Between versus Within-Subject Models of the Protective Effect of Substance-Free Reward on Alcohol, Nicotine, and Marijuana Use and Problems

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Abstract Alcohol and substance use disorders (AUDs and SUDs) are among the leading causes of preventable mortality and healthcare costs in the United States. Across both preclinical (nonhuman animal) and human models of addiction, substance-free reward has been reliably implicated as an influential mechanism of addiction prevention and treatment. Substance-free reward refers to typically pleasurable, non-drug stimuli and activities (e.g., dating, sports, entertainment). However, the mechanism by which increases in substance-free rewards suppress substance misuse is not well understood. It could reflect a substitution, whereby the time spent engaging in a pleasurable activity prevents simultaneous drug use, or it could reflect an overall environmental enrichment, which the animal literature has connected to decreased addictive potential of the drug itself. The current proposal seeks to clarify this mechanism through two complementary approaches. One is a 21-day (3 times per day) ecological momentary assessment (EMA) protocol measuring engagement in substance-free pleasurable activities and alcohol, tobacco, and marijuana-related reward, use, and consequences. The second is a multi-method lab-experimental protocol that will characterize substance-related versus substance-free reward both through self-report questionnaires and brain responses to reward cues as measured via electroencephalogram (EEG). If an individual exhibits a relative imbalance between neural responses to substances versus natural rewards, they are likely to be at specific risk for substance misuse. Additionally, brain responses to specific substance-free rewards should map onto the actual rate of engagement of these activities during the EMA period. The results of this study have the potential to influence the structure of treatments for SUDs by informing 1) whether substance-free activity engagement is protective in the aggregate (e.g., through environmental enrichment) or is protective in a temporal dynamic fashion (e.g., by replacing substance use with a substance-free pleasurable activity instead), and 2) if neural measures can be used to predict whether treatment factors, such as relative reward imbalances between pleasurable activity engagement and substance-related reward, are reflected in day-to- day decisions regarding substance use.