Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial
This secondary of a Phase II study (n=84) investigates the effects of psilocybin-assisted therapy (PAT) on personality traits in alcohol use disorder (AUD). Psilocybin (2x, 25-40mg/70kg; n=44) significantly reduced neuroticism and increased extraversion and openness compared to placebo (diphenhydramine, n=40). Decreased impulsiveness correlated with lower alcohol consumption post-treatment, suggesting PAT may normalize abnormal personality traits in AUD.
Authors
- Richard Zeifman
- Michael Bogenschutz
- Stephen Ross
Published
Abstract
Objective
Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking.
Methods
Eighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psychotherapy sessions, and completed follow-up for an additional 24 weeks. Changes in personality traits (week 36 vs. baseline) were assessed with the revised NEO Personality Inventory; daily alcohol consumption was quantified using the timeline followback.
Results
Relative to the placebo group, the psilocybin group showed significant reductions in neuroticism and increases in extraversion and openness. Secondary analyses showed that reductions in neuroticism were driven by decreases in the facets depression, impulsiveness, and vulnerability; increases in openness were driven by increases in the facets openness toward feelings and fantasy. Across all participants, decreases in impulsiveness were associated with lower posttreatment alcohol consumption, and an exploratory analysis revealed that these associations were strongest among psilocybin-treated participants who continued moderate- or high-risk drinking prior to the first medication session.
Conclusions
PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.
Research Summary of 'Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial'
Introduction
Patients with alcohol use disorder (AUD) characteristically show pathological personality traits, including elevated neuroticism and reduced conscientiousness, openness, extraversion, and agreeableness, and these trait abnormalities are theorised to contribute to the persistence and treatment resistance of AUD. Prior work links personality change to substance-use outcomes and identifies impulsiveness (a facet of neuroticism) as a particularly strong predictor of alcohol consumption and related harms. Concurrently, clinical research with serotonergic psychedelics (notably psilocybin) has reported durable shifts in core personality dimensions in healthy and clinical samples, but the downstream psychological mechanisms that connect receptor-level effects to clinical benefit remain incompletely characterised, and no randomised controlled trials had examined personality change following psychedelic-assisted therapy in a substance use disorder population prior to this study. Pagni and colleagues used data from a double-blind, placebo-controlled randomised trial of psilocybin-assisted therapy (PAT) in adults with AUD to test whether PAT normalises atypical personality trait expression. They hypothesised that, relative to an active placebo plus psychotherapy, PAT would decrease neuroticism and increase extraversion, openness, and conscientiousness; that baseline personality would predict PAT-induced trait change; and that reductions in impulsiveness would be associated with reduced alcohol consumption.
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Study Details
- Study Typeindividual
- Journal
- Compound
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- APA Citation
Pagni, B. A., Zeifman, R. J., Mennenga, S. E., Carrithers, B. M., Goldway, N., Bhatt, S., O’Donnell, K. C., Ross, S., & Bogenschutz, M. P. (2025). Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial. American Journal of Psychiatry, 182(1), 114-125. https://doi.org/10.1176/appi.ajp.20230887
References (18)
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Kwan, A. C., Olson, D. E., Preller, K. H. et al. · Nature Medicine (2022)
Andersen, K. A. A., Carhart-Harris, R. L., Nutt, D. J. et al. · Acta Psychiatrica Scandinavica (2020)
Bouso, J. C., Dos Santos, R. G., Hallak, J. E. · Neuroscience and Biobehavioral Reviews (2018)
Madsen, M. K., Fisher, P. M., Stenbæk, D. S. et al. · European Neuropsychopharmacology (2020)
Carhart-Harris, R. L., Kaelen, M., Bolstridge, M. et al. · Psychological Medicine (2016)
Maclean, K. A., Johnson, M. W., Griffiths, R. R. · Journal of Psychopharmacology (2011)
Erritzoe, D., Roseman, L., Nour, M. R. et al. · Acta Psychiatrica Scandinavica (2018)
Weiss, B., Ginige, I., Shannon, L. et al. · Psychological Medicine (2023)
Perkins, D., Pagni, B. A., Sarris, J. et al. · Frontiers in Pharmacology (2022)
Bogenschutz, M. P., Forcehimes, A. A. · Journal of Humanistic Psychology (2016)
Show all 18 referencesShow fewer
Johnstad, P. G. · Journal of Psychoactive Drugs (2020)
Garcia-Romeu, A., Griffiths, R. R., Johnson, M. W. · Current Drug Abuse Reviews (2015)
Weiss, B., Miller, J. D., Carter, N. T. et al. · Scientific Reports (2021)
Netzband, N., Ruffell, S., Linton, &. S. et al. · Psychopharmacology (2020)
Nardou, R., Sawyer, E., Song, Y. J. et al. · Nature (2023)
Doss, M. K., Považan, M., Rosenberg, M. D. et al. · Translational Psychiatry (2021)
Bogenschutz, M. P., Podrebarac, S. K., Duane, J. H. et al. · Frontiers in Pharmacology (2018)
Kamilar-Britt, P., Gordis, E. B., Earleywine, M. · Psychedelic Medicine (2023)
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