The Tolerability and Safety of Psilocybin in Psychiatric and Substance-Dependence Conditions: A Systematic Review

A systematic review of 16 clinical trials found that psilocybin is generally well tolerated in patients with psychiatric or substance-dependence conditions. The most common side effects were temporary nausea and headache. Some participants experienced transient anxiety, and three received a benzodiazepine for severe anxiety during the session. Psilocybin caused modest increases in blood pressure and heart rate, with one participant requiring an antihypertensive for sustained high blood pressure. No cases of psilocybin-induced psychosis or Hallucinogen Persisting Perception Disorder were reported. The evidence suggests psilocybin has a favorable safety profile and may offer an alternative treatment for patients who do not respond to standard therapies.

Study at a glance

Abstract

Objective: The objective of this systematic review is to determine the tolerability and safety of psilocybin in a variety of psychiatric and substance-dependence conditions. Data sources: A systematic review was conducted using Embase, PubMed, Cochrane Central, and Web of Science through September 2023 using the following terminology: “psilocybin” AND “mental-disease” OR “substance-dependence” AND “disease-therapy,” in addition to other synonymous key words. Study selection and data extraction: Literature reporting acute effects and safety data following the use of psilocybin as the pharmacologic intervention in a clinical trial in adult patients with a psychiatric or substance-dependence condition were included. Following the application of inclusion and exclusion criteria, 16 studies were ultimately included in this review. Data synthesis: The most common treatment-emergent adverse effects reported were transient nausea and headache. Transient anxiety was reported as a frequent psychiatric effect, and 3 participants received a benzodiazepine for refractory anxiety during the psilocybin session. Psilocybin demonstrated modest increases in blood pressure and heart rate, and 1 participant received an antihypertensive for sustained hypertension during the psilocybin session. No cases of psilocybin-induced psychosis or Hallucinogen Persisting Perception Disorder were reported. Relevance to patient care and clinical practice: Treatment resistance remains a concern for psychiatric patients and novel therapies are needed to help alleviate the burden of morbidity and mortality. Psilocybin demonstrates promising acute and long-term safety that may allow for its use in psychiatric or substance-dependence conditions as an alternative to standards of care or in treatment-resistant patients. Conclusions: Psilocybin has demonstrated tolerability and safety in recent literature that has investigated its therapeutic potential in a variety of psychiatric or substance-dependence conditions.