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 DOI: 10.1097/wnf.0000000000000683 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label pilot study Peer reviewed |
|---|---|
| Sample size | 9 |
| Population | Adults aged 18 to 65 years with DSM-5 diagnoses of major depressive disorder and borderline personality disorder |
| Intervention | Psilocybin |
| Dose | single dose |
| Duration | 4-week study period with assessments at baseline, dosing day, and 1, 2, and 4 weeks postdosing |
| Topics | Depression Psilocybin |
| Keywords | Borderline personality Treatment |
| Key points | A single dose of psilocybin significantly improved depressive symptoms but not borderline personality disorder symptoms in adults with both conditions. |
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.
Comparable studies
Other non-randomized and open-label trials on psilocybin for depression, most cited first.