Clin Neuropharmacol. 2026 Apr 1. doi: 10.1097/WNF.0000000000000683. Online ahead of print.
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.
PMID:41973961 | DOI:10.1097/WNF.0000000000000683
