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

NCT04620759 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB00233684
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Major Depressive Disorder; Alcohol Use Disorder

Outcome Measures

Primary Outcomes (6)

• 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.

  Baseline and 1 month after first experimental drug administration session

• 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.

  Baseline and 3 months after first experimental drug administration session

• 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.

  Baseline and 3 months after first experimental drug administration session

• 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.

  Baseline and 3 months after first experimental drug administration session

• 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.

  Baseline and 3 months after first experimental drug administration session

• 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.

  Baseline and 3 months after first experimental drug administration session

Secondary Outcomes (7)

• Change from baseline in Quick Inventory of Depressive Symptomatology - Self Rated (QIDS-SR) score

  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.

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

  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

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

  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

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

  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

• Change from baseline in GGT

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

Study Arms (2)

Psilocybin Treatment

EXPERIMENTAL

Participants will be administered 25mg of psilocybin in a clinical setting. Psilocybin is administered orally as a capsule and taken with water.

Drug: Psilocybin

Placebo

PLACEBO COMPARATOR

Participants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water.

Drug: Placebo

Interventions

Psilocybin DRUG

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.

Also known as: 4-phosphoryloxy-N,N-dimethyltryptamine

Psilocybin Treatment

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Usona Institute: collaborator

Study Sites (1)

Johns Hopkins Center for Psychedelic and Consciousness Research

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Alcoholism

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Frederick S Barrett, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During the first phase of the study, participants will receive either placebo or treatment and all parties will be blinded. During the second phase of the study, all participants will receive treatment (open label).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 9, 2020
• Study Start: April 14, 2021
• Primary Completion: March 2, 2026
• Study Completion (Estimated): March 30, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (1)