Effects and Therapeutic Potential of Psilocybin in Alcohol Dependence

Inclusion Criteria: 1. Males and females age 25-65 with diagnosis of alcohol dependence, as ascertained using the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV version); 2. Concerned about their drinking, but not planning to pursue any other form of treatment at present (12-step meetings are not considered treatment); 3. Able to provide voluntary informed consent; 4. Having at least 2 heavy drinking days in the past 30 days; 5. Willing to commit to the goal of abstinence at least from the time of the first psilocybin administration session until the end of treatment. 6. At least 24 hours abstinence from alcohol at the time of the psilocybin administration sessions; 7. If female of childbearing potential, willing to use approved form of contraception from screening until after the psilocybin administration sessions; 8. Having a family member or friend who can pick them up and stay with them overnight after the psilocybin administration sessions; and 9. Able to provide adequate locator information. Exclusion Criteria: 1. Exclusionary medical conditions (e.g., seizure disorder, significantly impaired liver function, coronary artery disease, uncontrolled hypertension, history of cerebrovascular accident, severe obesity (BMI greater than or equal to 35); 2. Exclusionary psychiatric conditions (schizophrenia, schizoaffective disorder, bipolar disorder, current major depression, current post-traumatic stress disorder, current suicidality); 3. A family history of schizophrenia, schizoaffective disorder, bipolar disorder, or suicide (first or second degree relatives); 4. Lifetime history of hallucinogen use on more than 10 occasions, or any use in the past 30 days; 5. Cocaine, psychostimulant, or opioid dependence (past 12 months) or current (past 30 days) use; 6. A history of medically significant suicide attempt or violent crime; 7. Significant alcohol withdrawal (CIWA-Ar score greater than 7); 8. Exclusionary laboratory abnormalities (any liver function test (LFT) greater than 5 times normal, ECG evidence of ischemia, serious abnormalities of complete blood count or chemistries); 9. Active legal problems with the potential to result in incarceration; 10. Pregnancy or lactation; 11. The need to take excluded medication (e.g., antidepressants, antipsychotics, psychostimulants, pharmacologic treatments for addictions). 12. High risk of adverse emotional reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, serious current stressors, lack of meaningful social support).