Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies

TLDR

Psilocybin is increasingly studied, but limited data on subjective side effects has made its controlled medical use controversial. The study pooled data from eight double‑blind placebo‑controlled trials to analyze acute, short‑ and long‑term subjective effects of psilocybin in healthy adults. 110 healthy participants received 1–4 oral doses of psilocybin ranging from 45 to 315 µg/kg. Psilocybin produced dose‑dependent profound mood and perceptual changes that were generally pleasurable and non‑threatening, with acute dysphoria or anxiety occurring only at the highest doses in a minority of subjects and managed with support, and no long‑term adverse effects or substance misuse were observed, indicating an acceptable risk profile for moderate doses in a controlled setting.

Abstract

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1–4 oral doses of psilocybin (45–315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.