Anxiety DisordersHealthy VolunteersSubstance Use Disorders (SUD)SchizophreniaPsilocybin

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

Pooled analysis of eight double‑blind, placebo‑controlled studies in 110 healthy volunteers found that psilocybin produced dose‑dependent profound changes in mood, perception, thought and self‑experience that most participants described as pleasurable and enriching, while acute dysphoric or panic reactions occurred only at the highest doses and were resolved with interpersonal support without pharmacological intervention. Follow‑up found no evidence of subsequent drug abuse, persistent perceptual disorders, prolonged psychosis or long‑term functional impairment, suggesting moderate doses in well‑prepared, closely monitored research settings carry an acceptable level of risk.

Authors

  • Franz Vollenweider
  • Matthias Kometer
  • Erich Studerus

Published

Journal of Psychopharmacology
meta Study

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.

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

Introduction

Psilocybin is a classical serotonergic hallucinogen found in Psilocybe mushrooms and has been used historically in ritual contexts and, more recently, in psychopharmacological research. Earlier clinical and experimental work showed that psilocybin produces an altered state of consciousness (ASC) characterised by marked changes in perception, mood, thought, and self-experience, and that its acute effects are generally shorter in duration than those of LSD. However, many early human studies lacked standardisation, adequate controls, follow-up, or sufficiently large and representative samples, leaving uncertainties about dose–response relations, the incidence of acute and subacute adverse reactions, and possible long-term psychological sequelae such as persisting perceptual disturbances or increased drug use. Studerus and colleagues set out to address these gaps by pooling raw data from eight double-blind, placebo-controlled experimental studies conducted in their laboratory between 1999 and 2008. Their aim was to describe acute, subacute (24 h), and long-term (8–16 months) subjective effects and side effects of psilocybin in healthy volunteers using validated psychometric instruments, and to evaluate dose–response relationships and the tolerability of the drug when administered in a controlled research setting.

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Study Details

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