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

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 rs= .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 (rs=.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.