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

Psilocybin, a hallucinogenic compound, dose-dependently induced profound changes in mood, perception, thought, and self-experience, but most subjects described the experience as pleasurable, enriching, and non-threatening. Acute adverse drug reactions—strong dysphoria or anxiety—occurred only at the two highest doses in a small proportion of subjects, and were managed with interpersonal support without medication. Follow-up showed no subsequent drug abuse, persisting perception disorders, prolonged psychosis, or long-term impairment. The findings suggest that moderate doses given to healthy, high-functioning, well-prepared subjects in a carefully monitored research setting carry an acceptable level of risk.

Study at a glance

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.