A Double-Blind Trial of Psilocybin-Assisted Treatment of Alcohol Dependence

Inclusion Criteria: 1. Males and females age 25-65 with SCID (DSM-IV) diagnosis of alcohol dependence who 2. Want to stop or decrease their drinking 3. Are not participating in any formal treatment for alcohol dependence (12-step meetings are not considered treatment) 4. Are able to provide voluntary informed consent 5. Have at least 4 heavy drinking days in the past 30 days 6. If female of childbearing potential, are willing to use approved form of contraception from screening until after the psilocybin administration sessions 7. Have a family member or friend who can pick them up and stay with them overnight after the psilocybin administration sessions 8. Are able to provide adequate locator information. Exclusion Criteria: 1. Medical conditions that would preclude safe participation in the trial (e.g., seizure disorder, significantly impaired liver function, coronary artery disease, heart failure, uncontrolled hypertension (above 165/95 mmHg at screening), history of cerebrovascular accident, asthma, hyperthyroidism, narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, symptomatic prostatic hypertrophy, or bladder-neck obstruction) 2. Exclusionary psychiatric conditions (schizophrenia, schizoaffective disorder, bipolar disorder, current major depressive episode, current post-traumatic stress disorder, current suicidality or history of medically serious suicide attempt) 3. Cognitive impairment (Folstein Mini Mental State Exam score \< 26) 4. A family history of schizophrenia or schizoaffective disorder (first or second degree relatives), or bipolar disorder type 1 (first degree relatives) 5. History of hallucinogen use disorder, or any use in the past 1 year, or \>25 lifetime uses; 6. Cocaine, psychostimulant, opioid, or cannabis dependence (past 12 months) 7. Current non-medical use of cocaine, psychostimulants, or opioids (past 30 days) 8. Significant alcohol withdrawal (CIWA-Ar score greater than 7. Patients presenting at screening in withdrawal may be referred for detoxification and reassessed within 30 days) 9. Serious ECG abnormalities (e.g., evidence of ischemia, myocardial infarction, QTc prolongation \[QTc \> .045 for men, QTc \> .047 for women\]) 10. Serious abnormalities of complete blood count or chemistries 11. Active legal problems with the potential to result in incarceration 12. Pregnancy or lactation 13. Need to take medication with significant potential to interact with study medications (e.g., antidepressants, antipsychotics, psychostimulants, treatments for addictions, other dopaminergic or serotonergic agents, lithium, anticonvulsants). 14. Allergy or hypersensitivity to psilocybin or diphenhydramine. 15. High risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support).