Major Depressive DiorderPhase 1/2NCT07281352
RCT of Psilocybin-assisted CBT for Depression
A Phase 1/2 study testing Psilocybin (drug), cognitive behavioral therapy and Minimal supportive therapy in people with Major Depressive Diorder, run by University of California, Los Angeles at 1 site in United States.
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 Diorder
- What is being tested?
- Psilocybin (drug), cognitive behavioral therapy and Minimal supportive 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
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Jan 2026to 30 Nov 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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,
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- 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. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
UCLA Semel Institute
Los Angeles, California, 90095
Shelby Grody, 3108254354, UCLAPAT@mednet.ucla.edu
About this study
Official title: 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 is a randomized, two-arm, fixed dose trial that will test the feasibility, acceptability, and participant and therapist adherence to PA-CBT. Both treatment arms will receive two doses of psilocybin (10mg and then 25mg, separated by one month). In Phase II, participants will be randomized (1:1) to either a 12-session PA-CBT or a 6-session standard psilocybin-assisted therapy (PAT) condition (3 hours of preparation plus 3 hours of supportive therapy integration following the psilocybin experiences).
- Conditions
- Major Depressive Diorder
- Being tested
- Psilocybin (drug), cognitive behavioral therapy, Minimal supportive therapy
- Keywords
- psilocybin, cognitive behavioral therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin (drug)Drug
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.
Minimal supportive therapyBehavioural
Six total therapy sessions. Preparation for psilocybin in the first three sessions plus supportive, nondirective psychotherapy in the final three sessions.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: 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 (drug); Behavioral: cognitive behavioral therapy |
| Psilocybin + Minimal supportive therapy | Active comparator | Participants will receive 6 sessions of supportive, non-directive therapy along with two psilocybin-drug sessions -- the first following the third therapy session (10mg of psilocybin, taken orally) and the second following the fourth therapy session (25mg of psilocybin, taken orally). Receives: Drug: Psilocybin (drug); Behavioral: Minimal supportive therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Client Satisfaction Questionnaire - 8
Treatment acceptability as measured by the participant. Total scores range from 8 to 32, with the higher number indicating greater satisfaction.
Measured: 4-month treatment period
Retention/Attrition
Feasibility as measured by the number of participants retained in each treatment condition over the course of the study treatment
Measured: 4-month treatment period
Hamilton Depression Rating Scale
symptom severity scored from 0-53, with larger values indicating greater depressive severity
Measured: 7-month study period
Global Assessment of Functioning
psychosocial functioning scored from 0-100, with larger values indicating better functioning
Measured: 7-month study period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2025
- Study start5 Jan 2026
- Primary completion30 Nov 2027 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DiorderStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study involves randomization of 50 participants (1:1) to either PA-CBT or psilocybin-assisted therapy with minimal therapeutic support.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Principal investigator, Marc J. Weintraub, PhD, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07281352
- Sponsor's protocol ID
- 21-2134
- Other IDs
- R34AT013077
- Status last verified
- Dec 2025
- First submitted
- 8 Dec 2025
- Last updated
- 12 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 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
- NCT07281352
- Acronym / sponsor ID
- 21-2134
- Conditions
- Major Depressive Diorder
- Keywords
- psilocybin, cognitive behavioral therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 5 Jan 2026 (actual)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 30 Nov 2027 (estimated)
- First posted
- 15 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 is a randomized, two-arm, fixed dose trial that will test the feasibility, acceptability, and participant and therapist adherence to PA-CBT. Both treatment arms will receive two doses of psilocybin (10mg and then 25mg, separated by one month). In Phase II, participants will be randomized (1:1) to either a 12-session PA-CBT or a 6-session standard psilocybin-assisted therapy (PAT) condition (3 hours of preparation plus 3 hours of supportive therapy integration following the psilocybin experiences).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- The study involves randomization of 50 participants (1:1) to either PA-CBT or psilocybin-assisted therapy with minimal therapeutic support.
| Arm | Type | Receives |
|---|---|---|
| Experimental: Psilocybin + CBT | Experimental | Drug: Psilocybin (drug), 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). |
| Psilocybin + Minimal supportive therapy | Active comparator | Drug: Psilocybin (drug), Behavioral: Minimal supportive therapyParticipants will receive 6 sessions of supportive, non-directive therapy along with two psilocybin-drug sessions -- the first following the third therapy session (10mg of psilocybin, taken orally) and the second following the fourth therapy 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 |
|---|---|---|
| Psilocybin (drug)Participants will receive two doses of psilocybin (10mg, 25mg). | Drug | Experimental: Psilocybin + CBT, Psilocybin + Minimal supportive therapy |
| 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 | Experimental: Psilocybin + CBT |
| Minimal supportive therapySix total therapy sessions. Preparation for psilocybin in the first three sessions plus supportive, nondirective psychotherapy in the final three sessions. | Behavioural | Psilocybin + Minimal supportive therapy |
Primary outcome
Client Satisfaction Questionnaire - 8
Time frame: 4-month treatment period
Treatment acceptability as measured by the participant. Total scores range from 8 to 32, with the higher number indicating greater satisfaction.
Retention/Attrition
Time frame: 4-month treatment period
Feasibility as measured by the number of participants retained in each treatment condition over the course of the study treatment
Hamilton Depression Rating Scale
Time frame: 7-month study period
symptom severity scored from 0-53, with larger values indicating greater depressive severity
Global Assessment of Functioning
Time frame: 7-month study period
psychosocial functioning scored from 0-100, with larger values indicating better functioning
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2026.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Psilocybin (drug), cognitive behavioral therapy and Minimal supportive therapy in people with Major Depressive Diorder, 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: looking for participants now, as of the sponsor's last update on 12 Feb 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shelby Grody (310-825-4354, UCLAPAT@mednet.ucla.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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?
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 12 Feb 2026.