| Background: Despite significant public health efforts, cannabis and tobacco remain two of the most commonly used drugs by adolescents. Cannabis and tobacco use, co-use, and related disorders are common, and how the combined use of cannabis and tobacco impacts developing brain function, emotional states, and behaviors is poorly understood. Dysfunction in the neural processing of rewards is associated with cannabis and tobacco use disorders and developmentally-informed models are needed.;Objectives: To characterize neurophysiological (EEG), reinforcement sensitivity, negative affect, and chronic stress correlates of cannabis and tobacco use in adolescent daily cigarette smokers and typically developing controls. To examine the relationship between adolescent cannabis and tobacco use and two EEG measures of reward and punishment processing: (1) the feedback related negativity (FRN) and (2) event-related theta frequency band (4-8 Hz) oscillatory activity.;Methods: Adolescent daily cigarette smokers and age, gender, and grade-level matched typically developing controls were recruited from public schools and via local community advertising in the greater New Haven area. Towards objective 1 (reinforcement sensitivity, negative affect, and chronic stress correlates), all subjects completed a comprehensive battery of self-report measures querying sensitivity to rewards and punishments, impulsivity, negative affect, chronic stress, and substance use and addiction severity levels. Towards objective 2 (neural response to rewards and punishments) we used dense array EEG and a non-learning four choice guessing task with monetary reward, neutral (`breaking even'), and punishment conditions. Event-related potential (ERP) outcomes included FRN amplitude and latency. Event-related oscillation (ERO) outcomes included event-related spectral power (ERSP) and intertrial phase coherence (ITC) in the mediofrontal theta frequency band (4-8 Hz) from 200-400 msecs. Multivariate models and repeated measures analyses of variances (ANOVAs) were used to examine within and between group differences in neurophysiological indices of reward and punishment processing, psychological functioning, personality traits, and cannabis and tobacco use in adolescent smokers and typically developing controls.;Results: Sixty five participants (75% male; Mean Age = 17.7, SD = 1.40) including 36 smokers and 29 non-smoking typically developing controls met inclusionary criteria for the study and completed the experimental paradigm. With regard to psychological and personality trait correlates, adolescent daily cigarette smokers had high rates of both cannabis and tobacco use and reported increased negative life events, childhood trauma, and impulsivity, and decreased punishment sensitivity compared to controls. In examining psychological and personality measures as mediators of addiction severity levels in smokers, subjective sensitivity to rewards and impulsivity were independently predictive of cannabis use problem severity, while anxiety sensitivity was predictive of nicotine dependence. With regard to EEG outcomes, both FRN and event-related theta oscillations were associated with step-wise reward functions with increasing power from reward to neutral to punishment. No differences in FRN or reward-related theta activity were observed between non-deprived adolescent daily cigarette smokers and controls. Cannabis and tobacco produced both convergent and divergent effects on the EEG profile. Adolescent daily cannabis and tobacco users had significantly reduced theta oscillatory activity during the reward condition compared to adolescent daily tobacco non-daily cannabis users. Among adolescent daily cigarette smokers, FRN amplitude and theta oscillatory activity during reward feedback were positively and negatively associated with cannabis use problem severity and cannabis use respectively. Theta oscillations were also associated with nicotine dependence, nicotine withdrawal symptoms, and impulsivity in smokers and impulsivity and negative affect in typically developing adolescents.;Conclusions: Adolescent daily cigarette smokers have different psychological vulnerabilities, personality profiles, and neurophysiological patterns than typically developing controls, and these differences may contribute to the development and maintenance of cannabis and tobacco use disorders. Chronic stress, negative affect, reinforcement sensitivity, and impulsivity individually and interactively contribute to different cannabis and tobacco use patterns in youth, suggesting both general liability and substance-specific vulnerabilities. While adolescent smokers did not differ from typically developing adolescents in FRN or theta activity, the combined effects of cannabis and tobacco may have `normalized' smoker's EEG signals during the non-deprived state. Among adolescent daily smokers, cannabis use problem severity is associated with a neurophysiological and subjective reward hypersensitivity, and daily cannabis use is associated impaired cognitive control in the presence of rewards. Collectively, these findings support a dual process model for cannabis use in adolescent daily smokers producing both impaired `top-down' cognitive control over reward signaling and increased `bottom-up' reward signaling that may lead to poorer treatment response and higher risk for relapse during quit attempts. |
