ADEPT Psilocybin-Assisted Therapy With DBT for Borderline Personality Disorder

ADEPT is an open-label proof-of-concept study designed to assess the safety and tolerability of combining psilocybin-assisted therapy with Dialectical Behavior Therapy in participants with borderline personality disorder.

The study will enroll up to 18 participants who have a confirmed DSM-5 diagnosis of borderline personality disorder and are enrolled in the M Health Fairview Dialectical Behavior Therapy program. Participants must have been enrolled in DBT for at least one month and must have consistent attendance in both group and individual therapy.

The study intervention includes two 25 mg doses of psilocybin administered during supervised dosing visits. Three preparation therapy visits will occur before the first dosing visit. The first dosing visit will be followed by three integration therapy visits. A second psilocybin dosing visit will occur approximately 21 days later, followed by three additional integration therapy visits. Participants will complete a final follow-up visit at week 18, approximately 12 weeks after the second dosing visit.

Participants will continue their usual DBT program while enrolled in the study. The M Health Fairview DBT program includes weekly individual therapy, group therapy skills development, and access to phone coaching.

The primary focus of the study is safety and tolerability. Participants will be monitored during and after dosing, and adverse events, treatment-emergent adverse events, serious adverse events, suicidal ideation, challenging experiences, and psychedelic-related side effects will be assessed. Secondary outcomes will evaluate changes in borderline personality disorder symptoms, emotion regulation, depressive symptoms, quality of life, treatment credibility and expectancy, mystical experience, and continued participation in DBT after psilocybin-assisted therapy.

• Psilocybin (Drug), also known as 4-phosphoryloxy-N,N-dimethyltryptamine: Participants will receive two 25 mg doses of psilocybin during supervised dosing visits. Each dosing visit will include study therapist support for a minimum of 6 hours, with preparation and integration therapy sessions before and after dosing.
• Psilocybin-Assisted Therapy With Dialectical Behavior Therapy (Behavioral), also known as DBT + PAT: Participants will continue in the M Health Fairview Dialectical Behavior Therapy program while receiving psilocybin-assisted therapy. The study therapy sequence includes three preparation visits before the first dosing session, three integration visits after the first dosing session, a second dosing session, and three additional integration visits.

Primary outcomes

• Incidence, Severity, and Frequency of Adverse Events [Baseline through final study visit at week 18]: Safety and tolerability will be assessed by the incidence, severity, and frequency of adverse events, treatment-emergent adverse events, and serious adverse events during the study.
• Acute Suicidal Ideation After Psilocybin Dosing [Within 24 hours after each dosing visit]: Acute suicidal ideation will be assessed after each psilocybin dosing visit using the Modified Scale for Suicidal Ideation and related safety assessments.
• Challenging Experiences After Psilocybin Dosing [Integration visit 24 hours after each dosing visit]: Challenging experiences after psilocybin dosing will be assessed using the Challenging Experiences Questionnaire.
• Psilocybin-Related Side Effects [Integration visit 24 hours after each dosing visit]: Psilocybin-related side effects will be assessed using the Swiss Psychedelic Side Effects Inventory.
• Percentage of Participants Who Complete the Study [Baseline through final study visit at week 18]: Study retention will be assessed as the percentage of enrolled participants who complete the final study visit at week 18. Unit: percentage of participants
• Percentage of DBT Therapy Sessions Attended [Baseline through final study visit at week 18]: Dialectical Behavior Therapy session attendance will be assessed as the percentage of scheduled DBT therapy sessions attended during study participation. Unit: Percentage of sessions
• Percentage of Study Assessments Completed [Baseline through final study visit at week 18]: Assessment completion will be assessed as the percentage of scheduled study assessments completed during study participation. Unit: percentage of assessments

Secondary outcomes

• Change in Zanarini Rating Scale Score [Baseline to final study visit at week 18]: Borderline personality disorder symptoms will be assessed using the Zanarini Rating Scale. Change in score will be assessed from baseline to the final study visit at week 18. Higher scores indicate greater borderline personality disorder symptom severity. Unit: Points
• Change in Personality Inventory for DSM-5 Score [Baseline to final study visit at week 18]: Borderline personality disorder symptoms will be assessed using the Zanarini Rating Scale, Personality Inventory for DSM-5, Inventory of Personality Organization, and Difficulties in Emotion Regulation Scale-16.
• Change in Difficulties in Emotion Regulation Scale-16 Score [Baseline to final study visit at week 18]: Emotion regulation difficulties will be assessed using the Difficulties in Emotion Regulation Scale-16. Change in score will be assessed from baseline to the final study visit at week 18. Higher scores indicate greater emotion regulation difficulties. Unit: Points
• Change in Inventory of Personality Organization Score [Baseline to final study visit at week 18]: Personality organization will be assessed using the Inventory of Personality Organization. Change in score will be assessed from baseline to the final study visit at week 18. Higher scores indicate greater impairment in personality organization. Unit: Points
• Change in Montgomery-Asberg Depression Rating Scale Score [Baseline, week 8 after the second dose, and 3 months after the last drug dose or at DBT exit]: Depressive symptoms will be assessed using the Montgomery-Asberg Depression Rating Scale and Quick Inventory of Depressive Symptomatology. Unit: Points
• Change in Quick Inventory of Depressive Symptomatology Score [Baseline, week 8 after the second dose, and 3 months after the last drug dose or at DBT exit]: Depressive symptoms will be assessed using the Quick Inventory of Depressive Symptomatology. Change in score will be assessed from baseline to week 8 after the second dose and 3 months after the last drug dose or at DBT exit. Higher scores indicate greater depressive symptom severity. Unit: Points
• Change in Quality of Life Enjoyment and Satisfaction Questionnaire Short Form Score [Baseline to final study visit at week 18]: Quality of life will be assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form. Change in score will be assessed from baseline to the final study visit at week 18. Higher scores indicate greater quality of life enjoyment and satisfaction. Unit: points
• Credibility and Expectancy Questionnaire Credibility Score [Day before first dosing and day before second dosing]: Treatment credibility will be assessed using the Credibility and Expectancy Questionnaire. Scores will be assessed the day before the first dosing visit and the day before the second dosing visit. Higher scores indicate greater treatment credibility. Unit: Points
• Credibility and Expectancy Questionnaire Expectancy Score [Day before first dosing and day before second dosing]: Treatment expectancy will be assessed using the Credibility and Expectancy Questionnaire. Scores will be assessed the day before the first dosing visit and the day before the second dosing visit. Higher scores indicate greater treatment expectancy. Unit: Points
• Mystical Experience After Psilocybin Dosing [Integration visit immediately after each dosing visit]: Mystical experience after psilocybin dosing will be assessed using the Mystical Experience Questionnaire. Higher scores indicate greater intensity of mystical-type experience. Unit: Points
• Rate of Continued Participation in Dialectical Behavior Therapy [Through final study visit at week 18]: Continued participation in Dialectical Behavior Therapy after psilocybin-assisted therapy will be assessed as the rate of DBT participation through the final study visit at week 18. Unit: percentage of scheduled DBT sessions attended

Sex: All, ages: 25 Years to 65 Years

Inclusion Criteria:

* Confirmed DSM-5 diagnosis of borderline personality disorder using clinical records and measures used in the M Health Fairview DBT program
* Enrolled in the M Health Fairview DBT program for at least one month, with consistent attendance in group and individual therapy
* Age 25 to 65 years
* Able to speak and understand English
* Ability to complete all protocol-required assessment tools without assistance or alteration to copyrighted assessments
* Ability to comply with all study visits
* Stated willingness to comply with all study procedures and avoid changes to current treatments for the duration of the study
* If of childbearing potential, use of an acceptable birth control method, including abstinence

Exclusion Criteria:

* Refusal to give informed consent
* History of bipolar affective disorder type I or II, schizophrenia, psychosis, delusions, paranoia, schizoaffective disorder, or substance use disorder within the past 12 months
* First- or second-degree relative with schizophrenia or any other psychotic disorder
* Active suicidal ideation with at least some intent and/or plan, defined as a current score of 4 or 5 on the C-SSRS
* History of suicide attempt in the last 6 months
* Comorbid autism
* Pregnant or may have reason to believe they are pregnant
* Pre-existing valvular heart disease or pulmonary hypertension
* Active primary PTSD diagnosis
* Psychiatric or other condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
* Any medical or psychiatric disorder, disease, condition, injury, symptom, or circumstance that may reduce ability to fulfill study requirements, adversely impact data integrity or validity, or pose increased risk during study participation
* Children
* Prisoners
* Adults lacking capacity to consent or adults with diminished or fluctuating capacity to consent
* Non-English speakers
* Individuals unable to read
* Employees of the researcher
* Students of the researcher
* Active members of the military or DoD personnel

• Ziad Nahas, MD, MSCR, Principal investigator, University of Minnesota
• Devin H Hanson, PhD, LP, Study director, University of Minnesota