Major Depressive DisorderPhase 1NCT05227612

Psilocybin-assisted CBT for Depression

A Phase 1 study testing Psilocybin and Cognitive behavioral therapy in people with Major Depressive Disorder, run by University of California, Los Angeles at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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… Read more about this study

Who is it for?: Ages 21 to 60 years
Conditions the study is for: Major Depressive Disorder
What is being tested?: Psilocybin and Cognitive behavioral therapy
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteUnited States
Study dates: 27 Jun 2023to 12 Sep 2025
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

• 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.

Who cannot join

• 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,

Show all 15Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

UCLA Semel Institute
Los Angeles, California, 90095

Other trials in United States

About this study

Official title: Psilocybin-assisted Cognitive Behavioral Therapy for Depression

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
Being tested: Psilocybin, Cognitive behavioral therapy
Keywords: psilocybin, cognitive behavioral therapy (CBT)
Medical subject headings: Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PsilocybinDrug
Participants will receive two doses of psilocybin (10mg, 25mg).
Cognitive behavioral therapyBehavioural
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.

Study groups in NCT05227612
Study group	Role	What they receive
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). Receives: Drug: Psilocybin; Behavioral: Cognitive behavioral therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 4-month treatment period
Study Feasibility (Number of Participants That Completed the 4-month Treatment)
Retention of participants in the trial
Measured: 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
Measured: 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
Measured: Baseline, Post-treatment (an average of 4 months), and 3-month follow-up (an average of 7-months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Jun 202312 Sep 2025

First posted7 Feb 2022
Study start27 Jun 2023
Primary completion12 Sep 2025
Study completion12 Sep 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
More trials run by University of California, Los AngelesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: This study involves an open trial of 12 participant (i.e., all participants receive psilocybin-assisted cognitive behavioral therapy; PA-CBT).
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05227612
Sponsor's protocol ID: 21-002134
Other IDs: R34AT013077-01
Status last verified: Dec 2025
First submitted: 26 Jan 2022
Last updated: 19 May 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

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.
PubMed 40046861

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders
Anxiety Disorders, Major Depressive Disorder
RecruitingPhase 1
Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder
Healthy Volunteer, Major Depressive Disorder
RecruitingObservational study
Characterization and Treatment of Adolescent Depression
Depression
Recruiting
Defining Neurobiological Links Between Substance Use and Mental Illness
Major Depressive Disorder, Substance Use Disorder
RecruitingPhase 2
Study of ALTO-300 in MDD
Major Depressive Disorder

All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Psilocybin-assisted Cognitive Behavioral Therapy for Depression
ClinicalTrials.gov ID: NCT05227612
Acronym / sponsor ID: 21-002134
Conditions: Major Depressive Disorder
Keywords: psilocybin, cognitive behavioral therapy (CBT)
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: University of California, Los AngelesUniversity, hospital or other
Collaborators: National Center for Complementary and Integrative Health (NCCIH)
Study start: 27 Jun 2023 (actual)
Primary completion: 12 Sep 2025 (actual)
Study completion: 12 Sep 2025 (actual)
First posted: 7 Feb 2022 (actual)
Results: Posted 19 May 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: This study involves an open trial of 12 participant (i.e., all participants receive psilocybin-assisted cognitive behavioral therapy; PA-CBT).

Arm	Type	Receives
Psilocybin + CBT	Experimental	Drug: Psilocybin, Behavioral: Cognitive behavioral therapyParticipants 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).

Who may qualify

Ages: 21 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

• Ages 21-60,

Key exclusion criteria (15 listed)

• A personal or family history (first or second-degree) of psychosis or bipolar disorder

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PsilocybinParticipants will receive two doses of psilocybin (10mg, 25mg).	Drug	Psilocybin + CBT
Cognitive behavioral therapyTwelve 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.	Behavioural	Psilocybin + CBT

Primary outcome

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

Results and safety

Results posted to the registry on 19 May 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Psilocybin-assisted Cognitive Behavioral Therapy (PACBT)	16	16

Primary outcome: Treatment Acceptability (Client Satisfaction Questionnaire-8)

Time frame: 4-month treatment period. Mean (Standard Deviation). Unit: scores on a scale

Measure	Psilocybin-assisted Cognitive Behavioral Therapy (PACBT) n = 16
Value	30.8 (2.2)

Primary outcome: Study Feasibility (Number of Participants That Completed the 4-month Treatment)

Time frame: 4-month treatment period. Count of participants. Unit: Participants

Measure	Psilocybin-assisted Cognitive Behavioral Therapy (PACBT) n = 16
Value	16

Primary outcome: Hamilton Depression Rating Scale (HAM-D)

Time frame: Baseline, Post-treatment (an average of 4 months), and 3-month follow-up (an average of 7-months). Mean (Standard Error). Unit: scores on a scale

Measure	Psilocybin-assisted Cognitive Behavioral Therapy (PACBT) n = 16
Baseline	20.2 (1.0)
Post-treatment	9.9 (2.1)
3-month follow-up	9.6 (2.0)

Primary outcome: Global Assessment of Functioning (GAF)

Time frame: Baseline, Post-treatment (an average of 4 months), and 3-month follow-up (an average of 7-months). Mean (Standard Error). Unit: scores on a scale

Measure	Psilocybin-assisted Cognitive Behavioral Therapy (PACBT) n = 16
Baseline	56.1 (3.0)
Post-treatment	67.6 (3.0)
3-month follow-up	65.9 (2.7)

Adverse events

Time frame: From enrollment until end of follow-up (i.e., 7 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Psilocybin-assisted Cognitive Behavioral Therapy (PACBT)	0 of 16 (0%)	15 of 16 (93.8%)	0 of 16

Limitations and caveats (from the sponsor): There was no comparator to the PA-CBT condition. Additionally, the sample size was modest and follow-up was brief, limiting our ability to ascertain mechanisms of treatment effects. The study design would have been strengthened by measuring psilocybin mood states just prior to each psilocybin dose to better account for the psilocybin-specific antidepressant effects, since participants rated their pre-psilocybin mood states at the study's baseline assessment.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40046861Weintraub 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.

Related trials for Major Depressive Disorder

RecruitingPhase 2
Study of Neuro-Cognitive Correlates of Pediatric Anxiety Disorders
Anxiety Disorders, Major Depressive Disorder
RecruitingPhase 1
Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder
Healthy Volunteer, Major Depressive Disorder
RecruitingObservational study
Characterization and Treatment of Adolescent Depression
Depression
Recruiting
Defining Neurobiological Links Between Substance Use and Mental Illness
Major Depressive Disorder, Substance Use Disorder
RecruitingPhase 2
Study of ALTO-300 in MDD
Major Depressive Disorder

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Psilocybin and Cognitive behavioral therapy in people with Major Depressive Disorder, run by University of California, Los Angeles at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Acceptability (Client Satisfaction Questionnaire-8) (time frame: 4-month treatment period). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05227612, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026; AzTrials last refreshed its copy on 27 Oct 2026.