Effects of psilocybin on personality, psychiatric symptoms, and values: Exploring mediating effects of the acute psychedelic experience

Background: Changes in well-being, personality, and personal values have been documented post-psilocybin; however, evidence from placebo-controlled trials is limited.

Aims: To examine the effects of psilocybin versus placebo on psychiatric symptoms, personality, and personal values in healthy participants. Potential mediators were also explored.

Methods: This secondary analysis used data from a phase I, double-blind, randomised, placebo-controlled trial testing a single dose of 10 mg ( n = 30) or 25 mg psilocybin ( n = 30) versus an inert placebo ( n = 29) in 89 healthy participants. Effects of psilocybin on personality (Neo Five-Factor Inventory; NEO-FFI), psychiatric symptoms (Symptom Checklist-90; SCL-90), and values (Life Changes Inventory; LCI) at short- (day 8) and long-term follow-up (day 85) were analysed using mixed-effects models. Group differences in cognitive flexibility (Intra-Extra Dimensional Set Shift task; IED) at day 8 were analysed using a Kruskal–Wallis test. Potential mediating effects of the acute psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire; 5D-ASC) were explored.

Results: No between-group differences were found on the NEO-FFI, SCL-90, or IED. Both psilocybin groups showed greater LCI absolute change scores at both follow-up points compared to placebo. The 5D-ASC oceanic boundlessness subscale partially mediated these changes. Oceanic boundlessness also fully or partially mediated differences across several LCI subscales, and auditory alterations mediated differences on one subscale.

Conclusions: The acute psychedelic experience, namely oceanic boundlessness and, to a lesser extent, auditory alterations, mediates self-reported changes in values in healthy volunteers. Findings from this exploratory study are tentative and should be replicated in larger samples.