An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder
This open-label pilot study (n=9) tested a single dose of psilocybin in adults with borderline personality disorder and major depressive disorder. Depressive symptoms improved over four weeks, but borderline personality disorder symptoms did not change significantly.
Authors
- Grant, J. E.
- Boutouis, S.
- O’Brien, M.
Published
Abstract
Objectives
Borderline personality disorder (BPD) is often comorbid with major depressive disorder (MDD), and there has been a suggestion in the literature that this comorbidity may interfere with MDD treatment response. Our objective was to conduct a pilot study of psilocybin in adults with BPD and MDD.
Methods
Adults aged 18 to 65 years with a DSM-5 diagnosis of MDD and BPD were enrolled in an open-label pilot study of a single dose of psilocybin. Assessments were conducted 1 week before dosing (baseline), on the dosing day (visit 2), and at 1, 2, and 4 weeks postdosing. The co-primary outcome measures were changes in depressive and BPD symptoms from baseline to study endpoint, and we used a paired-samples t test to examine changes in symptoms.
Results
Nine participants (4 males; mean age=31.3 y) with MDD and BPD were enrolled. MDD symptoms significantly changed from baseline to visit 5: baseline (M=28.56, SD=4.53) and final visit (M=17.22, SD=10.39); t(8)=-4.217, P=0.003; Cohen d=1.41. BPD scores did not significantly change from baseline to study endpoint.
Conclusions
This small open-label study resulted in statistically significant improvement in MDD symptoms but not for BPD symptoms. These findings, which await larger clinical trials, suggest that BPD does not appear to interfere with response to depressive symptoms.
Research Summary of 'An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder'
Blossom's Take
Unlike the generally positive effects on depressive disorders, this study found no such impact on co-occurring borderline (BPD) in this small patient population. Still, the authors argue that BPD may not need to be an exclusion criteria in depression studies with psilocybin.
Introduction
Borderline personality disorder (BPD) commonly co-occurs with major depressive disorder (MDD), and earlier research has suggested that BPD may make depression harder to treat. The authors note that psilocybin has shown promise for depression, but it was unclear whether people with BPD and MDD would benefit similarly, particularly because BPD symptoms themselves might change differently or interfere with antidepressant response. Grant and colleagues therefore set out to conduct a pilot open-label study of a single dose of psilocybin in adults with both BPD and MDD. Their main aim was to examine whether depressive symptoms and BPD symptoms changed after treatment, and whether co-occurring BPD seemed to limit any antidepressant effect. The study was exploratory and designed to generate early safety and efficacy signals for future trials.
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Study Details
- Study Typeindividual
- Journal
- Compound
- Topics
- APA Citation
Grant, J. E., Boutouis, S., O’Brien, M., Avila, L., Neelapu, M., & Ehsan, D. (2026). An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder. Clinical Neuropharmacology. https://doi.org/10.1097/wnf.0000000000000683
References (2)
Papers cited by this study that are also in Blossom
Fineberg, S. K., Choi, E. Y., Shapiro-Thompson, R. et al. · Neuropsychopharmacology (2023)
Goodwin, G. M., Aaronson, S. T., Alvarez, O. et al. · New England Journal of Medicine (2022)
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