AzTrials
AzTrials

Major Depressive DisorderPhase 2PsiloMDDAUDNCT04620759

Psilocybin Treatment of Major Depressive Disorder With Co-occurring Alcohol Use Disorder

A Phase 2 study testing Psilocybin in people with Major Depressive Disorder and Alcohol Use Disorder, run by Johns Hopkins University at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The purpose of this study is to determine whether psilocybin, a hallucinogenic drug, is effective in reducing depressive symptoms and amount of drinking in patients with co-occurring Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD). Read more about this study

Who is it for?
Ages 21 to 65 years
What is being tested?
Psilocybin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
90 participants
Where
1 siteUnited States
Study dates
14 Apr 2021to 30 Mar 2027
Phase
Phase 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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 21 to 65 years old
  • Fluent in English
  • Have given written informed consent
  • Have at least a high-school level of education or equivalent (e.g. GED).
  • Have a baseline GRID-HAMD score ≥ 16
  • Have a confirmed DSM-5 diagnosis of Major Depressive Disorder and currently experiencing a major depressive episode
Show all 21Show fewer
  • Have a confirmed DSM-5 diagnosis of Alcohol Use Disorder
  • Have undergone some form of therapy for MDD or AUD in the past, but are not interested in initiating standard pharmacotherapies for major depressive disorder or alcohol use disorder (e.g. selective serotonin reuptake inhibitor, disulfiram, naloxone, etc.)
  • Be judged by study team clinicians to be at low risk for suicidality
  • Average of at least 4 non-drinking day/month in the past 90 days, or a score of less than 4 on the PAWWS scale
  • Have at least 2 heavy drinking days per month in the past 90 days
  • Concurrent psychotherapy or pharmacotherapy with SSRIs, SNRIs, and/or bupropion is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study
  • Be medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
  • Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days
  • Agree to refrain from using any psychoactive drugs, including nicotine, within 24 hours of each drug administration. The exception is caffeine
  • Agree not to take any "as needed" medications on the mornings of drug sessions
  • Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration
  • Agree to use effective methods of contraception during the study (females)
  • Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals
  • Have limited lifetime use of hallucinogens (the following criteria are preferred: no use in the past 5 years; total hallucinogen use less than 10 times)
  • Proof of COVID-19 vaccination

Who cannot join

  • Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of contraception.
  • Blood liver tests assessed at screening that are outside of 3x the normal range
  • Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrilation), prolonged corrected QT (QTc) interval (i.e., QTc > 450 msec), artificial heart valve, or transient ischemic attack in the past year
  • Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) score > 9, or any other indication that the volunteer may experience medically complicated withdrawal from alcohol
  • Any history of seizures, including alcohol withdrawal seizures
  • Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
Show all 17Show fewer
  • Currently taking psychoactive prescription medication on a regular (e.g., daily) basis
  • Currently taking on a regular (e.g., daily) basis any antidepressant medications other than SSRIs, SNRIs, or bupropion, or any other medications that have a primary centrally-acting serotonergic effect, including mono-amine oxidase inhibitors (MAOIs). For individuals who have intermittent or "as-needed" use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
  • Currently taking more than 300mg bupropion daily
  • Currently taking medications for the treatment of depression or alcohol use disorder
  • Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder
  • Current or history within one year of meeting DSM-5 criteria for a moderate or severe substance use disorder (excluding caffeine, nicotine, and alcohol)
  • If a smoker or nicotine user, consuming the equivalent of more than 10 cigarettes per day.
  • Have a first or second-degree relative with schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition)
  • Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
  • History of a medically significant suicide attempt (e.g. an attempt characterized by strong intent and/or high lethality)
  • Has failed to respond to electroconvulsive therapy during the current major depressive episode

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Johns Hopkins Center for Psychedelic and Consciousness Research

    Baltimore, Maryland, 21224

Other trials in United States

About this study

The purpose of this study is to determine whether psilocybin, a hallucinogenic drug, is effective in reducing depressive symptoms and amount of drinking in patients with co-occurring Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD).

Read the detailed description

The objectives of this double-blind, placebo-controlled study are to test the hypotheses that a single high (25 mg) oral dose of psilocybin will lead to enduring reductions in depressive symptoms (as measured by the clinician-rated grid version of the Hamilton Depression Rating Scale, or GRID-HAMD) and amount of drinking (as measured using the Time Line Follow Back, or TLFB, procedure) compared to placebo in patients with co-occurring MDD and AUD. 90 male and female volunteers who are between the ages of 21 and 65 years old and who meet Diagnostic and Statistical Manual, Fifth Edition (DSM-5) criteria for MDD and AUD will be recruited from the community and complete all study procedures. Volunteers will be randomized to one of two study arms (psilocybin [N=45] or placebo [N=45]), and will complete a drug administration session paired with a brief Motivational Interviewing intervention for alcohol use. Volunteers will undergo assessments of depression and alcohol use before and after treatment. After primary endpoints are measured, all volunteers will receive a second, unblinded intervention with a single high dose of psilocybin (25 mg) to test a secondary hypothesis that two doses of psilocybin are more effective in treating MDD with co-occurring AUD than a single dose.

Being tested
Psilocybin, Placebo
Medical subject headings
Depressive Disorder, Major, Alcoholism

What participants receive

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

  • PsilocybinDrug

    Also called 4-phosphoryloxy-N,N-dimethyltryptamine

    The psilocybin used in this study is synthetically manufactured and formulated under current good manufacturing practices (cGMP). The active drug is encapsulated using a size 0 blue gelatin capsule and contains 25 mg of psilocybin.

  • PlaceboDrug

    The placebo used in this study is microcrystalline cellulose, an inert substance, encapsulated using a size 0 blue gelatin capsule.

Study groups in NCT04620759
Study groupRoleWhat they receive
Psilocybin TreatmentExperimentalParticipants will be administered 25mg of psilocybin in a clinical setting. Psilocybin is administered orally as a capsule and taken with water.
Receives: Drug: Psilocybin
PlaceboPlacebo comparatorParticipants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water.
Receives: Drug: Placebo

What is being measured

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

  1. Change from baseline in grid-version of the Hamilton Depression Rating Scale (GRID-HAMD) score

    The GRID-Hamilton Depression Rating Scale is a 17-item clinician-administered rating scale designed to assess severity of depressive symptoms. The score range for the GRID-HAMD is 0 to 52, with higher score indicating more severe depression.

    Measured: Baseline and 1 month after first experimental drug administration session

  2. Change from baseline in percentage of days abstinent as measured by the Time Line Follow Back (TLFB) assessment

    The TLFB is a widely used, standardized, calendar-based retrospective self-report assessment to quantify daily alcohol use. The investigators will examine the primary outcome of percentage of abstinent days in the past 90 days.

    Measured: Baseline and 3 months after first experimental drug administration session

  3. Change from baseline in percentage of days of heavy drinking as measured by the TLFB assessment

    The TLFB is a widely used, standardized, calendar-based retrospective self-report assessment to quantify daily alcohol use. The investigators will examine the primary outcome of percentage of drinking days in the past 90 days.

    Measured: Baseline and 3 months after first experimental drug administration session

  4. Change from baseline in gamma-glutamyl transferase (GGT)

    Change in GGT (IU/L) will be measured by peripheral blood tests. GGT is elevated in chronic drinkers. Elevated GGT due to drinking can begin to reduce after a week of abstinence, and can return to normal levels after roughly 4 weeks of abstinence.

    Measured: Baseline and 3 months after first experimental drug administration session

  5. Change from baseline in the percentage of carbohydrate deficient transferrin relative to total transferrin concentration (%CDT)

    Change in %CDT will be measured by peripheral blood tests. %CDT can become elevated after 1 to 2 weeks of heavy drinking, and can return to normal levels within 2 weeks of abstinence.

    Measured: Baseline and 3 months after first experimental drug administration session

  6. Change from baseline in the ratio of aspartate transaminase to alanine transaminase (AST/ALT)

    Change in AST/ALT ratio will be measured by peripheral blood tests. Elevated AST/ALT ratio has been associated with heavy drinking, and can return to normal levels after extended abstinence.

    Measured: Baseline and 3 months after first experimental drug administration session

Secondary outcomes (7)
  1. Change from baseline in Quick Inventory of Depressive Symptomatology - Self Rated (QIDS-SR) score

    The Quick Inventory of Depressive Symptomatology is a 16-item self-report questionnaire that measures the nine symptom domains of a depressive episode, with higher scores indicating greater depression severity. This questionnaire is rated on a scale of 0 to 3. These values represent varying answers for each item and can be found within the questionnaire.

    Measured: Baseline, 1 week, 1 month, and 3 month post-drug-session visits; 6 and 12 month follow-ups after the second experimental drug administration session.

  2. Change from baseline in State Trait Anxiety Index (STAI) score

    The STAI is a 40-item self-report measure that assessing anxiety on two different scales: State and Trait. State anxiety is scored on a 4-point scale (1 = Not at all; 2 = Somewhat; 3 = Moderately so; 4 = Very much so) and Trait anxiety is scored on the 4-point scale (1 = Almost never; 2 = Sometimes; 3 = Often; 4 = Almost always).

    Measured: Baseline, 1 week, 1 month, and 3 month post-drug-session visits; 6 and 12 month follow-ups after the second experimental drug administration session

  3. Change from baseline in percentage of days abstinent as measured by the TLFB assessment

    The TLFB is a widely used, standardized, calendar-based retrospective self-report assessment to quantify daily alcohol use. The investigators will examine the secondary outcome of percentage of abstinent days either within the last 30 days or the last 90 days, depending on study visit.

    Measured: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session, and at 6 and 12 months post second (unblinded) drug administration session

  4. Change from baseline in percentage of days of heavy drinking as measured by the TLFB assessment

    The TLFB is a widely used, standardized, calendar-based retrospective self-report assessment to quantify daily alcohol use. The investigators will examine the secondary outcome of percentage of drinking days either within the last 30 days or the last 90 days, depending on study visit.

    Measured: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session, and at 6 and 12 months post second (unblinded) drug administration session

  5. Change from baseline in GGT

    Change in GGT (IU/L) will be measured by peripheral blood tests. GGT is elevated in chronic drinkers. Elevated GGT due to drinking can begin to reduce after a week of abstinence, and can return to normal levels after roughly 4 weeks of abstinence.

    Measured: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session

  6. Change from baseline in %CDT

    Change in %CDT will be measured by peripheral blood tests. %CDT can become elevated after 1 to 2 weeks of heavy drinking, and can return to normal levels within 2 weeks of abstinence.

    Measured: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session

  7. Change from baseline in AST/ALT ratio

    Change in AST/ALT ratio will be measured by peripheral blood tests. Elevated AST/ALT ratio has been associated with heavy drinking, and can return to normal levels after extended abstinence.

    Measured: Baseline, 1 month post drug administration session, 3 months after the second (unblinded) drug administration session

Timeline

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

  1. First posted9 Nov 2020
  2. Study start14 Apr 2021
  3. Primary completion2 Mar 2026
  4. Study completion30 Mar 2027 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04620759
Sponsor's protocol ID
IRB00233684
Acronym
PsiloMDDAUD
Status last verified
Mar 2026
First submitted
3 Nov 2020
Last updated
13 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Psilocybin in people with Major Depressive Disorder and Alcohol Use Disorder, run by Johns Hopkins University 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 21 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 13 Mar 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. Some participants in this study may receive a placebo. 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 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?

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?

Change from baseline in grid-version of the Hamilton Depression Rating Scale (GRID-HAMD) score (time frame: Baseline and 1 month after first experimental drug administration session). The study lists 6 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 13 Mar 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in