Bipolar II DepressionPhase 2PAT-BD-01NCT06943573
Psilocybin-Assisted Therapy for Treatment-Resistant Depression in Bipolar II Disorder
A Phase 2 study testing psilocybin (25 mg) and psilocybin 1mg micro-dose in people with Bipolar II Depression, run by Lakshmi N Yatham at 3 sites in Canada.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 19 to 65 years
- Conditions the study is for
- Bipolar II Depression
- What is being tested?
- psilocybin (25 mg) and psilocybin 1mg micro-dose
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 3 sitesCanada
- Study dates
- 15 Jun 2026to Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- You are male or female aged 19 to 65 years inclusive.
- You have a diagnosis of bipolar disorder type II, and are currently in a major depressive episode.
- 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.
- 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.
- Your current medications have been at a stable dose for two weeks prior to the dosing visit.
Who cannot join
- You have a history of psychotic symptoms.
- You have a history of seizures.
- 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).
- You have a current unstable or inadequately treated medical illness, especially cardiovascular illness, except for the current depression.
- You recently (i.e., within the past 6 weeks) started taking treatment for your acute bipolar depressive episode.
- 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).
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- You have a history of nonresponse or intolerance to psilocybin.
- You have, in the past 6 months, used any psychedelic drugs, including ketamine, LSD, or psilocybin-containing mushrooms.
- You have a history of non-response to electroconvulsive therapy.
- You are pregnant or lactating.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada3 sites, 3 recruiting
- Not yet recruiting
Department of Psychiatry, University of Ottawa, The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
Nicole Edgar, 613-737-8899 ext. 81209, nedgar@ohri.ca
Gayatri Saraf, MD
- Not yet recruiting
Department of Psychiatry, University of Toronto, University Health Network,
Toronto, Ontario, M5T 2S8
Zoe Doyle, 437-727-2252, zoe.doyle@uhn.ca
Joshua D Rosenblat, MD, MSc, FRCPC
- Recruiting
Djavad Mowafaghian Centre for Brain Health
Vancouver, British Columbia, V6T 1Z3
Vy Ngo, 604-822-3769, vy.ngo@ubc.ca
Nazlin Walji, 604-822-7294, nazlin.walji@ubc.ca
About this study
Official title: 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.
Read the 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.
- Conditions
- Bipolar II Depression
- Being tested
- psilocybin (25 mg), psilocybin 1mg micro-dose
- Keywords
- Bipolar Disorder, Mood Disorder, Psychedelic-assisted therapy, Psychedelics, Treatment resistant, Psilocybin, Depression
- Medical subject headings
- Bipolar Disorder, Mood Disorders, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
psilocybin (25 mg)Drug
Single-dose psilocybin (25 mg)-assisted therapy (PAT)
psilocybin 1mg micro-doseDrug
Single dose active placebo psilocybin-assisted therapy
| Study group | Role | What they receive |
|---|---|---|
| Active | Experimental | 25 mg psilocybin. Receives: Drug: psilocybin (25 mg) |
| Placebo | Placebo comparator | 1 mg psilocybin (micro-dose) Receives: Drug: psilocybin 1mg micro-dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in depressive symptoms
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.
Measured: Baseline to Week 3
Secondary outcomes (18)
Response Rates
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.
Measured: Week 3, Week 6, Week 12
Remission Rates
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.
Measured: Endpoint
Treatment-emergent manic/hypomanic events
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
Measured: 12 weeks
Mean change in depressive symptoms
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.
Measured: Week 6 and 12
Subjective depressive symptoms
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.
Measured: 12 weeks
Symptoms of anhedonia
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.
Measured: 12 weeks
Objective anxiety symptoms
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.
Measured: 12 weeks
Overall psychiatric status
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.
Measured: 12 weeks
Psychotic symptoms
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.
Measured: 12 weeks
Subjective cognitive functioning
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.
Measured: 12 weeks
Objective cognitive functioning
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.
Measured: 12 weeks
Sleep quality
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.
Measured: 12 weeks
Quality of Life assessed by QoL.BD
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.
Measured: 12 weeks
Daily functioning
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.
Measured: 12 weeks
Suicidal thoughts and behaviours
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.
Measured: 12 weeks
MEQ30
Psychedelic experience will be measured by the MEQ30. Scores range from 30 to 150; higher scores reflect stronger (more profound) experiences.
Measured: Dosing Visit (Day 0)
Clinician's perspective on the therapeutic relationship
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.
Measured: Baseline and Week 1
Patient's perspective on the therapeutic relationship
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.
Measured: Baseline and Week 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2025
- Study start15 Jun 2026
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar II DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, Active Placebo controlled, Randomized Clinical Trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lakshmi N Yatham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Lakshmi N Yatham, University of British Columbia
- Investigators
- Dr. Lakshmi N Yatham, Principal investigator, UBC Department of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06943573
- Sponsor's protocol ID
- H25-00074
- Acronym
- PAT-BD-01
- Status last verified
- Aug 2026
- First submitted
- 1 Apr 2025
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psilocybin-Assisted Therapy for Treatment-Resistant Depression in Bipolar II Disorder: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06943573
- Acronym / sponsor ID
- PAT-BD-01 / H25-00074
- Conditions
- Bipolar II Depression
- Keywords
- Bipolar Disorder, Mood Disorder, Psychedelic-assisted therapy, Psychedelics, Treatment resistant, Psilocybin, Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Lakshmi N YathamUniversity, hospital or other
- Study start
- 15 Jun 2026 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 24 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind, Active Placebo controlled, Randomized Clinical Trial
| Arm | Type | Receives |
|---|---|---|
| Active | Experimental | Drug: psilocybin (25 mg)25 mg psilocybin. |
| Placebo | Placebo comparator | Drug: psilocybin 1mg micro-dose1 mg psilocybin (micro-dose) |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- You are male or female aged 19 to 65 years inclusive.
- You have a diagnosis of bipolar disorder type II, and are currently in a major depressive episode.
- 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.
- 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.
- Your current medications have been at a stable dose for two weeks prior to the dosing visit.
Key exclusion criteria (10 listed)
- You have a history of psychotic symptoms.
- You have a history of seizures.
- 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).
- You have a current unstable or inadequately treated medical illness, especially cardiovascular illness, except for the current depression.
- You recently (i.e., within the past 6 weeks) started taking treatment for your acute bipolar depressive episode.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| psilocybin (25 mg)Single-dose psilocybin (25 mg)-assisted therapy (PAT) | Drug | Active |
| psilocybin 1mg micro-doseSingle dose active placebo psilocybin-assisted therapy | Drug | Placebo |
Primary outcome
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.
18 secondary outcomes
Response Rates
Time frame: Week 3, Week 6, Week 12
Remission Rates
Time frame: Endpoint
Treatment-emergent manic/hypomanic events
Time frame: 12 weeks
Mean change in depressive symptoms
Time frame: Week 6 and 12
Subjective depressive symptoms
Time frame: 12 weeks
Symptoms of anhedonia
Time frame: 12 weeks
Objective anxiety symptoms
Time frame: 12 weeks
Overall psychiatric status
Time frame: 12 weeks
Psychotic symptoms
Time frame: 12 weeks
Subjective cognitive functioning
Time frame: 12 weeks
Objective cognitive functioning
Time frame: 12 weeks
Sleep quality
Time frame: 12 weeks
Quality of Life assessed by QoL.BD
Time frame: 12 weeks
Daily functioning
Time frame: 12 weeks
Suicidal thoughts and behaviours
Time frame: 12 weeks
MEQ30
Time frame: Dosing Visit (Day 0)
Clinician's perspective on the therapeutic relationship
Time frame: Baseline and Week 1
Patient's perspective on the therapeutic relationship
Time frame: Baseline and Week 1
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Dr. Lakshmi N Yatham principal investigator
UBC Department of Psychiatry
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing psilocybin (25 mg) and psilocybin 1mg micro-dose in people with Bipolar II Depression, run by Lakshmi N Yatham at 3 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vy Ngo, B.Sc (604-822-3769, vy.ngo@ubc.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in depressive symptoms (time frame: Baseline to Week 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.