In laboratory animals, repeated cycles of abstinence from and return to alcohol drinking can lead to changes in alcohol intake. In a study of the effect of abstinence on drinking in humans, the investigators found evidence that abstinence affects drinking differently in women compared to men. In the present study, the investigators propose to study how men and women respond to abstinence, and whether this information can be used to improve intervention and prevention strategies.

Women and men differ in how quickly they progress from social to problematic alcohol drinking. In laboratory animals, short-term abstinence increases alcohol consumption, with repeated deprivations leading to disordered drinking. In a preliminary study, the investigators found that men and women differed in how their motivation to drink alcohol changed after a short period of abstinence. The investigators hypothesize that this difference may affect their transition to alcohol use disorders. The objectives of this application are to characterize the human post abstinence response, and use identical alcohol exposures to study the mechanisms underlying identified sex differences. In addition, the investigators will complete a 2 year prospective study of natural drinking patterns to assess how self-reported abstinence intervals influence drinking trajectories. The long-term goal of this project is to inform alcohol use disorder treatment and to design and test novel interventions using the laboratory model of post-abstinence response. There is a critical unfilled need to understand sex differences in disease progression, and this lab-based assessment coupled to longitudinal follow-up provides the rigorous experimental design to begin to meet that need. This project will increase scientific knowledge by advancing the translation between preclinical and clinical models, eventually informing sex-specific intervention and prevention strategies for problematic drinking and establishing a model to test those interventions..

Inclusion Criteria:

• Moderate social drinkers
• Able to understand/complete questionnaires and procedures in English
• Body mass index (BMI) between 18.5 and 32 kg/m2
• Have venous access sufficient to allow blood sampling

Exclusion Criteria:

• Pregnant or breast-feeding women, or women who intend to become pregnant
• Do not attest to using accepted forms of birth control for the infusion phase of the study
• Current treatment for, or desire to be treated for, any substance use disorder or court ordered to not drink alcohol
• History of significant adverse reaction to alcohol
• Medical disorders or other conditions such as alcohol withdrawal seizures or delirium tremens that may influence study outcome or participant safety
• Medications (past 30 days) that could influence data or participant safety (e.g. antidepressants, antipsychotics, benzodiazepines, etc.) as determined by investigators
• DSM 5 Disorders (non AUD) or current/history of neurological disease of cerebral origin, or head injury with > 20 min loss of consciousness
• Positive breath alcohol reading on arrival at any study visit
• Actively suicidal (for example, any suicide attempts within the past year or any current suicidal intent, including a plan) or are at serious suicidal risk, by clinical judgment of the investigator
• Any condition for which the principal investigators determine it is unsafe or not prudent to enroll

The final raw dataset will be available to other researchers when we have collected all subjects and completed our own planned analyses. Prior to completion of our own planned analyses, we would be willing to consider releasing the dataset upon request. We will work with our IRB to establish a strategy for de-identifying the data while retaining the ability to ensure the quality of the stored data, and develop a data-sharing agreement.

After all subjects have been collected and the primary outcomes accepted for publication. The dataset will be available indefinitely,

On request to the PIs

The intervention is 2 weeks of monitored abstinence from alcohol compared to usual drinking. Thus, it is not possible to mask conditions for participants or investigators.