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

NCT06943573 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: H25-00074
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Bipolar II Depression

Keywords

Bipolar Disorder; Mood Disorder; Psychedelic-assisted therapy; Psychedelics; Treatment resistant; Psilocybin; Depression

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to Week 3

Secondary Outcomes (18)

• Response Rates

  Week 3, Week 6, Week 12

• Remission Rates

  Endpoint

• Treatment-emergent manic/hypomanic events

  12 weeks

• Mean change in depressive symptoms

  Week 6 and 12

• Subjective depressive symptoms

  12 weeks

Study Arms (2)

Active

EXPERIMENTAL

25 mg psilocybin.

Drug: psilocybin (25 mg)

Placebo

PLACEBO COMPARATOR

1 mg psilocybin (micro-dose)

Drug: psilocybin 1mg micro-dose

Interventions

psilocybin (25 mg) DRUG

Single-dose psilocybin (25 mg)-assisted therapy (PAT)

Active

psilocybin 1mg micro-dose DRUG

Single dose active placebo psilocybin-assisted therapy

Placebo

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• You have a history of psychotic symptoms.
• You have a history of seizures.
• 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).
• 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.

Sponsors & Collaborators

• Lakshmi N Yatham: lead

Study Sites (3)

Djavad Mowafaghian Centre for Brain Health

Vancouver, British Columbia, V6T 1Z3, Canada

Location

Department of Psychiatry, University of Ottawa, The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

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

Toronto, Ontario, M5T 2S8, Canada

Location

MeSH Terms

Conditions

Bipolar Disorder; Mood Disorders; Depression

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Dr. Lakshmi N Yatham

  UBC Department of Psychiatry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vy Ngo, B.Sc

CONTACT

604-822-3769; vy.ngo@ubc.ca

Nazlin Walji, B.Sc, CCRC

CONTACT

604-822-7294; nazlin.walji@ubc.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study Therapist
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Double-blind, Active Placebo controlled, Randomized Clinical Trial

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 24, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)