Adverse event reporting and management in psilocybin therapy clinical trials: A systematic review to guide clinical and research protocol development

A systematic review of 42 clinical studies involving 1,068 participants found that psilocybin, when administered in controlled settings, has a favorable safety profile. Common adverse events included headache, transient increases in blood pressure, and nausea, which typically resolved on their own. Serious adverse events were reported infrequently, in only 2 of the 42 studies, and were limited to participants with underlying depressive disorders, such as suicidal behavior or hospitalization. All studies had a high risk of bias due to concerns regarding blinding. The review provides an outline of common and uncommon adverse events, serious adverse events, and considerations for future protocols.

Study at a glance

Abstract

Psilocybin, a psychedelic prodrug, has gained renewed interest for its potential to treat various psychiatric disorders, including depression, anxiety, and substance use disorders. While promising, concerns remain regarding its safety profile and the management of potential adverse events (AEs). This systematic review aimed to evaluate the incidence, nature, and severity of adverse events and serious adverse events (SAEs) associated with psilocybin use across diverse clinical populations. A comprehensive search was conducted across MEDLINE, Embase, and APA PsycInfo via the OVID platform, from database inception to June 5, 2024. A total of 42 clinical studies (N = 1068 participants) met inclusion criteria, all of which reported on AEs and/or SAEs following psilocybin administration. All studies were deemed to have a high risk of bias due to concerns regarding blinding. We synthesized information on common, uncommon, and SAEs, instances of suicidal ideation, methods of measuring AEs, and AEs requiring medical intervention. Reported AEs included headache, transient increases in blood pressure, and nausea, which typically resolved on their own. In rare instances, medical intervention was required. SAEs were reported infrequently in 2 of 42 studies and were limited to participants with underlying depressive disorders (e.g., suicidal behaviour, hospitalization). Overall, psilocybin appears to have a favourable safety profile when administered in controlled settings. Based on our findings, we provide an outline of commonly reported AEs, uncommon AEs, SAEs, and considerations for future clinical and research protocols.