Review of trials finds psychedelics generally well-tolerated

The fast-expanding use of psychedelic drugs for medical purposes necessitates a greater understanding of the drugs' potential adverse effects. Investigators conducted a systematic review of studies of psychedelic administration in clinical and research settings and a meta-analysis of data on adverse events. They conducted a comprehensive database search for studies published through Feb. 8, 2024. Major outcomes included adverse events serious enough to require medical intervention. Adverse events of special interest included psychotic disorder, manic symptoms, suicidality, cardiovascular events, and hallucinogen persisting perception disorder. Adverse events were stratified by the population categories of healthy individuals with no medical or neuropsychiatric disorder, outpatients with a neuropsychiatric disorder, and inpatients requiring continuous facility-based care for a neuropsychiatric disorder. A total of 114 studies comprising 3,504 participants reported on adverse events. Approximately 16.5% of the inpatients had a psychotic disorder diagnosis. No early serious adverse events were reported among healthy individuals receiving psilocybin, lysergic acid diethylamide (LSD), or dimethyltryptamine (DMT). None of 618 outpatients receiving psilocybin experienced an early serious adverse event. A total of 2.1% of psychiatric inpatients receiving LSD (11 of 517) had an early serious adverse event, including four psychotic episodes. Follow-up analyses found no delayed serious adverse events in healthy individuals and small percentages of delayed serious adverse events in outpatients and inpatients. Suicidal ideation and behavior were also rare. “Our results broadly indicate that while medically or psychiatrically significant [adverse events] (e.g., psychosis, suicidality) are relatively rare, these events are often serious when they occur,” the review's authors wrote. [Hinkle, J., et al. (2024). JAMA Psychiatry. https://doi.org/10.1001/jamapsychiatry.2024.2546]