Phase 1 N=16 Treatment

Psilocybin-assisted CBT for Depression

Major Depressive Disorder

Bottom Line

View on ClinicalTrials.gov: NCT05227612 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

May 2026

Primary outcome: Primary: Treatment Acceptability (Client Satisfaction Questionnaire-8) — 30.8 scores on a scale

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: Psilocybin (Drug); Cognitive behavioral therapy (Behavioral)
Age: Adult · 21+ yrs
Sex: All
Sponsor: University of California, Los Angeles
Primary completion: Sep 2025

Outcome Measures

Outcome	Result	p-value
PRIMARY Treatment Acceptability (Client Satisfaction Questionnaire-8)	30.8	—
PRIMARY Study Feasibility (Number of Participants That Completed the 4-month Treatment)	16	—
PRIMARY Hamilton Depression Rating Scale (HAM-D)	20.2; 9.9; 9.6	—
PRIMARY Global Assessment of Functioning (GAF)	56.1; 67.6; 65.9	—

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 will involve an open trial of PA-CBT where participants will receive two doses of psilocybin (10mg and then 25mg, separated by one month) plus 12 sessions of cognitive behavioral therapy.

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05227612). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.