An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder

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.

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Publication Details

Journal
Clinical Neuropharmacology
Published
2026-04-01
DOI
https://doi.org/10.1097/wnf.0000000000000683
Primary Topic
Psychedelics and Drug Studies
Type
article
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article

An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder

Jon E. Grant, Sophia Boutouis, Laurie Avila, Megha Neelapu et al.
Clinical Neuropharmacology
Psychedelics and Drug Studies
article

An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder

Jon E. Grant, Sophia Boutouis, Laurie Avila, Megha Neelapu, Margaret O’Brien, Dustin Ehsan
article en

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.

Clinical Neuropharmacology
Oxford University Press (United Kingdom) (GB), University of Chicago (US), Los Angeles Clinical Trials (US), Artistic Realization Technologies (US)
Openalex Percentile: Top 16%
Psychedelics and Drug Studies
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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, et al. · Clinical Neuropharmacology (2026) | TGRS Research Map | TGRS