RCT of Psilocybin-assisted CBT for Depression

NCT ID: NCT07281352

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-05
• Study Completion Date: 2027-11-30

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Experimental: Psilocybin + CBT

Participants will receive 12 sessions of cognitive-behavioral therapy (CBT) along with two psilocybin-drug sessions -- the first following the third CBT session (10mg of psilocybin, taken orally) and the second following the sixth CBT session (25mg of psilocybin, taken orally).

Group Type: EXPERIMENTAL

Psilocybin (drug)

Intervention Type: DRUG

Participants will receive two doses of psilocybin (10mg, 25mg).

cognitive behavioral therapy

Intervention Type: BEHAVIORAL

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.

Psilocybin + Minimal supportive therapy

Participants will receive 6 sessions of supportive, non-directive therapy along with two psilocybin-drug sessions -- the first following the third therapy session (10mg of psilocybin, taken orally) and the second following the fourth therapy session (25mg of psilocybin, taken orally).

Group Type: ACTIVE_COMPARATOR

Psilocybin (drug)

Intervention Type: DRUG

Participants will receive two doses of psilocybin (10mg, 25mg).

Minimal supportive therapy

Intervention Type: BEHAVIORAL

Six total therapy sessions. Preparation for psilocybin in the first three sessions plus supportive, nondirective psychotherapy in the final three sessions.

Interventions

Psilocybin (drug)

Participants will receive two doses of psilocybin (10mg, 25mg).

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Ages 21-60,

• Able to swallow capsules,
• Patients with a current major depressive episode or a history of major depressive episodes based on the DSM-5 criteria (American Psychiatric Association, 2013),
• Active current depressive symptoms (i.e., scores >16 on the Hamilton-Depression Rating Scale (HAM-D) covering the prior 2 weeks; Hamilton, 1986),
• Have an identified support person who can pick up the individual from UCLA Semel Institute and drive individual home following psilocybin sessions,
• For women of child-bearing potential - using one form of highly effective contraception (e.g., oral contraceptive pill) and willingness to continue contraceptive use for duration of study
• Patient has been medically cleared for the study by a physician.

Exclusion Criteria

• A personal or family history (first or second-degree) of psychosis or bipolar disorder

• Resting blood pressure above 140 systolic, 90 diastolic (averaged across four separate measurements)
• Meeting criteria for a DSM-5 cluster B personality disorder (narcissistic, histrionic, borderline, antisocial personality disorder),
• Active suicidality (as indicated by a 3 or greater on item 3 of the HAM-D) or other psychiatric disturbance requiring acute treatment
• Current use of antidepressants or other serotonergic-affecting substances (e.g., St. John's Wort and 5-hydroxytryptophan),
• Currently receiving cognitive behavioral therapy,
• Any of the following cardiovascular conditions: uncontrolled hypertension, coronary artery disease, congenital long QT syndrome, cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction, tachycardia, artificial heart valve, a clinically significant screening ECG abnormality, or any other significant cardiovascular condition
• A history of stroke or Transient Ischemic Attack (TIA)
• Epilepsy or history of seizures
• Insulin-dependent diabetes
• Meeting criteria for a DSM-5 substance abuse or dependence within prior 6 months
• Positive urine drug screen for illicit substances
• Use of other psychedelics or ketamine within prior 12 months
• Adverse prior reaction to a psychedelic agent
• Pregnant, trying to get pregnant, or nursing

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Center for Complementary and Integrative Health (NCCIH)

NIH

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Marc J. Weintraub, PhD

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UCLA Semel Institute

Los Angeles, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Shelby Grody

Role: CONTACT

UCLAPAT@mednet.ucla.edu

310-825-4354

Facility Contacts

Shelby Grody

Role: primary

UCLAPAT@mednet.ucla.edu

3108254354

Other Identifiers

R34AT013077

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-2134

Identifier Type: -

Identifier Source: org_study_id