NCT07281352

RCT of Psilocybin-assisted CBT for Depression

Psilocybin-Assisted Cognitive Behavioral Therapy for Depression

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: University of California, Los Angeles · Academic / Other
• Sex: All
• Age: 21 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

The primary objectives of this clinical investigation are to (1) determine the acceptability and feasibility of joining psilocybin-assisted therapy with cognitive-behavioral therapy (PA-CBT) for patients with depression, (2) optimize CBT to most effectively integrate the psilocybin experience with psychotherapy and (3) examine the clinical benefit of psilocybin as an adjunct to cognitive-behavioral therapy (CBT) for major depressive disorder. This study is a randomized, two-arm, fixed dose trial that will test the feasibility, acceptability, and participant and therapist adherence to PA-CBT. Both treatment arms will receive two doses of psilocybin (10mg and then 25mg, separated by one month). In Phase II, participants will be randomized (1:1) to either a 12-session PA-CBT or a 6-session standard psilocybin-assisted therapy (PAT) condition (3 hours of preparation plus 3 hours of supportive therapy integration following the psilocybin experiences).

Conditions

• Major Depressive Diorder

Interventions

Type	Name	Description
DRUG	Psilocybin (drug)	Participants will receive two doses of psilocybin (10mg, 25mg).
BEHAVIORAL	cognitive behavioral therapy	Twelve total sessions of therapy, including manualized cognitive behavioral therapy for major depressive disorder, including psychoeducation about depression, cognitive skills, and behavioral skills as well as preparation for psilocybin.
BEHAVIORAL	Minimal supportive therapy	Six total therapy sessions. Preparation for psilocybin in the first three sessions plus supportive, nondirective psychotherapy in the final three sessions.

Timeline

• Start date: 2026-01-05
• Primary completion: 2027-11-30
• Completion: 2027-11-30
• First posted: 2025-12-15
• Last updated: 2026-02-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study