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

Abstract

This systematic review investigates whether clinical trials of psilocybin support criterion number three of the drug's 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.

Experiences of psilocybin treatment for clinical conditions: A qualitative meta‐synthesis

“…There is no evidence available on whether further maintenance doses are needed to maintain the antidepressant effect or whether its integration into a course of psychotherapy would fix its effects. None of the studies to date has identified adverse events (Roscoe & Lozy, 2022). Two studies surveyed people who had had challenging experiences with psilocybin in non-clinical settings (Bienemann et al, 2020;Carbonaro et al, 2016).…”

The changing outlook of psychedelic drugs: The importance of risk assessment and occupational exposure limits

“…Even though these molecules had restricted use for decades, reports of human recreational use and nonclinical studies have shown that these classical psychedelics are generally safe and well tolerated and have minimal potential for abuse, physical dependence, and drug‐seeking behavior (Ermakova et al, 2022; Nichols, 2016; Roscoe & Lozy, 2022; Sarris et al, 2022). The low potential for dependence has been suggested to be due to the lack of direct effects of psychedelics on brain dopaminergic systems (Nichols, 2016; Schlag et al, 2022).…”

“…Other neurologic and neuropsychiatric effects can include ataxia, hyperreflexia, clonus, severe agitation, psychosis, paranoia, delusions, confusion, excited delirium, echolalia, anterograde amnesia, and catalepsy. The psychedelic experience with these drugs has been referred to as a mystical and/or spiritual experience, being one of the most meaningful experiences of the user (Brito‐da‐Costa et al, 2020; Fuentes et al, 2019; Reckweg et al, 2021; Roscoe & Lozy, 2022; Schlag et al, 2022).…”

“…Common physiological adverse effects of these serotonergic psychedelics include increase in BP (hypertension) and heart rate, tachypnea, hyperthermia, abdominal pain, trismus, sweating, sialorrhea, diaphoresis, palpitations, drowsiness, dysphoria, mydriasis, nausea, diarrhea and vomiting. In general, in clinical trials, these adverse effects were mild and transient and resolved without medical intervention (Brito‐da‐Costa et al, 2020; Fuentes et al, 2019; Reckweg et al, 2021; Roscoe & Lozy, 2022; Schlag et al, 2022).…”

“…Another possible risk of psychedelic drug administration is the exacerbation of psychotic disorders or the generation of prolonged psychotic reactions, which could be related to the predisposition of the subjects (Fuentes et al, 2019; Johnson et al, 2008). It is very common as an exclusion criterion for psychedelic clinical trials not to include persons with a history of psychiatric disorders or who are related to people with psychotic disorders, epilepsy, or paranoid traits (Fuentes et al, 2019; Johnson et al, 2008; Roscoe & Lozy, 2022; Sarris et al, 2022).…”