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Review
. 2025 Jul 1:272:110413.
doi: 10.1016/j.neuropharm.2025.110413. Epub 2025 Mar 11.

Exploring serotonergic psychedelics as a treatment for personality disorders

Brennan M Carrithers  1 , Daniel E Roberts  2 , Brandon M Weiss  3 , Jacob D King  4 , Robin L Carhart-Harris  5 , Alexandra R Gordon  2 , Broc A Pagni  2 , Miltiadis Moreau  6 , Stephen Ross  2 , Richard J Zeifman  7
Affiliations
Review

Exploring serotonergic psychedelics as a treatment for personality disorders

Brennan M Carrithers et al. Neuropharmacology. .

Abstract

Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy could hold potential for addressing core features of PDs through shared mechanisms of personality modulation. Although historical literature and observational studies suggest the potential clinical utility of psychedelics in treating PDs, rigorous research is lacking, and individuals with PDs are often excluded from modern psychedelic therapy trials. In the present review, we first discuss research on the effects of psychedelics in individuals with a PD through the conventional lens of the Diagnostic and Statistical Manual of Mental Disorders (5th ed., text rev.; DSM-5-TR) categorical model. Next, using the dimensional DSM Alternative Model of Personality Disorders (DSM-AMPD) as a framework, we examine how psychedelics may affect self-functioning, interpersonal functioning, and pathological personality traits. We conclude by discussing the clinical relevance of psychedelic therapy as a treatment for personality pathology, including safety considerations, gaps and limitations, and recommendations for approaching psychedelic therapy within these more complex clinical populations.

Keywords: Personality disorders; Personality traits; Psilocybin-assisted therapy; Psychedelics; Psychopharmacology; Psychotherapy.

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Conflict of interest statement

Declaration of competing interest BMC, BMW, JDK, BAP, MM, and ARG report no competing interests. DER has received financial compensation as an independent contractor from Fluence International, Inc. RCH acts as an advisor to Entheos Lab, Mindstate, Maya Health, Osmind, Beckley Psytech, TRYP Therapeutics,Journey Collab, Journey Space, and Usona Institute. SR is the Director of NYU Langone Center for Psychedelic Medicine Research Training Program, which is funded by MindMed. SR currently receives, or has received in the past 36 months, grant support for clinical research from the National Institute on Drug Abuse, National Cancer Institute, Heffter Research Institute, Usona Institute, Council on Spiritual Practices, Multidisciplinary Association of Psychedelic Studies and Reset Pharmaceuticals. RJZ received funding from the NYU Langone Psychedelic Medicine Research Training program funded by MindMed and the Canadian Institutes of Health Research (Grant Number: 202110MFE-472921-HTB-272687). None of these organization were involved in the design, execution, interpretation, or communication of this publication.