Psilocybin-assisted Therapy for Comorbid Major Depressive Disorder and Alcohol Use Disorder

Exclusion Criteria

• •Pregnant as assessed by a urine pregnancy test at Screening (V1) and Baseline (V2) or individual's that intend to become pregnant during the study or are breastfeeding;
• •Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension (over 160/100 mmHG), low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment.
• •Diagnosis of cirrhosis, AST or ALT elevations \> 3x upper limit of normal; significant abnormal liver function that would preclude administration of psilocybin based on the judgement of the QI (assessed notably by bilirubin, albumin, alkaline phosphatase, GGT, and INR functions)
• •Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; obsessive-compulsive disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview;
• •Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I or II disorder as determined by the family medical history form and discussions with the participant;
• •Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) score \> 9, or any other indication that the participant may experience medically complicated withdrawal from alcohol, such as a score of ≥4 in the Prediction of Alcohol Withdrawal Severity Scale.
• •Use benzodiazepines (with the exception of use of up to 2mg of lorazepam equivalent per day for insomnia and anxiety if it is not taken within 12 hours before the psilocybin dose (Week 2).
• •Have a DSM-5 diagnosis of substance use disorder (excluding alcohol, cannabis, tobacco and caffeine) within the preceding 6 months;
• •Presence of baseline prolonged QTc (more than 0.45 seconds for males and 0.47 seconds for females) or Torsade de Pointes as measured by the ECG or a history of long QTc syndrome or related risk factors;
• •Use of aldehyde dehydrogenase (ALDH) inhibitors and UDG modulators;
• •Use of hallucinogens in the past 5 years; or total hallucinogen use ≥10 times)
• •Current suicidality risk as indicated during the conduct of the Columbia Suicide Severity Rating Scale (C-SSRS) with concurrence after a study physician's evaluation if the response to C-SSRS questions 1 or 2 is "yes")
• •Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.
• •Participants that are responding to anti-alcohol or anti-craving medications