Recruiting

Phase 1

Phase 2

Psilocybin & CBTRCT of Psilocybin-assisted CBT for Depression

Sponsor:

UCLA

Code:

NCT07281352

Conditions

Major Depressive Diorder

Eligibility Criteria

Sex: All

Age: 21 - 60

Healthy Volunteers: Not accepted

Interventions

Psilocybin (drug)

cognitive behavioral therapy

Minimal supportive therapy

Study Details

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 ID

NCT07281352

Start date

Jan 5, 2026

Status verified date

Dec, 2025

Completion date

Nov 30, 2027

Anticipated

Primary completion date

Nov 30, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 21 - 60

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

50 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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).

active comparator: 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).

Interventions

Psilocybin (drug)

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

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.

Minimal supportive therapy

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

Primary outcome measure

Client Satisfaction Questionnaire - 8 [ Time Frame: 4-month treatment period ]
Retention/Attrition [ Time Frame: 4-month treatment period ]
Hamilton Depression Rating Scale [ Time Frame: 7-month study period ]
Global Assessment of Functioning [ Time Frame: 7-month study period ]

Central Contacts and Locations

Central contacts

Shelby Grody

310-825-4354 UCLAPAT@mednet.ucla.edu

Locations

UCLA Semel Institute

Recruiting

Los Angeles, California, United States, 90095

Contacts

Shelby Grody

3108254354 UCLAPAT@mednet.ucla.edu

More Information

Sponsor

University of California, Los Angeles

Last update posted

Feb 12, 2026

Last verified

Dec, 2025

Keywords

psilocybin
cognitive behavioral therapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of California, Los Angeles on 2026-02-12.