Anxiety DisordersDepressive DisordersSuicidalityPersonality DisordersInterpersonal Functioning & Social Connectedness

The Effect of Psychedelics on Individuals with a Personality Disorder: Results from two Prospective Cohort Studies

In two prospective cohort studies of people with a diagnosed personality disorder, psychedelic use was associated with moderate reductions in anxiety and depressive symptoms and increases in cognitive reappraisal, with transient improvements in cognitive flexibility. Clinically significant elevations in suicidal behaviour were rare, though several participants experienced worsened anxiety or depression; findings are limited by small samples, self‑report data and lack of differentiation between PD subtypes.

Authors

  • Richard Zeifman
  • Robin Carhart-Harris
  • Hannes Kettner

Published

Research Square
individual Study

Abstract

Background

Personality disorders (PDs) are characterized by impairments in psychological functioning for which pharmacologic treatments have demonstrated limited efficacy. Psychedelics may offer a potential PD treatment, given support for their potential enduring positive effects on psychological functioning. However, little is known about the safety or therapeutic effects of psychedelics among individuals with a PD. Therefore, we examined the effects of psychedelic use on mental health among individuals with a PD.

Methods

Study 1 included three prospective observational studies where 21 individuals with a PD diagnosis completed mental health measures (depressive symptoms, anxiety, and suicidal ideation [SI]) before, 2 weeks (except SI), and 4 weeks after psychedelic use. Study 2 was a prospective observational study in which 55 individuals with a PD diagnosis completed mental health measures (anxiety, depressive symptoms, cognitive flexibility, expressive suppression, and cognitive reappraisal) before, 2-4 weeks, and 2-3 months after psychedelic use.

Results

In Study 1, elevations in SI were rare (6.67%) with no elevations to high risk of suicidal behavior post-psychedelic use. All participants with high baseline risk of suicidal behavior (6.67%) were at low-risk post-psychedelic use. SI reduced at 4 weeks (Hedges’ g =0.52). There were several cases of increased anxiety (Study 1: 13.6%-25.0%; Study 2: 16.3%-11.5%) and clinically significant worsening of depression symptoms (Study 1: 14.3%-14.2%; Study 2: 10.0%-8.0%). Across both studies, psychedelic use was associated with reductions in anxiety (Study 1: g =-.46–-.57; Study 2 g =-.52–-.89) and depression (Study 1 g =-.54–-0.59; Study 2 r s = .52–.57) . In Study 2, there were transient increases in cognitive flexibility at 2-4 weeks ( g =.26) and sustained increases in cognitive reappraisal up to 2-3 months ( g =.36). Increases in cognitive reappraisal were associated with reductions in anxiety ( r =.33) and depression ( r s =.37). Conclusion : For individuals with PD, psychedelic use was associated with improvements in psychological functioning. There were no clinically significant elevations in SI and several cases of elevations in anxiety and depression severity. The studies are limited by a small sample size, self-reported data, and lack of differentiation between PDs. Further research should explore the safety and potential therapeutic effects of psychedelics among individuals with PD.

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Research Summary of 'The Effect of Psychedelics on Individuals with a Personality Disorder: Results from two Prospective Cohort Studies'

Introduction

Personality disorders (PDs) are enduring patterns of maladaptive intra- and interpersonal functioning that frequently co-occur with depression, anxiety, suicidality, emotion-regulation problems and impaired cognitive flexibility. Existing psychotherapies and adjunctive pharmacotherapies show only modest effectiveness for many PD presentations, and regulatory-approved pharmacologic treatments specific to PDs are lacking. Classic psychedelics (for example psilocybin, LSD, DMT/ayahuasca, mescaline) act primarily at the 5-HT2A receptor and, in therapeutic contexts, have shown promise for a range of psychiatric disorders and for improving constructs relevant to PD pathology such as emotion regulation and cognitive flexibility. Despite this, people with PDs are frequently excluded from psychedelic-assisted therapy (PAT) trials, leaving a gap in knowledge about safety and therapeutic effects for this population. Gordon and colleagues set out to address that gap by analysing prospective data from two naturalistic cohort studies of psychedelic use. The investigators aimed to characterise short- to medium-term changes in suicidality, depressive symptoms, anxiety, cognitive flexibility and emotion-regulation (expressive suppression and cognitive reappraisal) among people who self-reported a PD diagnosis and who used psychedelics outside a controlled clinical trial. The paper reports two analyses: Study 1 pooled data from three online cohort studies of classic psychedelic use and focused on suicidal ideation, depression and trait anxiety up to 4 weeks post-use, while Study 2 used a larger prospective cohort of planned psilocybin use to examine depressive symptoms, trait anxiety, cognitive flexibility and emotion-regulation up to 2–3 months post-use.

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