Anxiety DisordersHealthy VolunteersPersonality & Trait FactorsPsilocybin

Prediction of psilocybin response in healthy volunteers

This pooled-data study (n=409) looks at the non-pharmacological influences on the psychedelic experience. This includes the current mood state, drug pre-experiences, expectancies, and social and environmental variables. The drug dosage, personality trait absorption, and being emotionally excitable were the top predictors of pleasant and peak/mystical experiences.

Authors

  • Franz Vollenweider
  • Matthias Kometer
  • Erich Studerus

Published

PLOS ONE
meta Study

Abstract

Responses to hallucinogenic drugs, such as psilocybin, are believed to be critically dependent on the user’s personality, current mood state, drug pre-experiences, expectancies, and social and environmental variables. However, little is known about the order of importance of these variables and their effect sizes in comparison to drug dose. Hence, this study investigated the effects of 24 predictor variables, including age, sex, education, personality traits, drug pre-experience, mental state before drug intake, experimental setting, and drug dose on the acute response to psilocybin. The analysis was based on the pooled data of 23 controlled experimental studies involving 409 psilocybin administrations to 261 healthy volunteers. Multiple linear mixed effects models were fitted for each of 15 response variables. Although drug dose was clearly the most important predictor for all measured response variables, several non-pharmacological variables significantly contributed to the effects of psilocybin. Specifically, having a high score in the personality trait of Absorption, being in an emotionally excitable and active state immediately before drug intake, and having experienced few psychological problems in past weeks were most strongly associated with pleasant and mystical-type experiences, whereas high Emotional Excitability, low age, and an experimental setting involving positron emission tomography most strongly predicted unpleasant and/or anxious reactions to psilocybin. The results confirm that non-pharmacological variables play an important role in the effects of psilocybin.

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Research Summary of 'Prediction of psilocybin response in healthy volunteers'

Introduction

Responses to classical hallucinogens such as psilocybin vary substantially between and within individuals even at fixed doses, a phenomenon commonly attributed to non-pharmacological factors summarised as "set" (personality, preparation, current mood) and "setting" (physical, social, cultural context). Earlier literature, much of it older and methodologically limited, has implicated personality, pre-session mood, social support, expectations, age, body morphology, group size, and prior drug experience as potential determinants of hallucinogen responses, but most studies examined few predictors at a time and relied on simple correlations rather than multivariable approaches that could adjust for confounding and compare effect sizes across predictors. This paper pools raw data from 23 controlled experimental studies to investigate the relative importance of 24 predictor variables (demographic, personality, recent psychological state, prior drug use, session environment, and drug dose) for acute subjective responses to psilocybin in healthy volunteers. The primary goal was to identify which non-pharmacological factors meaningfully predict different dimensions of altered states of consciousness, and to compare their effect sizes with that of drug dose, using modern statistical methods (multiple imputation, linear mixed models, bootstrap variable selection). This work is intended to inform safety screening, standardisation of experimental designs, covariate adjustment in trials, and mechanistic hypotheses linking individual differences to neurobiology.

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Study Details

References (11)

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50 cited
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