Cue Incubation in Substance Use Disorders: Validation and Assessment of Mechanisms

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PROJECT SUMMARY Substance cue-reactivity is a central process underlying patterns of substance use. Because it is associated with relapse, it is an important target for interventions. Mechanistic research in rats indicates that reactivity to drug cues increases across the first month of abstinence, often referred to as cue incubation. Cue incubation has recently been demonstrated in several studies with humans, with cigarette, alcohol, methamphetamine, and cocaine use. Importantly, the degree of cue incubation varies between individuals, and has been related to risk of relapse in rat models. Thus, cue incubation may represent a critical process indexing vulnerabilities to relapse for humans in the early stages of drug use cessation. Further work is needed to assess this important source of variance in cue-reactivity with humans, and develop novel targets for intervention during this vulnerable period. Approach. In this study we will test for cue incubation in a sample of inpatients with cocaine use disorder in a residential drug-rehabilitation center. Primary measures of incubation will include self-report measures of craving, EEG-based late positive potential (LPP; indexing attentional engagement), and blood-based brain derived neurotrophic factor (BDNF; a well-validated measure of cue incubation in rats, indexing negative valence system engagement). We will include additional measures of candidate mechanisms underlying cue incubation based on the Research Domain Criteria (RDoC) framework, including control (executive function), arousal, and positive and negative valence systems (e.g. reward and loss processing, response inhibition and execution, and affective image processing). Goal. The proposed work will examine cue incubation in humans with cocaine use disorder. We will measure incubation at subjective, behavioral, neural, and biochemical levels, and include sufficient numbers of participants to examine predictors of incubation across individuals. These studies will provide a critical bridge between animal and human studies of incubation, and novel, comprehensive, information about candidate processes underlying cue incubation in humans – with the goal of advancing the utility of the cue incubation hypothesis in etiologic and intervention work with humans.