Sensitivity to Cannabis Effects and Cue Reactivity as Markers of a Developing Disorder in Adolescents

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PROJECT SUMMARY Cannabis use disorder (CUD) is a significant public health concern with origins in adolescence. Cannabis use escalates during the teenage years, and early cannabis use predicts the development of later problems. Leading etiological theories suggest that repeated cannabis use as the brain develops produces changes in reward systems. Over time, these instrumental brain changes alter cannabis effects and increase the incentive salience of cannabis cues, ultimately conferring risk for CUD. This longitudinal study pairs ecological momentary assessment (EMA) in the natural environment and a gold-standard human laboratory (HLAB) paradigm to monitor changes in subjective cannabis effects, cue reactivity, and CUD symptoms across the formative adolescent years. Leveraging smartphone (EMA) reports in natural settings allows for studying adolescents’ reactions to the typically higher potency THC products and varied formulations (e.g., oils, edibles) favored by teenagers. The use of an accelerated longitudinal design allows for charting development from ages 13 to 19 through multicohort assessments completed in a shorter timeframe. We aim to recruit 224 adolescents (ages 13 to 16 at study outset, n = 56 per age cohort) who endorse cannabis use in the past month. Adolescents will complete a baseline HLAB protocol with follow-ups at 1, 2, and 3 years. Each yearly assessment point will also include a 28-day measurement burst of EMA in daily life. Multiple domain latent growth curve modeling will: (Aim 1) characterize age-related changes in sensitivity to rewarding cannabis effects over adolescence (ages 13 to 19); (Aim 2) test prospective relations of CUD symptom progression with change in sensitivity to rewarding cannabis effects; and (Aim 3) test prospective relations of CUD progression with responses to cannabis cues in the natural environment and HLAB. The proposed longitudinal study extends the investigative team’s prior research showing cross-sectional associations of CUD severity with subjective cannabis effects and cue reactivity among adolescents. Our proposal is highly innovative, as well-studied etiological CUD constructs are assessed across adolescence in real-world and laboratory settings using well-operationalized, multidimensional assessments. Further, disaggregating individual differences in change from overall age trends through an accelerated longitudinal design is a sensitive approach that is distinctively innovative. Our proposal addresses a key priority identified by the NIDA Epidemiology Research Branch by efficiently combining the advantages of longitudinal research with behavioral and laboratory-based measures to inform understanding of CUD etiology (NOT-DA-19-066). This proposal will support efforts to prevent the progression of an incubating or emerging CUD by enhancing scientific understanding of the trajectory to more severe harms. Providing new empirical evidence of malleable processes that can serve as targets of preventative interventions has power to reduce the magnitude of societal ramifications of CUD.