Psilocybin Treatment of Major Depressive Disorder... — Clinical Trial Details

This randomised, quadruple-blind, placebo-controlled Phase II trial will randomise 90 adults (21–65 years) with DSM-5 major depressive disorder and alcohol use disorder to a single 25 mg oral dose of psilocybin or placebo, paired with a brief motivational interviewing session for alcohol use.

Primary outcomes are change in clinician-rated GRID-HAMD for depression and alcohol consumption via TLFB; after primary endpoints all participants will be offered a second unblinded 25 mg psilocybin dose to test additive effects of two doses.

Participants

Ages

21 – 65

Sexes

Male & Female

BMI

Psychosis History

Excluded

Inclusion Criteria

Inclusion Criteria:
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
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

Exclusion Criteria

Exclusion Criteria:
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 fibrillation), prolonged corrected QT (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

Company

Product

Legal

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

Detailed Description

Study Protocol

Preparation

Dosing

Locations

Related Publications

An Open-Label Study of Single-Dose Psilocybin for Borderline Personality Disorder With Co-Occurring Major Depressive Disorder

Integration

Therapeutic Protocol

Study Arms & Interventions

Psilocybin

Interventions

Placebo

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators