NCT06943573

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

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

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 90 (estimated)
• Sponsor: Lakshmi N Yatham · Academic / Other
• Sex: All
• Age: 19 Years – 65 Years
• Healthy volunteers: Not accepted

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.

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

Interventions

Type	Name	Description
DRUG	psilocybin (25 mg)	Single-dose psilocybin (25 mg)-assisted therapy (PAT)
DRUG	psilocybin 1mg micro-dose	Single dose active placebo psilocybin-assisted therapy

Timeline

• Start date: 2025-10-01
• Primary completion: 2028-12-01
• Completion: 2028-12-01
• First posted: 2025-04-24
• Last updated: 2025-08-27

Locations

3 sites across 1 country: Canada