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Reporting of side-effects in clinical trials of psilocybin-assisted psychotherapy for psychiatric conditions: systematic review

Jonathon Marinis, Sarah Clarke, Alexandre A. Guerin, Adam J. Guastella, Gillinder Bedi

BJPsych Open November 1, 2025 DOI: 10.1192/bjo.2025.10847 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Randomized Peer reviewed
Sample size 24
Population Clinical trials of psilocybin-assisted psychotherapy for psychiatric conditions
Topics Psilocybin Psychedelic-assisted therapy
Keywords Clinical trial Medline Systematic review Alternative medicine Drug trial Psychotherapist
Citations 2
Key findings Side-effects reporting in PAP trials is inconsistent, with only six of 24 trials achieving high reporting quality, and all randomized controlled trials showing high risk of bias for side-effects outcomes.

Abstract

Background: Psilocybin-assisted psychotherapy (PAP) has gained attention as a promising intervention for conditions including depression, anxiety and post-traumatic stress disorder, but understanding of its side-effects is limited. This review evaluates the quality of side-effects reporting in PAP trials, to guide treatment, policy and research.

Aims: To assess side-effects reporting quality in PAP trials for psychiatric conditions, comparing published articles and ClinicalTrials.gov records.

Method: A PROSPERO-registered review (no. CRD42023458960) included English-language PAP trials (2005–2024) identified via Embase, CENTRAL, PubMed and reference searches. Reporting quality was assessed using the CONSORT Harms extension, categorised as either high (17–21), moderate (12–16), low (7–11) or very low (0–6). Randomised controlled trials underwent risk of bias analysis, and descriptive statistics compared side-effects across sources.

Results: Twenty-four trials were included. Reporting quality was high in six studies, moderate in four, low in nine and very low in five. All randomised controlled trials ( n = 9) showed high risk of bias for side-effects outcomes. Variability in reporting hindered comparisons between articles and ClinicalTrials.gov, underscoring the need for standardisation. Overall, there was no evidence of systematic underreporting of side-effects in published articles compared with trial registers.

Conclusions: Side-effects reporting in PAP trials is inconsistent but is improving over time. Existing evidence has a high risk of bias. Future trials should align with best-practice guidelines for side-effects reporting. Discussions with patients should prioritise findings from high-quality studies and emphasise the current uncertainty regarding PAP side-effects.

Comparable studies

Other systematic reviews and meta-analyses on psilocybin and psychedelic-assisted therapy, most cited first.

Study Year Design Participants
A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy 2020 Systematic review
Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Participants in studies of psychedelic therapy for depressive symptoms (Major... 2023 Systematic review with meta-analysis n = 14
Psilocybin-assisted therapy for depression: A systematic review and meta-analysis. Patients diagnosed with life-threatening illnesses or major depressive disorder 2023 Systematic review and meta-analysis n = 686
United States National Institutes of Health grant funding for psychedelic-assisted therapy clinical trials from 2006-2020. 2022 Systematic review
Safety and risk assessment of psychedelic psychotherapy: A meta-analysis and systematic review. Human subjects in studies of psychedelic-assisted psychotherapy 2024 Systematic review and meta-analysis n = 30

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