Effects of psilocybin-assisted therapy on personality in patients with treatment resistant depression
Abstract
Psilocybin (4-phosphoryloxyl-N,N-dimethyltryptamine), a natural tryptamine occurring in psilocybe mushrooms, has shown promise in treating a range of mental health conditions, including major depressive disorder (MDD), depression and anxiety in advanced-stage cancer, and alcohol use disorder. There is preliminary evidence from both non-clinical surveys of naturalistic psychedelic use and clinical trials of psilocybin therapy showing changes in personality following psilocybin use. In particular, reduced neuroticism and increased openness, extraversion, and absorption have been reported after psilocybin in patients with MDD (Erritzoe et al., 2018; Weiss et al., 2024). Furthermore, personality may moderate response to psilocybin treatment, such that those with higher neuroticism at baseline show less improvement in depression after treatment (Erritzoe et al., 2018). The Psilocybin in Depression Resistant to standard treatments (PsiDeR) trial was a two arm, double-blind, randomised, placebo-controlled phase 2 trial evaluating feasibility and safety of 25mg psilocybin versus placebo in adults with treatment resistant depression (TRD). The aim of this secondary data analysis is to examine change in personality dimensions (including openness, conscientiousness, extraversion, agreeableness, neuroticism, and absorption) over the course of treatment with psilocybin or placebo in patients with TRD. Personality as a moderator of treatment response will also be explored.
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