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.

Study Overview

• Status: Active, not recruiting
• Conditions: Bipolar II Disorder
• Intervention / Treatment: Drug: Psilocybin therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Exclusion Criteria:

• Current or previous diagnosis of Bipolar I Disorder
• History of schizophrenia spectrum or psychotic disorder
• Use of psychedelics within the past 6 months, including MDMA
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin therapy; 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.	Drug: Psilocybin therapy; - Psilocybin administration session 10mg-25mg delivered orally with psychological support and monitoring; Other Names: 4-phosphoryloxy-N,N-dimethyltryptamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of psilocybin therapy for depression in BD II	-Incidence, severity, and frequency of Adverse Events (AEs) including Treatment-Emergent AEs (TEAEs) and Serious AEs (SAEs)	Baseline to 3 months following last drug dose
Recruitment rate	-Measured as a percentage of participants who were contacted for pre-screening and consented.	Baseline to 3 months following last drug dose
Retention rate	-Measured as a percentage of participants who began and completed treatment.	Baseline to 3 months following last drug dose
Clinician-reported effects of psilocybin therapy on depressive symptoms in people with Bipolar II	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	Baseline to 3 weeks following last drug dose
Treatment Satisfaction of study procedures	Measured by the treatment satisfaction questionnaire; 5-item scale, plus three free response questions; Higher scores representing better treatment satisfaction	Baseline to 3 months following last drug dose
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	Baseline to 11 days following each drug dose
Clinician-reported effects of psilocybin therapy on mania symptoms in people with Bipolar II	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.	Baseline to 3 months following each drug dose
Clinician-reported effects of psilocybin therapy on suicidality symptoms in people with Bipolar II	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	Baseline to 3 months following last drug dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Baseline to 3 months following last drug dose
Effects of psilocybin therapy on anxiety symptoms in people with Bipolar II (exploratory)	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	Baseline to 3 months following last drug dose
Effects of psilocybin therapy on sleep quality in people with Bipolar II (exploratory)	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	Baseline to 3 months following last drug dose
Effects of psilocybin therapy on quality of life in people with Bipolar II (exploratory)	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	Baseline to 3 months following last drug dose
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	Baseline to 3 months following last drug dose
Effects of psilocybin therapy on adult attachment in people with Bipolar II (exploratory)	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	Baseline to 3 months following last drug dose
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	Baseline to 3 months following last drug dose
Subjective effects of psilocybin therapy in people with Bipolar II	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	Baseline to 3 months following last drug dose
Subjective effects of psilocybin therapy in people with Bipolar II	Study specific Transformational Experiences Questionnaire (TEQ); Meant to quantify subjective effects of psilocybin on 1-7 scale	3 weeks following last drug dose

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Investigators: Principal Investigator: Joshua D Woolley, MD,PhD, University of California, San Francisco; Study Director: David Guard, PhD, San Francisco State University

Publications and helpful links

General Publications

• Grande I, Berk M, Birmaher B, Vieta E. Bipolar disorder. Lancet. 2016 Apr 9;387(10027):1561-1572. doi: 10.1016/S0140-6736(15)00241-X. Epub 2015 Sep 18.
• Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.
• Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.
• Carhart-Harris RL, Bolstridge M, Day CMJ, Rucker J, Watts R, Erritzoe DE, Kaelen M, Giribaldi B, Bloomfield M, Pilling S, Rickard JA, Forbes B, Feilding A, Taylor D, Curran HV, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl). 2018 Feb;235(2):399-408. doi: 10.1007/s00213-017-4771-x. Epub 2017 Nov 8.
• Szmulewicz AG, Angriman F, Samame C, Ferraris A, Vigo D, Strejilevich SA. Dopaminergic agents in the treatment of bipolar depression: a systematic review and meta-analysis. Acta Psychiatr Scand. 2017 Jun;135(6):527-538. doi: 10.1111/acps.12712. Epub 2017 Mar 3.

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2022
• Primary Completion (Actual): August 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: September 14, 2021
• First Submitted That Met QC Criteria: September 28, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Actual): September 25, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Depression; Safety; Bipolar; Psilocybin; Bipolar II; Psychedelic; Psilocybin Therapy
• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Hallucinogens; Psilocybin; N,N-Dimethyltryptamine
• Other Study ID Numbers: 20-32789

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No