Title: Effect of Opioid Receptor Modulation on Alcohol Self-Administration and Neural Response to Alcohol Cues in Heavy Drinkers: Role of OPRM1 Gene Variation

Inclusion Criteria

• •ELIGIBILITY CRITERIA:
• •* Use of adequate method of birth control during the study, if female is sexually active and is not surgically sterilized. Adequate methods of contraception include: use of oral contraceptives; use of barrier method of contraceptive; use of an approved IUD or other long-acting reversible contraceptive (LARC); have a male sexual partner who is surgically sterilized; or have exclusively female sexual partner(s) \[assessment: medical history\].
• •EXCLUSION:
• •Current or prior history of major medical illness, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders \[assessment: clinically significant findings on medical history and physical exam, ECG, laboratory tests\].
• •Participation in any other pharmacological intervention study within 4 months prior to the start of this study \[assessment: medical history\].
• •Positive hepatitis A, B Antigen, or C, or HIV test \[assessment: laboratory test\].
• •An aspartate transaminase (AST) / alanine transaminase (ALT) ratio 3 times greater than the normal limit \[assessment: laboratory test\].
• •Diagnosis of Axis-I anxiety disorders or major depressive disorders in the past 12 months \[assessment: SCID interview\].
• •Lifetime diagnosis of Axis-I bipolar disorders or psychotic disorders \[assessment: SCID interview\].
• •Suicidal ideation in the past 6 months or suicidal behavior in the past 12 months \[assessment: Columbia Suicide Severity Rating Scale\].
• •Current diagnosis of substance use disorder (SUD), other than alcohol use disorder, mild cannabis use disorder (less than 4 criteria), or current SUD in remission. Current smoking or nicotine dependence is not exclusionary \[assessment: SCID-IV/SCID-5 interview, FTND\].
• •Positive result on urine drug screen or breathalyzer test during screening. Positive urine drug screen or breathalyzer reading during more than 1 study visit will result in participant withdrawal from the study \[assessment: laboratory tests and breathalyzer test performed at screening or update visit under 14-AA-0181 most proximal to enrollment\].
• •Currently (i.e., at the time of screening) seeking treatment for alcohol problems or have undergone inpatient or outpatient detoxification or treatment for alcohol problems in the past 6 months. \[assessment: medical history and physical exam\].
• •Lactose intolerance or rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption \[assessment: medical history and physical exam\].
• •Alcohol use:
• •* Current or prior history of alcohol-induced flushing reaction, including rapid reddening of the face, rapid heart rate and breathing, and nausea after 1 or 2 drinks \[assessment: medical history and physical exam, alcohol flushing questionnaire\].
• •* History of delirium tremens, hallucinations or seizures related to alcohol withdrawal \[assessment: medical history, CIWA-Ar, SCID interview\].