Psilocybin-Assisted Therapy for Treatment-Resistant Depression in Bipolar II Disorder (PAT-BD-01)

September 10, 2026 updated by: Lakshmi N Yatham

Psilocybin-Assisted Therapy for Treatment-Resistant Depression in Bipolar II Disorder: A Randomized Controlled Trial

This study is a 12-week (in addition to up to 30 days of screening) randomized, double-blind, placebo-controlled, parallel-group trial. The primary objective of this study is to assess the effectiveness, safety, and tolerability of single-dose psilocybin (25 mg)-assisted therapy in comparison to active placebo (1 mg micro-dose) psilocybin-assisted therapy in patients with bipolar II depression who have not responded to adequate trials with at least two first or second-line treatments for bipolar II depression (i.e. quetiapine, lithium, lamotrigine, sertraline, or venlafaxine as monotherapy or adjunctive therapy, or bupropion adjunctive therapy). The active placebo is a substance that looks identical to the study medication but contains less therapeutic ingredients, and thus is less capable of producing the transformative and meaningful aspects of psychedelic experience compared to the 25 mg dose. Participants will have a total of 11 study visits over a period of up to 16 weeks, which includes 5 therapy sessions from trained study therapists.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Bipolar disorders (BD) are lifelong conditions characterized by recurrent episodes of depression and (hypo)mania. Statistics Canada data indicate over a million Canadians are affected by this illness. Bipolar II disorder is characterised by recurrent episodes of hypomania and depression and individuals with BD-II are symptomatic about 50% of the time despite treatment. The majority of this time is spent being depressed thus there is an urgent need to develop new treatments that are safe and effective. Psilocybin, a naturally occurring psychedelic compound found in mushrooms, has been noted to result in an increase in psychological well-being in healthy volunteers as well as have antidepressant effects when administered in conjunction with psychological support. Two recent open-label pilot trials of Psilocybin-Assisted Therapy (PAT) in treatment-resistant depression, including BD-II participants, demonstrated high response rates and excellent tolerability, thereby providing strong justification for the current study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Vy Ngo, B.Sc
  • Phone Number: 604-822-3769
  • Email: vy.ngo@ubc.ca

Study Contact Backup

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6T 1Z3
        • Recruiting
        • Djavad Mowafaghian Centre for Brain Health
        • Contact:
        • Contact:
        • Principal Investigator:
          • Lakshmi N Yatham, MBBS, FRCPC, MRCPsych, MBA
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Not yet recruiting
        • Department of Psychiatry, University of Ottawa, The Ottawa Hospital
        • Principal Investigator:
          • Gayatri Saraf, MD
        • Contact:
      • Toronto, Ontario, Canada, M5T 2S8
        • Not yet recruiting
        • Department of Psychiatry, University of Toronto, University Health Network,
        • Contact:
        • Principal Investigator:
          • Joshua D Rosenblat, MD, MSc, FRCPC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. You are male or female aged 19 to 65 years inclusive.
  2. You have a diagnosis of bipolar disorder type II, and are currently in a major depressive episode.
  3. You are willing, for the entire duration of the study, to practice highly effective methods of contraception (e.g., contraceptive pills, intrauterine device or system, vasectomy and tubal ligation, or double-barrier methods of contraception) OR agree to completely abstain from heterosexual intercourse. Females who do not have childbearing potential are required to be postmenopausal for at least 1 year before the screening visit (confirmed by an FSH test) OR surgically sterile.
  4. You have sufficient English language skills to understand, consent to, and comply with study requirements, study visits, and to return to the clinic for follow-up evaluations.
  5. Your current medications have been at a stable dose for two weeks prior to the dosing visit.

Exclusion Criteria:

  1. You have a history of psychotic symptoms.
  2. You have a history of seizures.
  3. You have a first-degree relative, such as your parent, sibling, or child, with a diagnosis of a primary psychotic disorder (e.g., schizoaffective disorder, schizophrenia).
  4. You have a current unstable or inadequately treated medical illness, especially cardiovascular illness, except for the current depression.
  5. You recently (i.e., within the past 6 weeks) started taking treatment for your acute bipolar depressive episode.
  6. You recently (i.e., within the past 8 weeks) began structured psychotherapy (e.g., cognitive-behavioral therapy, interpersonal psychotherapy, family-focused therapy, or interpersonal and social rhythm therapy).
  7. You have a history of nonresponse or intolerance to psilocybin.
  8. You have, in the past 6 months, used any psychedelic drugs, including ketamine, LSD, or psilocybin-containing mushrooms.
  9. You have a history of non-response to electroconvulsive therapy.
  10. You are pregnant or lactating.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Active
25 mg psilocybin.
Drug: psilocybin (25 mg)
Single-dose psilocybin (25 mg)-assisted therapy (PAT)
Placebo Comparator: Placebo
1 mg psilocybin (micro-dose)
Drug: psilocybin 1mg micro-dose
Single dose active placebo psilocybin-assisted therapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in depressive symptoms
Time Frame: Baseline to Week 3
The Montgomery Asberg Depression Rating Scale (MADRS) will be used to measure change in depressive symptoms. Scores range from 0 to 60, and lower scores reflect better clinical outcomes.
Baseline to Week 3

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Response Rates
Time Frame: Week 3, Week 6, Week 12
Patients showing ≥50% reduction in the Montgomery Asberg Depression Rating Scale (MADRS) scores from Baseline. Scores range from 0 to 60, and lower scores reflect better clinical outcomes.
Week 3, Week 6, Week 12
Remission Rates
Time Frame: Endpoint
Defined as Montgomery Asberg Depression Rating Scale (MADRS) scores ≤ 10 and Young Mania Rating Scale (YMRS) scores ≤ 8. Scores for the MADRS range from 0 to 60, with lower scores reflecting better clinical outcomes. Scores for the YMRS range from 0 to 60, with lower scores reflecting better clinical outcomes.
Endpoint
Treatment-emergent manic/hypomanic events
Time Frame: 12 weeks
The Young Mania Rating Scale (YMRS) will be used to determine the presence of any treatment-emergent manic or hypomanic events from baseline to endpoint. Scores range from 0 to 60, and lower scores reflect better clinical outcome
12 weeks
Mean change in depressive symptoms
Time Frame: Week 6 and 12
The Montgomery Asberg Depression Rating Scale (MADRS) will be used to measure mean change in depressive symptoms. Scores range from 0 to 60, and lower scores reflect better clinical outcomes.
Week 6 and 12
Subjective depressive symptoms
Time Frame: 12 weeks
The Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) will be used to measure change in subjective depressive symptoms from baseline to endpoint. Scores on the QIDS-SR range from 0 to 27; lower scores on the QIDS-SR reflect better clinical outcomes.
12 weeks
Symptoms of anhedonia
Time Frame: 12 weeks
The Snaith-Hamilton Pleasure Scale (SHAPS) will be used to measure change in subjective symptoms of anhedonia from baseline to endpoint. Scores on the SHAPS range from 0 to 42; higher SHAPS scores indicate a reduced ability to experience pleasure and reduced capacity to feel pleasure.
12 weeks
Objective anxiety symptoms
Time Frame: 12 weeks
The Hamilton Anxiety Rating Scale (HAM-A) will be used to measure change in objective anxiety symptoms from baseline to endpoint. Scores range from 0 to 56 and lower scores reflect better clinical outcomes.
12 weeks
Overall psychiatric status
Time Frame: 12 weeks
The Clinical Global Impression - severity & change scales will be used to measure change in global severity and global improvement in symptoms from baseline to endpoint. Scores range from 3 to 42, and higher scores reflect worsening in overall psychiatric status.
12 weeks
Psychotic symptoms
Time Frame: 12 weeks
The Positive and Negative Syndrome Scale (PANSS) will be used to measure change in psychotic symptoms from baseline to endpoint. Scores range from 7 to 49, and lower scores reflect better clinical outcomes.
12 weeks
Subjective cognitive functioning
Time Frame: 12 weeks
The Cognitive Complaints in Bipolar Disorder Risk Assessment (COBRA) scale will be used to measure change in subjective cognitive functioning from baseline to endpoint. COBRA scores range from 0 to 48, and lower scores reflect better outcomes.
12 weeks
Objective cognitive functioning
Time Frame: 12 weeks
The Screen for Cognitive Impairment in Psychiatry (SCIP) will be used to measure change in objective cognitive functioning from baseline to endpoint. Higher scores reflect better outcomes.
12 weeks
Sleep quality
Time Frame: 12 weeks
The Pittsburgh Sleep Quality Index (PSQI) will be used to measure changes in sleep quality and disturbance from baseline to endpoint. Lower scores reflect better sleep quality.
12 weeks
Quality of Life assessed by QoL.BD
Time Frame: 12 weeks
The Brief Quality of Life in Bipolar Disorder (QoL.BD) will be used to measure change in quality of life from baseline to endpoint. Higher scores reflect higher quality of life.
12 weeks
Daily functioning
Time Frame: 12 weeks
The Functioning Assessment Short Test (FAST) will be used to measure change in daily functioning from baseline to endpoint. Scores range from 0 to 72 with lower scores reflecting better daily functioning.
12 weeks
Suicidal thoughts and behaviours
Time Frame: 12 weeks
The Columbia-Suicide Severity Rating Scale (C-SSRS) will be used to measure change in suicidal thoughts and behaviours from baseline to endpoint. Scores range from 0 to 37, and lower scores reflect better clinical outcomes.
12 weeks
MEQ30
Time Frame: Dosing Visit (Day 0)
Psychedelic experience will be measured by the MEQ30. Scores range from 30 to 150; higher scores reflect stronger (more profound) experiences.
Dosing Visit (Day 0)
Clinician's perspective on the therapeutic relationship
Time Frame: Baseline and Week 1
The Therapeutic Relationship will be measured with the Scale to Assess the Therapeutic Relationship - Clinician version (STAR-C). Scores range from 0 to 48 respectively; higher scores reflect better therapeutic relationships.
Baseline and Week 1
Patient's perspective on the therapeutic relationship
Time Frame: Baseline and Week 1
The Therapeutic Relationship will be measured with the Scale to Assess the Therapeutic Relationship - Patient version (STAR-P). Scores range from 0 to 48 respectively; higher scores reflect better therapeutic relationships.
Baseline and Week 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lakshmi N Yatham

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dr. Lakshmi N Yatham, UBC Department of Psychiatry

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 15, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 1, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 17, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 24, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 15, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • H25-00074

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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