INTRODUCTION: Psilocybin, a classical psychedelic, has been rescheduled for use in psilocybin-assisted psychotherapy for treatment-resistant depression in Australia. While evidence for its use is promising, understanding the associated risks is crucial. Accordingly, this review aims to collate adverse event data from psilocybin-assisted psychotherapy clinical trials and evaluate its definition, way of measurement and reporting.
METHODS: A systematic method was employed to identify clinical trials related to the use of psilocybin-assisted psychotherapy in clinical populations that reported on adverse events. The quality assessment focused on relevant criteria related to adverse event definition, monitoring and reporting methods.
RESULTS: A total of 24 articles were included. The studies reported heterogeneous psilocybin doses, study designs and indications. Physical and psychological adverse events during and after psilocybin sessions were examined, revealing variations in measuring, reporting methods and occurrences. The most common adverse events during and after sessions included elevated blood pressure, headaches, nausea, vomiting, fatigue and anxiety. In addition, both suicidal ideation and behaviour were observed infrequently and mainly in participants with a history of suicidal ideation or suicide attempt(s).
CONCLUSION: The review highlights the need to standardise the defintion of an adverse event, including how they are measured and reported, in psychedelic clinical trials to ensure consistent reporting across studies. In addition, screening participants for suicidality history and ongoing monitoring remains important, given the potential risk identified in the literature. However, based on the available data, the safety of psilocybin-assisted psychotherapy is generally supported, and no deaths were attributed to psilocybin. Nevertheless, cautious optimism is needed due to the preliminary nature and heterogeneity of the safety data.
