The purpose of this study is to examine the effects of rapamycin (sirolimus) versus a placebo, an inactive substance, on responses to alcohol cues in individuals with alcohol use disorder. Rapamycin (sirolimus) is a FDA-approved antibiotic and immunosuppressive drug that is currently used to (a) prevent organ transplant recipients from rejecting their transplants (b) treat cardiovascular diseases, and (c) treat some forms of cancer. Rapamycin (sirolimus) is not FDA-approved to treat alcohol use disorder. The use of rapamycin (sirolimus) in this study is investigational, meaning that the study medication is not a proven treatment for alcohol use disorder. The study will examine the medication's use as a potential treatment for alcohol use disorder, as well as how safe and tolerable it is to take.

Inclusion Criteria:

• Must be treatment-seekers
• Meet criteria for alcohol use disorder
• Must be able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments
• Must use one of the following methods of birth control: oral contraceptives, barrier methods (diaphragm or condoms with spermicide or both), surgical sterilization, use of an intra-uterine contraceptive device, or complete abstinence from sexual intercourse
• Must live within a 50-mile radius of our research program and have reliable transportation,
• Must consent to remain abstinent from alcohol and all non-prescription drugs prior to medication administration and testing sessions
• Must consent to fast for a two-hour period prior to medication administration
• Must consent to random assignment to the rapamycin vs. placebo conditions.

Exclusion Criteria:

• Cannot be undergoing other alcohol cessation treatment
• Cannot be pregnant, nursing, or of childbearing potential and not using birth control
• Cannot have evidence of or a history of significant endocrine, cardiovascular, pulmonary, renal, or neurological disease
• Cannot have significant liver impairment
• Cannot have an existing infection or immune system disorder
• Cannot have a history of or current psychotic disorder, severe major depression, or bipolar affective disorder
• Cannot currently take anti-arrythmic agents, psychostimulants, or any other agents known to interfere with heart rate and skin conductance monitoring
• Cannot have known or suspected hypersensitivity to macrolide compounds (such as rapamycin/sirolimus)
• Cannot currently take medications that could adversely interact with the study medication, including but not limited to significant inhibitors of CYP2D6 or CYP3A4 (voriconazole, fluconazole, itraconazole, erythromycin, clarithromycin, diltiazem, verapamil, etc.), or significant inducers of CYP3A4, such as anticonvulsants (carbamazepine, phenobarbital, phenytoin, etc.) and antibiotics (rifabutin, rifapentine, etc.)
• Cannot have a history of thrombocytopenia, idiopathic thrombocytopenia purpura (ITP) or have a platelet count of less than 100,000 cells per mm3
• Cannot have any unhealed wounds
• Cannot have any planned surgeries within the next month, including surgical dental procedures
• Cannot have a history of complicated alcohol withdrawal symptoms (including, but not limited to, symptoms such as seizures, hallucinations, and high blood pressure)

Participants were assessed for adverse events between baseline and follow-up for a total of three weeks.