depression (n = 9) and MDMA for PTSD (n = 10) had the most robust evidence among the examined indications.

How are outcomes and study quality assessed in this review?

Outcomes are standardized and re-expressed as Hedges’ g for cross-study comparisons, study quality is assessed with AMSTAR2, and certainty of evidence is evaluated using the GRADE framework.

Sep 30, 2026

Uploaded by Adam