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.
Highlights
Responses to classical hallucinogens, such as psilocybin, strongly vary between and within subjects, even when the drug dose is kept constant [1,2]
To further elucidate the dependency of psilocybin response on set and setting, the present study investigates the relative importance of 24 predictor variables, including age, sex, years of education, body mass index, personality traits, drug preexperience, mental state before drug intake, psychological distress, experimental setting, and drug dose
The selection frequencies of the predictor variables and models as a result of the bootstrap selection procedures are provided in Supplementary Table S3
Summary
Responses to classical hallucinogens, such as psilocybin, strongly vary between and within subjects, even when the drug dose is kept constant [1,2]. Since human hallucinogen research has been dormant for almost three decades and has only come to a revival recently [8], most of what we know today about non-pharmacological predictors of hallucinogen response is based on a small number of older studies, many of which do not conform to modern methodological standards. Most of these studies suggest that responses to classical hallucinogens are dependent at least to some degree on the personality structure (e.g., [9,10,11,12,13,14,15,16]). Further influencing factors include the mood state immediately before drug intake (e.g., [14,17]), peer-support [18], estimated emotional support [3], expectations of the subjects (e.g., [3,14,17]), age [17,19], body morphology [17], size of the group in which the drug is taken [3], and drug pre-experiences [3,17]
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