Psilocybin-assisted CBT for Depression

NCT05227612 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 21-002134R34AT013077-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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

Keywords

psilocybin; cognitive behavioral therapy (CBT)

Outcome Measures

Primary Outcomes (4)

• Treatment acceptability

  participant and clinician feedback related to the joining of psilocybin with CBT

  4-month treatment period

• Treatment feasibility

  recruitment and retention of participants in the trial

  4-month treatment period

• Hamilton Depression Rating Scale

  symptom severity scored from 0-53, with larger values indicating greater depressive severity

  7-month study period

• Global Assessment of Functioning

  psychosocial functioning scored from 0-100, with larger values indicating better functioning

  7-month study period

Study Arms (1)

Psilocybin + CBT

EXPERIMENTAL

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).

Drug: Psilocybin; Behavioral: Cognitive behavioral therapy

Interventions

Psilocybin DRUG

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

Psilocybin + CBT

Cognitive behavioral therapy 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 + CBT

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

UCLA Semel Institute

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• 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.

  PMID: 40046861 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Psilocybin; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Clinical Professor

Model Details: This study involves an open trial of 12 participant (i.e., all participants receive psilocybin-assisted cognitive behavioral therapy; PA-CBT).

Study Record Dates

• First Submitted: January 26, 2022
• First Posted: February 7, 2022
• Study Start: June 27, 2023
• Primary Completion: September 12, 2025
• Study Completion: September 12, 2025
• Last Updated: December 12, 2025

Record last verified: 2025-12

Locations

US (1)