Predicting the Intensity of Psychedelic-Induced Mystical and Challenging Experience in a Healthy Population: An Exploratory Post-Hoc Analysis

Introduction

Psychedelics are being actively investigated in clinical research, and during acute administration users commonly report profound subjective effects that investigators label as mystical and/or challenging experiences. Mystical experience (ME) is characterised by features such as ineffability, deeply felt positive mood, sacredness and a sense of unity; oceanic boundlessness (OBN) on the 5D-ASC is a quantitative measure closely related to ME. Challenging experiences include physiological arousal and psychological distress, and the dread of ego dissolution (DED) subscale of the 5D-ASC captures aspects of this domain. Previous studies and systematic reviews have linked ME to therapeutic benefit in multiple psychiatric contexts, but evidence around how ME and challenging experience predict clinical outcomes is mixed and the predictors of the intensity of these acute states remain incompletely established. Ko and colleagues set out to explore clinical predictors of the intensity of psilocybin-induced mystical and challenging experiences by analysing data from an existing Phase I randomised, double-blind, placebo-controlled trial. The investigators examined dosage, five-factor personality traits, baseline affect, and individual variables (age, biological sex, prior psilocybin exposure) as potential predictors of OBN (mystical-like experience) and DED (challenging experience). A set of directional hypotheses was specified for dose, age, prior experience, sex, personality dimensions (notably openness and neuroticism), and positive/negative affect.