Description (from grant):    

Although the concurrent abuse of alcohol and illicit drugs is the most common form of substance abuse in the United States today and is often accompanied by chronic cigarette smoking, the effects of polysubstance abuse on brain biology and function are not well understood. The primary goal of this proposal is to identify new neuroimaging and neuropsychological factors that relate to increased risk for relapse in individuals seeking treatment for polysubstance abuse. These factors will then be evaluated as to their ability to serve as practical clinical predictors of relapse after treatment, in an effort to focus limited treatment resources on those at greatest risk for relapse after substance abuse treatment. Our neuro-psychological focus is on traditional cognitive domains and measures of impulsive behavior and cognitive control. Our main neurobiological focus is on oxidative stress (OxS), hypothesized to underlie both PSUD and chronic smoking, and the neurobiological and systemic correlates of OxS. We further hypothesize that specific cognitive and regional MR abnormalities improve with abstinence and that longitudinal change measures during early remission predict subsequent relapse better than the corresponding cross-sectional measures. Additional MR measures will probe fronto-striatal neuronal injury, gliosis, glutamatergic and GABA-ergic effects, and perfusion deficits as they relate to cognition, self-regulation, and substance and tobacco use pre- and post-treatment. Studies will be conducted in treatment seekers with comorbid alcohol and cocaine use disorders (moderate to severe), with or without tobacco and mild cannabis use disorder. This hypotheses-driven proposal is aimed at identifying multifaceted determinants of continued substance misuse or abstinence as potential new targets for pharmacological and behavioral treatment of PSU. Showing neurobiological and functional improvements with abstinence will also help move public opinion to a mindset more helpfully described as `your brain in recovery'.