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

Among individuals who reported a personality disorder diagnosis, psychedelic use was associated with improvements in mental health outcomes. In two observational studies, participants showed reductions in anxiety and depression symptoms lasting up to 2-3 months, with moderate to large effect sizes. Suicidal ideation decreased, and no participants moved to high risk of suicidal behavior after use. A small proportion experienced clinically significant worsening of anxiety (up to 8.2%) or depression (up to 7.1%). Transient increases in cognitive flexibility and sustained increases in cognitive reappraisal were observed, with the latter linked to reduced anxiety and depression. The findings are limited by small sample sizes and self-reported data.

Study at a glance

Abstract

Abstract Background: Personality disorders (PDs) are characterized by impairments in psychological functioning for which pharmacologic treatments have demonstrated limited efficacy. Psychedelics may offer a possible PD treatment, given preliminary evidence for their potential long-term positive effects on psychological functioning. However, little is known about safety or potential therapeutic effects of psychedelics among individuals with a PD. Therefore, we examined the effects of psychedelic use on mental health among individuals who reported a PD diagnosis. Methods: Study 1 included three prospective observational studies where 21 individuals who reported a PD diagnosis completed mental health measures (depression symptoms, anxiety, and suicidal ideation [SI]) before, 2 weeks, and 4 weeks after psychedelic use. Study 2 was a prospective observational study where 55 individuals who reported 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, all participants with high baseline risk of suicidal behavior (6.67%) became low-risk post-psychedelic use. Post-psychedelic increases in SI were rare (6.67%) with no increases to high risk of suicidal behavior. SI reduced at 4 weeks (Hedges’ g =0.52). There were few cases of clinically significant worsening anxiety (Study 1:0.0%; Study 2:7.7%-8.2%) and depression symptoms (Study 1:0.0%-7.1%; Study 2:0.0%). However, across both studies, psychedelic use was associated with reductions in anxiety (Study 1: g =-0.46–-0.57; Study 2: g =-0.52–-0.89) and depression (Study 1 g =-0.54–-0.59; Study 2 r s =.52–.57). In Study 2, there were transient increases in cognitive flexibility at 2-4 weeks ( g =0.26) and sustained increases in cognitive reappraisal up to 2-3 months ( g =0.36). Increases in cognitive reappraisal were associated with reductions in anxiety ( r =-.33) and depression ( r s =-.37). Conclusion : For individuals who reported a PD diagnosis, psychedelic use was associated with improvements in mental health outcomes. There were no clinically significant post-psychedelic increases in SI but there were a few cases of clinically significant increases 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 is needed to explore the safety and potential therapeutic effects of psychedelics among individuals with PD.