Applying behavioral economics to screen medications for alcohol use disorder

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ABSTRACT Maladaptive decision-making processes are a hallmark of alcohol use disorder (AUD). A behavioral economic approach to AUD synthesizes concepts and methods from psychology and microeconomics to understand cognitive processes that contribute to overconsumption of alcohol. The excessive delay discounting of temporally distant rewards and increased alcohol demand is characteristic of individuals with AUD and provide support for dysfunctional decision-making processes. Thus, there is critical need to develop and identify treatments that can shift decision-making biases toward more adaptive choices. The multiple-choice procedure (MCP) was developed to efficiently investigate the relationship between drug preferences and alternative reinforcers. While the MCP has been used to examine the efficacy of medications for cocaine dependence, it has yet to be used to screen medications for AUD. The objective of this F32 NRSA application is to foster my development as an independent researcher with a focus on behavioral pharmacology for AUD and behavior economics applied to AUD. This application seeks to leverage an R21 human laboratory paradigm to screen AUD medications by adding an MCP. This addition will allow the applicant valuable training in conducting a behavioral pharmacology study, while using a robust behavioral economic approach to assess the clinical utility of medication effects on choice behaviors. A total of 64 men and women with current AUD and reporting intrinsic motivation to change their drinking, will be randomly assigned to receive naltrexone (50 mg QD), varenicline (1 mg BID), or matched placebo. Post-randomization, all participants will complete an alcohol cue- reactivity paradigm prior to the initial dose of study medication. After a week-long medication titration period, participants are asked to come into the laboratory to receive their second medication blister pack and to begin a 7-day practice quit attempt, during which they will have daily virtual (online and phone) visits where they will report on their alcohol. Additionally, a second cue-reactivity paradigm will be conducted 90 minutes following study drug administration on the final day of the practice quit attempt (Day 14). After the cue-reactivity paradigm, participants will complete the MCP, wherein participants choose between a standard alcohol drink immediately or a monetary reinforcer in one week, a delay discounting task, and a hypothetical purchase task to assess alcohol demand. Aim 1 tests the hypothesis that naltrexone and varenicline will decrease alcohol choice compared to placebo. Aim 2 tests the hypothesis that alcohol drinking during the practice quit attempt will predict alcohol choice and that medication effects will moderate this relationship. This represents an important step in: 1) evaluating the efficacy of AUD medications on alcohol choice over an alternative reinforcer and 2) my scientific development and maturity as an independent translational alcohol researcher with a focus on behavioral pharmacology and behavioral economics to study AUD.