Psilocybin-Assisted Therapy for Treatment-Resistant Depression in Bipolar II Disorder

Last updated: April 29, 2026
Sponsor: Lakshmi N Yatham
Overall Status: Active - Not Recruiting

Phase

3

Condition

Bipolar Disorder

Depression

Mood Disorders

Treatment

psilocybin 1mg micro-dose

psilocybin (25 mg)

Clinical Study ID

NCT06943573
H25-00074
  • Ages 19-65
  • All Genders

Study 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 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.

Eligibility Criteria

Inclusion

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 majordepressive episode.

  3. You are willing, for the entire duration of the study, to practice highly effectivemethods of contraception (e.g., contraceptive pills, intrauterine device or system,vasectomy and tubal ligation, or double-barrier methods of contraception) OR agreeto completely abstain from heterosexual intercourse. Females who do not havechildbearing potential are required to be postmenopausal for at least 1 year beforethe screening visit (confirmed by an FSH test) OR surgically sterile.

  4. You have sufficient English language skills to understand, consent to, and complywith study requirements, study visits, and to return to the clinic for follow-upevaluations.

  5. Your current medications have been at a stable dose for two weeks prior to thedosing visit.

Exclusion

Exclusion Criteria:

  1. You have a history of psychotic symptoms.

  2. You have a history of seizures.

  3. You have a current unstable or inadequately treated medical illness, especiallycardiovascular illness, except for the current depression.

  4. You recently (i.e., within the past 6 weeks) started taking treatment for your acutebipolar depressive episode.

  5. 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).

  6. You have a history of nonresponse or intolerance to psilocybin.

  7. You have, in the past 6 months, used any psychedelic drugs, including ketamine, LSD,or psilocybin-containing mushrooms.

  8. You have a history of non-response to electroconvulsive therapy.

  9. You are pregnant or lactating.

Study Design

Total Participants: 90
Treatment Group(s): 2
Primary Treatment: psilocybin 1mg micro-dose
Phase: 3
Study Start date:
May 01, 2026
Estimated Completion Date:
December 31, 2028

Study 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.

Connect with a study center

  • Djavad Mowafaghian Centre for Brain Health

    Vancouver, British Columbia V6T 1Z3
    Canada

    Site Not Available

  • Djavad Mowafaghian Centre for Brain Health

    Vancouver 6173331, British Columbia 5909050 V6T 1Z3
    Canada

    Site Not Available

  • Department of Psychiatry, University of Ottawa, The Ottawa Hospital

    Ottawa, Ontario K1H 8L6
    Canada

    Site Not Available

  • Department of Psychiatry, University of Toronto, Centre for Addiction and Mental Health

    Toronto, Ontario M6J 1H4
    Canada

    Site Not Available

  • Department of Psychiatry, University of Toronto, University Health Network,

    Toronto, Ontario M5T 2S8
    Canada

    Site Not Available

  • Department of Psychiatry, University of Ottawa, The Ottawa Hospital

    Ottawa 6094817, Ontario 6093943 K1H 8L6
    Canada

    Site Not Available

  • Department of Psychiatry, University of Toronto, University Health Network,

    Toronto 6167865, Ontario 6093943 M5T 2S8
    Canada

    Site Not Available

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