Psilocybin plus cognitive behavioral therapy for depression
Psilocybin-Assisted Cognitive Behavioral Therapy for Depression
This trial will test whether two doses of psilocybin given alongside cognitive behavioral therapy help adults aged 21–60 with major depressive disorder.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 50 (estimated) |
| Ages | 21 Years to 60 Years |
| Sex | All |
| Sponsor | University of California, Los Angeles Academic / other |
| Locations | 1 site (Los Angeles, California) |
| Trial ID | NCT07281352 on ClinicalTrials.gov |
What this trial studies
This randomized, two-arm Phase 1/2 trial gives all participants two fixed doses of psilocybin (10 mg then 25 mg one month apart) and compares a 12-session psilocybin‑assisted CBT program to a shorter 6‑session psilocybin‑assisted supportive therapy condition. The study will measure feasibility, acceptability, and adherence for both participants and therapists while collecting clinical outcome data on depressive symptoms. Phase II participants are randomized 1:1 to the longer PA‑CBT protocol or the standard supportive psilocybin-assisted therapy (3 hours of preparation plus 3 hours of post‑session integration). The protocol includes required in-person dosing visits at UCLA with a support person to escort participants home after sessions.
Who should consider this trial
Good fit: Adults aged 21–60 with a current major depressive episode and active symptoms (HAM-D >16), able to swallow capsules, medically cleared, and with an identified support person to escort them home are ideal candidates.
Not a fit: People with a personal or first/second‑degree family history of psychosis or bipolar disorder, uncontrolled high blood pressure, or those outside the 21–60 age range are unlikely to be eligible and may not benefit from this intervention.
Why it matters
Potential benefit: If successful, this approach could reduce depressive symptoms more effectively or produce more durable improvements by combining psilocybin experiences with structured CBT integration.
How similar studies have performed: Previous small clinical studies of psilocybin for depression have shown promising rapid antidepressant effects, but pairing psilocybin specifically with a structured CBT protocol is relatively novel.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Los Angeles, California
- UCLA Semel Institute — Los Angeles, California, United States (Recruiting)
Study contacts
- Study coordinator: Shelby Grody
- Email: UCLAPAT@mednet.ucla.edu
- Phone: 310-825-4354
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.