A Phase 2 interventional study of psilocybin (25 mg) and psilocybin 1mg micro-dose in Bipolar II Depression, sponsored by Lakshmi N Yatham. Recruiting at 3 sites in Canada. Open to participants aged 19 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-09-15.
Sponsored by Lakshmi N Yatham · Phase 2, Interventional, and Treatment
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.
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.
1,683 studies on the registry are indexed under Bipolar Disorder; 266 are open to participants now.
This study's planned enrollment of 90 is above the median of 64 across 1,279 interventional studies indexed under Bipolar Disorder.
Browse Bipolar Disorder studies →Lakshmi N Yatham is the lead sponsor of 3 studies on the registry; 1 is open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
25 mg psilocybin.
Drug: psilocybin (25 mg)
1 mg psilocybin (micro-dose)
Drug: psilocybin 1mg micro-dose
Single-dose psilocybin (25 mg)-assisted therapy (PAT)
Single dose active placebo psilocybin-assisted therapy
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.
Time frame: Baseline to Week 3
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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 12 weeks
MEQ30
Psychedelic experience will be measured by the MEQ30. Scores range from 30 to 150; higher scores reflect stronger (more profound) experiences.
Time frame: 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.
Time frame: 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.
Time frame: Baseline and Week 1
Plan to share: No
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Studies of the drug tested here: Psilocybin