Psilocybin-assisted CBT for Depression

NCT ID: NCT05227612

Last Updated: 2025-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-27
• Study Completion Date: 2025-09-12

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 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.

Conditions

Major Depressive Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Interventions

Psilocybin

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

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 Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

UCLA Semel Institute

Los Angeles, California, United States

Countries

United States

References

Weintraub MJ, Jeffrey JK, Grob CS, Ichinose MC, Bergman RL, Cooper ZD, Miklowitz DJ. Psilocybin-Assisted Cognitive Behavioral Therapy for Adults with Major Depressive Disorder: Rationale and Treatment Development. Psychedelic Med (New Rochelle). 2023 Dec 13;1(4):230-240. doi: 10.1089/psymed.2023.0018. eCollection 2023 Dec.

Reference Type: DERIVED

PMID: 40046861 (View on PubMed)

Other Identifiers

R34AT013077-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

21-002134

Identifier Type: -

Identifier Source: org_study_id