Nicotinic Receptor Genetic Variation and Alcohol Reward

Eligibility Criteria

• 1. Male and female participants between 21-60 years of age. \[assessment: identification provided to Clinical Center Admissions office\]
• 2. Smoking status:
• * Smokers will have a history of at least 1 year of daily smoking, defined as individuals who smoke more than 20 uses of nicotinic products/week on average, and a cotinine level, measured by the NarcoCheck PreDosage Nicotine Test \[PNT\] test, of \>= 2. \[assessment: Smoking history questionnaire, Additional medical history, PreDosage Nicotine test\]
• * Non-smokers with no history of smoking in the past year and less than 20 uses of nicotinic products lifetime.\[assessment: smoking history questionnaire, Additional medical history\]
• 3. Inclusion criteria for women: 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\[s\]. Justification: To minimize the risk of administering alcohol to pregnant women, given the known effects of alcohol exposure on fetuses. \[assessment: medical history\]
• 1. Current or prior history of major medical illness, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders. Justification: Many illnesses may alter the neuropsychological effects of alcohol as well as MRI measures. \[assessment: clinically significant findings on medical history and physical exam, ECG, laboratory tests\]
• 2. Positive hepatitis \[A, B antigen, or C\], or HIV test at screening. Justification: Hepatitis can alter liver function and alcohol pharmacokinetics. HIV infection can alter brain function. \[assessment: laboratory tests\]
• 3. Current \[past 12 months\] history of psychiatric disorders, including depressive disorder, bipolar disorder, or anxiety disorders. Justification: Concurrent psychopathology can alter brain function and alcohol response. \[assessment: SCID interview\]
• 4. Lifetime history of psychotic disorders, obsessive compulsive disorder \[OCD\], post-traumatic stress disorder \[PTSD\], or eating disorder. Justification: These disorders can have long-term effects on brain function and alcohol response. \[assessment: SCID interview\]
• 5. Current or lifetime diagnosis of alcohol or substance use disorder. Past mild AUD or past mild SUD with no current symptoms for atleast 2 years will not be exclusionary. Justification: History of moderate to severe alcohol or substance use disorder will impact brain function and alcohol response. We do not anticipate past mild AUD or SUD in remission for 2+ years would have such impact on brain function and alcohol response. We will examine this in our exploratory analysis. We will also do a follow-up telephone/teleheath visit with these participants to assess any changes in alcohol or substance use or problems related to their participantion in the study \[assessment: SCID interview\]
• 6. Currently seeking treatment for alcohol use disorders. Justification: It would be unethical to administer alcohol to individuals seeking treatment for alcohol problems. Also, this study does not provide treatment for individuals with alcohol use disorder. \[assessment: medical history\]
• 7. History of significant withdrawal symptoms or presence of clinically significant withdrawal symptoms \[Clinical Institute Withdrawal Assessment \[CIWA\] score \> 8\] at screening. Justification: Withdrawal symptoms would be indicative of alcohol use disorder, which is already an exclusion criteria. Additionally, withdrawal symptoms would be a major safety concern for participants, and a major confound in the assessment of alcohol response and brain function. \[assessment: CIWA assessment\]
• 8. Non-drinkers \[alcohol-naive individuals or current abstainers\] or individuals with no experience drinking 5 or more drinks on one occasion in their lifetime. Justification: It would be unethical to administer alcohol to individuals that do not drink alcohol. \[assessment: Timeline Follow Back, Lifetime Drinking History, Additional History Form and medical history\]
• 9. Positive result on urine drug screen or positive breathalyzer during screening visit. Positive urine drug screen or breathalyzer reading during more than 1 study visit will result in participant withdrawal from the study. Justification: Current or recent exposure to alcohol or drugs of abuse could impact brain function and alcohol response. \[assessment: laboratory tests and breathalyzer test.
• 10. Current or prior history of alcohol-induced flushing reactions, including rapid reddening of the face, rapid heart rate and breathing, and nausea after 1 or 2 drinks. Justification: It would not be safe to administer alcohol to individuals with the highly aversive flushing response to alcohol. \[assessment: alcohol flushing questionnaire\]
• 11. Medication