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

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.