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

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.

NCT Number	NCT06943573
Lead Sponsor	Lakshmi N Yatham
Conditions	Bipolar II Depression
Enrollment	90 participants
Start Date	2026-05-01
Primary Completion	2028-12 (estimated)
Study Completion	2028-12 (estimated)
Updated on ClinicalTrials.gov	2026-05-01