Psilocybin Therapy for Depression in Bipolar II Disorder (BAP)

An Open-Label Pilot Study Examining the Feasibility, Safety, and Effectiveness of Psilocybin Therapy for Depression in Bipolar II Disorder

The purpose of this study is to determine the safety, tolerability, and feasibility of psilocybin therapy in people with Bipolar II Disorder.

The primary goal of this study is to examine the safety, tolerability, and feasibility of psilocybin therapy in people with Bipolar II Disorder (BD II). Fourteen participants, ages 18 to 70 with clinically diagnosed BD II with active depression, in active outpatient mental health treatment, and who meet all other inclusion and exclusion criteria at screening will be enrolled. After baseline assessments, participants will engage in preparatory visits with trained facilitators, followed by an initial drug administration of oral psilocybin,supervised by the facilitators and a clinician who will conduct safety monitoring throughout. Participants will complete assessment and integration sessions with the facilitators subsequently in order to help process the experience. Participants who tolerated the first dosage may be asked to complete a second psilocybin dosing session, involving the same preparation, procedures, integration, and supervision as the first. Primary outcome measures will assess safety, tolerability, and feasibility of study procedures. Efficacy will be measured by change in depression as measured by the MADRS three weeks after the final psilocybin administration. Exploratory outcome measures will assess changes in sleep, quality of life, and therapeutic engagement.

Participants will receive one or two doses of psilocybin in a monitored setting approximately three weeks apart, with preparation sessions before and integration sessions after.

- Psilocybin administration session 10mg-25mg delivered orally with psychological support and monitoring

-Incidence, severity, and frequency of Adverse Events (AEs) including Treatment-Emergent AEs (TEAEs) and Serious AEs (SAEs)

Montgomery-Asberg Depression Rating Scale (MADRS) Each item is scored on a on a scale of 0-6 with a total score of 0-60 Higher scores correspond to worse outcomes

Measured by the treatment satisfaction questionnaire 5-item scale, plus three free response questions Higher scores representing better treatment satisfaction

Self-reported effects of psilocybin therapy on manic and/or psychotic symptoms in people with Bipolar II

Altman Self-Rating Mania Scale(ASRM-14) Each item rated on a 0 to 4 scale, with a total score of 0 to 56 Higher scores indicating greater severity of manic symptoms, with items that also measure psychosis

Young Mania Scale(YMS) 7 items are rated on a 0 to 4 scale and 4 items are rated on a 0 to 8 scale. The total score ranges from 0-60 Higher scores indicating greater severity of manic symptoms.

Columbia-Suicide Severity Rating Scale (C-SSRS) Characterizes suicidal ideation in three separate categories with a total score range from 0-25 Higher scores indicate greater severity

Patient reported effects of psilocybin therapy on depressive symptoms symptoms in people with Bipolar II (exploratory)

Quick Inventory of Depressive Symptomatology (QIDS-SR) Each item is scored on a on a scale of 0-3, with a total score of 0-27 Higher scores correspond to worse outcomes

Generalized Anxiety Disorder 7-item scale (GAD-7) Each item is rated on a scale from 0-3, with a total score of 0-21 Higher scores correspond to worse outcomes

Insomnia Severity Index (ISI) Each item is scored on a scale of 0-4 with a total score range of 0-28 Higher scores indicate greater severity in sleep disturbance

Quality of Life in Bipolar Disorder Questionnaire (QoL-BD) Each item is scored on a scale of 1-5 with a total score range of 48-240 Higher scores indicate greater quality of life

Effects of psilocybin therapy on borderline personality disorder symptoms in people with Bipolar II (exploratory)

Zanarini Rating Scale (ZRS) Each item is scored on a scale of 0-4 with a total score range of 0-30 Higher scores indicate greater severity in symptoms

Experiences in Close Relationships-Modified 16-Item Scale (ECR-M16) Each item is scored on a scale of 1-7 with a total score range of 8-126 Lower scores on each dimension of attachment anxiety and avoidance represent greater levels of attachment security

Effects of psilocybin therapy on participant-reported recovery in people with Bipolar II (exploratory)

Bipolar Recovery Questionnaire (BRQ) 36 items (visual analog scales) Higher total scores indicate a higher degree

5-Dimensional Altered States of Consciousness Rating Scale (5D-ASC) 94 items (visual analog scales) broken down into subcategories to quantify the acute subjective effects of psilocybin directly following each psilocybin administration session

Study specific Transformational Experiences Questionnaire (TEQ) Meant to quantify subjective effects of psilocybin on 1-7 scale

Inclusion Criteria: Age 18 to 70 Comfortable speaking and writing in English Diagnosis of Bipolar Disorder II with current depression Have a care partner/support person available throughout the study Able to attend all in-person visits at UCSF as well as virtual visits Having tried at least one previous medication trials for their bipolar disorder, each lasting at 6 weeks or more. Have an established mental health care provider who is seen at least once a month Exclusion Criteria: Current or previous diagnosis of Bipolar I Disorder History of schizophrenia spectrum or psychotic disorder Use of psychedelics within the past 12 months, including MDMA and Ketamine Current diagnosis of cancer Seizures that continue to the present Fear of blood or needles Regular use of medications that may have problematic interactions with psilocybin, including but not limited to antidepressants (Bupropion allowed), serotonin antagonists, some antipsychotics, dopamine agonists/antagonists, stimulants, opioids, and Lithium. A health condition that makes this study unsafe or unfeasible, determined by study physicians

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