Computer-Assisted Self-Administration of Ethanol

* GROUPS 1-5: All participants will be between the ages of 21 and 45 years, social drinkers in good health. Young females will have normal menstrual cycles and will be tested during the follicular phase of their cycle (within 10 days of offset of menses) and must have a negative urine pregnancy (hCG) test at the start of the study session. INCLUSION CRITERIA: 1. Male and female participants between 21-45 years of age. 2. Good health as determined by normal or non-clinically-significant findings on medical history, physical exam, ECG and lab tests. 3. Female participants will be tested during the follicular phase of their cycle (within 10 days of offset of menses) and must have a negative urine pregnancy (hCG) test at the start of each study session. For Group 5, due to the number of study visits, female subjects will be tested outside the menses phase of their cycle. 4. Group 5 will include 20 subjects who report at least 2 binge drinking episodes in the month prior to the study (a binge episode is defined as consuming at least 4 drinks for females and at least 5 drinks for males during the drinking episode) and 20 subjects who report no binge drinking episodes in the past month. EXCLUSION CRITERIA: 1. Current or prior history of serious medical illness, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders. 2. Positive hepatitis A, B antigen or C or HIV test at screening. 3. Current history of Axis-I psychiatric illness. 4. Current or lifetime diagnosis of alcohol or substance dependence. 5. Currently seeking treatment for alcohol use disorders. 6. History of significant withdrawal symptoms or presence of clinically significant withdrawal symptoms (Clinical Institute Withdrawal Assessment (CIWA) score \> 8) at screening. 7. Non-drinkers (alcohol-na(SqrRoot) ve individuals or current abstainers) or individuals with no experience drinking 5 or more drinks on one occasion in their lifetime. 8. Regular tobacco users will be excluded from the study in order to avoid nicotine withdrawal symptoms. Occasional use of tobacco products (up to 20 cigarettes/week) is acceptable. For Groups 3, 4 and 5, participants must be current non-smokers (past smokers who have quit for over 1 year can be included). 9. Positive result on urine drug screen or positive breathalyzer during screening visit or at the start of any study visit. 10. Pregnancy or intention to become pregnant for women. Female participants will undergo a urine beta-hCG test to ensure they are not pregnant. 11. Use of prescription or OTC medications known to interact with alcohol within 2 weeks of the study. These include, but may not be limited to: isosorbide, nitroglycerine, benzodiazepines, warfarin, anti-depressants such as amitriptyline, clomipramine and nefazodone, anti-diabetes medications such as glyburide, metformin and tolbutamide, H2-antagonists for heartburn such as cimetidine and ranitidine, muscle relaxants, anti-epileptics including phenytoin and phenobarbital codeine, and narcotics including propoxyphene, oxycodone and hydrocodone. Drugs known to inhibit or induce enzymes that metabolize alcohol should not be used for 4 weeks prior to the study. These include chlorzoxazone, isoniazid, metronidazole and disulfiram. Cough-and-cold preparations which contain anti-histamines, pain medicines and anti-inflammatories such as aspirin, ibuprofen, acetaminophen, celecoxib and naproxen, should be withheld for at least 72 hours prior to each study session. 12. Current or prior history of alcohol-induced flushing reactions. 13. Female participants who have abnormal menstrual cycles in the absence of irregularities caused by hormonal contraception, as defined by irregularities in menstrual cycle length (cycles of \>36 days or \< 8 cycles per year), clinically significant menstrual periods that are heavier or lighter than usual, and/or accompanied by significant pain, cramping or nausea and vomiting that requires intervention. GROUP 6 Group 6 will include heavy drinkers between the ages of 21 and 60 years, in good health. Unfortunately, heavy drinking does not have a universally agreed upon definition and the criteria used to define heavy drinking vary from study to study. There is evidence that incorporating both amount of alcohol consumed per occasion and amount of alcohol consumed per week is relevant to account for risk related to pattern of drinking and total consumption. Therefore in our study we will select heavy drinkers using a definition that takes into account both pattern of drinking and total consumption. For pattern of drinking, we will require our subjects to have on average at least one binge drinking day per week, using the NIAAA definition of 5 or more drinks for men and 4 or more drinks for women (NIAAA website). For total consumption, we will use an average of 8 or more drinks per week for women and 15 or more drinks per week for men as this level of drinking has been shown to confer increased risk of mortality. INCLUSION CRITERIA: 1. Male and female participants between 21-60 years of age. 2. Male participants must have consumed an average of 15 or more standard drinks per week and females must have consumed an average of 8 or more standard drinks per week during the past 90 days. Average number of drinks per week will be calculated based on total number of drinks as measured by the timeline followback (TLFB) (e.g., for 90 days worth of data, total drinks divided by 90 and then multiplied by 7 will be the average number of drinks per week). 3. Participants must have on average at least 1 binge drinking day per week during the last 90 days, defined as a day in which 4 or more standard drinks were consumed for females and 5 or more standard drinks were consumed for males. Average number of binge drinking days will be calculated based on total number of binge drinking days from the TLFB (e.g. for 90 days worth of data, participants with a total of 13 or more binge drinking days will be eligible). 4. Participants must be able and willing to refrain from consuming alcohol 24 hours prior to each alcohol self-administration session. EXCLUSION CRITERIA: 1. Current or prior history of serious medical illness, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders. 2. Positive hepatitis A, B antigen, or C or HIV test at screening. 3. Abnormal findings on ECG, unless cleared for participation by cardiologist or Licensed Independent Practitioner (LIP). 4. Current history of major depressive disorder, bipolar disorder, psychotic disorder, obsessive compulsive disorder (OCD), post-traumatic stress disorder (PTSD), eating disorder, or any other Axis-I psychiatric disorders requiring intervention. 5. An aspartate transaminase (AST) or alanine transaminase (ALT) level more than 3 times the upper limit of normal. 6. Current (past 12 months) diagnosis of substance use disorder other than alcohol use disorder, unless in early remission (no criteria met for at least 3 months). 7. Positive result on urine drug screen or breathalyzer test during initial or update visit under the screening protocol (14-AA-0181) most proximal to enrollment. Positive urine drug screen during more than 1 study visit or breathalyzer reading during more than 1 self-administration study visit will result in participant withdrawal from the study. 8. Currently seeking treatment for alcohol use disorder or having undergone inpatient or outpatient detoxification or treatment for alcohol problems in the past 6 months. 9. History of significant withdrawal symptoms or presence of clinically significant withdrawal symptoms (Clinical Institute Withdrawal Assessment (CIWA) score \> 8) at screening. 10. Pregnancy, intention to become pregnant, or breastfeeding. Female participants will undergo a urine beta-hCG test to ensure that they are not pregnant. 11. Medication exclusion criteria: 1. . Daily or regular use of prescription or OTC medications known to interact with alcohol in the 2-week period prior to assessment. These include, but may not be limited to: isosorbide, nitroglycerine, benzodiazepines, warfarin, anti-depressants such as amitriptyline, clomipramine and nefazodone, anti-diabetes medications such as glyburide, metformin and tolbutamide, H2-antagonists for heartburn such as cimetidine and ranitidine, muscle relaxants, anti-epileptics including phenytoin and phenobarbital codeine, and narcotics including propoxyphene, oxycodone and hydrocodone. 2. Daily or regular use of drugs known to inhibit or induce enzymes that metabolize alcohol in the 4-week period prior to assessment. These include chlorzoxazone, isoniazid, metronidazole and disulfiram. Note that any discontinuation of medications will only be done at the recommendation of a physician. 12. Current or prior history of alcohol-induced flushing reactions.