Design This study represents secondary data analysis of a phase I, double-blind, randomised, placebo-controlled trial investigating the safety of a single dose of 10 or 25 mg psilocybin compared to placebo in 89 healthy participants, conducted at King’s College London (EudraCT number: 2018-000978-30). Participants were followed up over 12 weeks. The trial was funded and sponsored by COMPASS Pathways. Further details of the trial and the primary analyses are presented in Rucker et al. (2022).

Abstract 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.

COMP360 - Effects of psilocybin on personality, psychiatric symptoms, and values: Exploring mediating effects of the acute psychedelic experience