An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder.
Jon E Grant, Sophia Boutouis, Margaret O'brien, Laurie Avila, Megha Neelapu, Dustin Ehsan
Clinical neuropharmacology April 1, 2026 Peer reviewed DOI: 10.1097/wnf.0000000000000683 via PubMed
Summary
In a pilot study, a single dose of psilocybin led to a significant reduction in major depressive disorder (MDD) symptoms among adults with comorbid borderline personality disorder (BPD), with scores dropping from an average of 28.56 at baseline to 17.22 at the final visit. However, BPD symptoms did not show significant change. The results indicate that having BPD does not seem to hinder the treatment response for depressive symptoms.
Study at a glance
| Design | open-label pilot study |
|---|---|
| Sample size | 9 |
| Population | adults aged 18 to 65 years with comorbid major depressive disorder and borderline personality disorder |
| Key finding | Psilocybin treatment resulted in a significant improvement in MDD symptoms but did not significantly affect BPD symptoms. |
Abstract
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. 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. 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. 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.