Research Citations

Selected papers on buprenorphine, BPD, the endogenous opioid system, and related mechanisms.

Buprenorphine is an opioid medication. Combining it with benzodiazepines, alcohol, or other central nervous system depressants increases the risk of respiratory depression. See the safety section on the main page.

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Borderline Personality Disorder & the Endogenous Opioid System

Borderline Personality Disorder: A Dysregulation of the Endogenous Opioid System? (2010)

Proposes that BPD symptoms stem from imbalance in the brain’s internal opioid system, affecting attachment, pain, distress tolerance, and emotional stability.

DOI: 10.1037/a0018095

The Interpersonal Dimension of Borderline Personality Disorder: Toward a Neuropeptide Model (2010)

Explores attachment, distress, and affective instability through the lens of endogenous opioids and neuropeptide systems.

DOI: 10.1176/appi.ajp.2009.09050744

An Opioid Deficit in Borderline Personality Disorder: Self-Cutting, Substance Abuse, and Social Dysfunction (2010)

Proposes that many core features of BPD—such as distress intolerance, interpersonal instability, self-injury, and substance use—can be understood as attempts to temporarily correct an underlying endogenous opioid deficit, providing short-lived relief from emotional pain and emptiness.

DOI: 10.1176/appi.ajp.2010.10040634
Some of the studies below use specialized neuroimaging or genetic methods; summaries are provided for accessibility.

Dysregulation of regional endogenous opioid function in borderline personality disorder (2010)

Using PET imaging, this study found that people with BPD show higher baseline μ-opioid receptor availability, interpreted by the authors as reflecting lower baseline endogenous opioid activity, along with abnormal opioid system responses during emotional distress. These findings provide direct biological evidence that the brain’s internal pain- and attachment-buffering system is dysregulated in BPD.

DOI: 10.1176/appi.ajp.2010.09091348

Differential methylation of OPRK1 in borderline personality disorder is associated with childhood trauma (2024)

This study found trauma-associated epigenetic changes in OPRK1, the gene encoding the κ-opioid receptor, in people with BPD. The findings suggest long-term, trauma-linked alterations in the stress-related opioid system, which is known to drive dysphoria and aversive emotional states.

DOI: 10.1038/s41380-024-02628-z

Taken together, these findings support a model in which borderline personality disorder involves both insufficient baseline μ-opioid signaling (contributing to chronic emptiness and social pain) and trauma-linked overactivation of the κ-opioid stress system (contributing to dysphoria, shutdown, and self-harm urges under stress). This dual dysregulation helps explain why treatments targeting only one pathway may be insufficient, and why medications like buprenorphine—which partially activate μ-opioid receptors while antagonizing κ-opioid receptors—are mechanistically well-suited to address core features of the disorder.

Buprenorphine for Depression & Suicidality

Safety, Tolerability, and Clinical Effect of Low-Dose Buprenorphine for Treatment-Resistant Depression in Midlife and Older Adults (2014)

Demonstrates that low-dose buprenorphine improves mood in people whose depression did not respond to standard treatment options.

DOI: 10.4088/JCP.13m08725

Ultra-Low-Dose Buprenorphine as a Time-Limited Treatment for Severe Suicidal Ideation: A Randomized Controlled Trial (2015)

Shows rapid (days-scale) reduction in severe suicidal thinking using ultra-low doses of buprenorphine.

DOI: 10.1176/appi.ajp.2015.15040535

Use of Buprenorphine in Treatment of Refractory Depression — A Review of Current Literature (2017)

Summarizes emerging evidence for buprenorphine’s antidepressant and anti-suicidal effects, including partial mu-agonism and kappa-antagonism mechanisms.

DOI: 10.1016/j.ajp.2017.01.015

Case Reports Related to BPD

The Use of Buprenorphine/Naloxone to Treat Borderline Personality Disorder: A Case Report (2022)

Documents a patient with BPD who showed substantial improvement in emotional regulation and suicidality after treatment with buprenorphine/naloxone (Suboxone).

DOI: 10.1186/s40479-022-00181-1

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