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Can psilocybin be safely administered under medical supervision? A systematic review of adverse event reporting in clinical trials

Someone using tweezers to pick up mushrooms


Jeremy Roscoe, Olivia Lozy


March 16, 2022

Psilocybin is a naturally occurring psychoactive chemical produced by various species of mushroom, mainly in the psilocybe genus. Human consumption of psilocybin, primarily for its psychoactive properties, dates back thousands of years (Tylš et al., 2013). It was first isolated in 1958 by Albert Hoffmann, who was later the first to synthesize it (Hofmann et al., 1958). Soon thereafter, the United States passed the Controlled Substance Act of 1971. This legislation classified psilocybin as a schedule I drug, a category for substances which meet the following three criteria (21 U.S.C. § 812, 2021):

  1. The drug or other substance has a high potential for abuse.

  2. The drug or other substance has no currently accepted medical use in treatment in the United States.

  3. There is a lack of accepted safety for use of the drug or other substance under medical supervision.

In the time between the isolation of psilocybin and its Schedule I designation, a myriad of studies were published investigating the efficacy of psilocybin for the treatment of various psychiatric disorders (Grinspoon and Bakalar, 1981). As the United States faces a growing behavioral health crisis (Belouin and Henningfield, 2018), it is becoming paramount that all applicable, scientifically supported treatment options are considered. Numerous clinical trials have investigated psilocybin in the decades since its legal designation. This paper seeks to systematically review these trials for reports of adverse events, drug tolerability, and drug safety, in order to evaluate the scientific support for psilocybin’s classification under criterion number three of the schedule I designation: There is a lack of accepted safety for use of the drug or other substance under medical supervision.

Data were collected by using the PubMed database and conducting a search on November 24, 2021, with the search term psilocybin and applying the clinical trial filter. Only primary reports on the sole administration of psilocybin by a medical professional were included for analysis, excluding trials wherein psilocybin was not administered, trials wherein psilocybin was exclusively co-administered with other drugs, articles that were not clinical trials, and articles that were repeat analyses of already included trials. 52 included publications were closely examined for reports of adverse events, drug tolerability, and drug safety. Zero of these articles reported psilocybin to be unsafe, while 27 of the included trials suggested that psilocybin is safe to administer under proper medical supervision.

The results of this analysis strongly attest to psilocybin’s safety and point towards a need for the revision of psilocybin’s drug scheduling. In this analysis, out of 550 individuals, no one suffered from a serious adverse event; however, sparse reports from studies not included in this analysis point to the potential of psychiatric side effects arising after administration, which warrants further research into the safety profile and abuse potential of psilocybin to extend the findings of this systematic analysis.

This research was published in the Drug Science, Policy and Law Journal the definitive source of evidence-based information and comment for academics, scientists, policymakers, frontline workers and the general public on drugs and related issues.

For open-access to the full report of this research, see below:

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