UCLA

moking and alcohol use problems contribute to over 250 million disability-adjusted lifeyears worldwide, with an estimated 1 in 5 adults engaging in recent heavy alcohol use and 1 in 7 reporting daily tobacco use. Effective pharmacotherapies for smoking and drinking are needed to test these effects among treatment-resistant populations who report significant cessation difficulties, particularly among those who co-use tobacco and alcohol. Converging evidence indicates that neuroimaging methods can be used to elucidate mechanisms of action and potentially, treatment outcomes, for addiction pharmacotherapies; these include varenicline and naltrexone, which are effective smoking cessation and drinking reduction aids, respectively. The proposed dissertation study therefore aims to: 1) examine pharmacotherapeutic effects of naltrexone and varenicline on neuroimaging paradigms of translational value (i.e. substance cueinduced neural activation), in an understudied population of East Asian heavy drinkers; 2) iii elucidate the relationship between response to alcohol cues in neuroimaging cue paradigms and responses in gold standard human laboratory paradigms (i.e. oral self-administration of alcohol); 3) explore whether smoking cue-induced neural responses predict smoking cessation outcomes in a comparison pharmacotherapy clinical trial. Such work is critical to understand the role of neuroimaging in medications and substance use research more broadly, and can support the prioritization of neuroimaging paradigms as indicated for treatment development pipelines.