Tobacco addiction is the leading cause of morbidity and mortality in the United States. Because tobacco use typically begins among adolescents and many teenagers try to quit, experience withdrawal and fail, a better understanding of tobacco withdrawal and effective interventions to treat tobacco dependence and withdrawal among young smokers are critically needed. In adult smoking cessation studies tobacco dependence and withdrawal include changes in affect and cognition. Change in negative affect was a significant mediator of the effects of bupropion, a non-nicotine pharmacological agent. This study will examine how tobacco dependence and withdrawal influence cognitive and affective states in adolescent smokers. It will also evaluate whether the effects of tobacco withdrawal in adolescent smokers are reduced by treatment with bupropion, which is also used in mood disorders and childhood ADHD, and is currently approved for adult smoking cessation treatment. This 10-week study consists of an unassisted (pretrial) acute tobacco withdrawal (AW) phase and a 7-week randomized double-blind placebo-controlled trial of bupropion (300 mg/day) for tobacco dependence. Neuropsychological examinations will be conducted at baseline, during acute withdrawal, and during treatment (including early withdrawal) with bupropion. We expect smoking cessation in approximately 25% of the active medication group and significant overall smoking reduction. We postulate that bupropion will also reduce the irritability, depressed mood and anxiety symptoms that typically occur during tobacco withdrawal. We expect to observe optimal cognitive performance, (i.e., attention, memory), and affective state during satiety, impairment during pre-treatment abstinence, and intermediate level cognitive performance in the abstinent active-treatment group. Because limited data are available on cognitive tasks in adolescent smokers, a non-smoking group will be included in order to establish the validity and appropriateness of our paradigm with a normative sample. The main potential risks of this study are linked to the medication, which was found to be safe in several adult trials. A potential benefit of this study is the improvement in health status due to cessation or reduction of tobacco exposure in adolescents. This study will also determine the effects of tobacco withdrawal on cognitive and affective states and how they can be addressed early in the addictive cycle.
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