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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 via PubMed

Summary

AI-generated from the abstract

A small open-label pilot study tested a single dose of psilocybin in nine adults aged 18 to 65 with both borderline personality disorder (BPD) and major depressive disorder (MDD). Depressive symptoms significantly improved from baseline to four weeks after dosing, with average scores dropping from 28.56 to 17.22. However, BPD symptoms did not show a significant change. The findings suggest that BPD may not interfere with psilocybin's effect on depressive symptoms, but larger clinical trials are needed.

Study at a glance

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 finding 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.

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