In an effort to seek a more suitable method to measure alcohol clearance.

The study will involve administration of alcohol in a controlled laboratory setting to individuals who are scheduled for Roux-en-Y gastric bypass surgery, and then asking them to return for another laboratory session 3 months following their surgery. A small number will be asked to return again 9 months following their surgery.

The primary objective for this research is to collect pilot data on the effects of metabolic surgery (MS), also known as bariatric surgery, on the metabolism of alcohol. These data will be used as preliminary evidence in support of a subsequent application for funding, to be submitted to the National Institutes of Health.

A secondary objective for this research is to determine the extent to which MS changes reactivity to alcohol-related cues. Heightened reactivity (e.g., attention bias; craving) to alcohol-related cues is known to signify increased risk for heavy drinking and AUD. No research to date has examined whether the increased sensitivity to alcohol that occurs as a result of MS changes cue-reactivity responses, which in theory reflect an individual's history of learning to associate alcohol consumption with its subjective effects.

An exploratory objective is to compare metabolism of alcohol administered orally versus intravenously. IV infusion of alcohol bypasses so-called "first pass metabolism" of alcohol after absorption by the gastrointestinal tract. Thus, compared to oral ingestion, infusion can achieve the same blood alcohol concentration (BAC) with substantially less total alcohol dosage. Following the hypothesis, this should mean that, compared to oral ingestion, infusion will be associated with less production of liver fat, while also mimicking in pre-surgery patients what the investigators observe with oral ingestion following surgery. This comparison will permit better specification of when (during metabolism) and how alcohol is converted to liver fat, and will allow the investigators to separate effects of initial sensitivity to alcohol (a person's subjective response to the initial introduction of alcohol into the body) from effects associated with tolerance (i.e., the body's attempts to re-establish homeostasis after alcohol is introduced).

Inclusion Criteria:

• Obese, with body weight less than 450 lbs
• non-smoking female volunteers of any race
• age 30-55 years
• drink alcohol in moderation and meet all of the BSC's indications and criteria for RYGB surgery. NIH/NIAAA criteria specify an average of between 3 and 7 standard drinks per week as moderate alcohol drinking (for women). In addition, included participants must fall within the upper or lower tercile of scores on the ASQ for a bariatric population, as determined by the investigator's previous studies with this population.9,10,19

Exclusion Criteria:

• their AUDIT scores (16 or above) indicate the possibility of a current or prior alcohol use disorder.
• they report typically drinking less than once per month and consuming less than 3-4 drinks per occasion.
• they are taking prescribed psychoactive medications, other than selective serotonin reuptake inhibitors (SSRIs) for anxiety/depression.
• they are taking medications that might interfere with alcohol metabolism (e.g., anti-histamine h2 receptor antagonists [mainly, antacids used to treat GERD and gastro-intestinal ulcers], certain antibiotics such as erythromycin, or other drugs influencing hepatic cytochrome P450 2E1; see medicine.iupui.edu/clinpharm/ddis/table.aspx).
• their medical records indicate current anemia.
• their FTND scores indicate moderate or greater nicotine dependence (4 or above).
• they report they are trying to become pregnant, or produce a positive urine screen for pregnancy at the lab session.
• their body weight is > 450 lbs.
• they have participated in any other research study or medical procedure involving ionizing radiation exposure greater than a chest X-ray in the past 12 months.
• they live more than 60 miles from the CRC.