Psilocybin-assisted CBT for Depression

Psilocybin-assisted Cognitive Behavioral Therapy for Depression

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.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Psilocybin; Behavioral: Cognitive behavioral therapy

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Semel Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	Drug: Psilocybin; Participants will receive two doses of psilocybin (10mg, 25mg).; Behavioral: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Acceptability (Client Satisfaction Questionnaire-8)	Participant feedback related to the treatment on the Client Satisfaction Questionnaire-8. Scores can range from 8-32 with higher scores indicating greater satisfaction.	4-month treatment period
Study Feasibility (Number of Participants That Completed the 4-month Treatment)	Retention of participants in the trial	4-month treatment period
Hamilton Depression Rating Scale (HAM-D)	Symptom severity scored from 0-53, with larger values indicating greater depressive severity, as measured repeatedly at the baseline assessment	Baseline, Post-treatment (an average of 4 months), and 3-month follow-up (an average of 7-months)
Global Assessment of Functioning (GAF)	psychosocial functioning scored from 0-100, with larger values indicating better functioning	Baseline, Post-treatment (an average of 4 months), and 3-month follow-up (an average of 7-months)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2023
• Primary Completion (Actual): September 12, 2025
• Study Completion (Actual): September 12, 2025

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: psilocybin; cognitive behavioral therapy (CBT)
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin; Cognitive Behavioral Therapy
• Other Study ID Numbers: 21-002134; R34AT013077-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No