Nicotine Metabolism and the Development of Addiction in Adolescent Light Smokers

项目摘要 研究表明，成年吸烟者与某些遗传标记的存在有关， 尼古丁代谢减少吸烟，更有可能戒烟。尽管看起来 尼古丁代谢影响吸烟者尼古丁依赖的程度，对发展的影响 尼古丁依赖的原因还不太清楚。由于成瘾最常发生在青春期， 在这段时间内关注吸烟的前瞻性研究对于为我们提供有关吸烟的信息至关重要。 尼古丁代谢对成瘾进展的影响。目的：了解老年人的 尼古丁代谢影响青少年对尼古丁上瘾的敏感性。具体目标：我们将 研究尼古丁代谢率和香烟消费量之间的关系， 青少年早期/实验性吸烟者的前瞻性队列（目标1）。我们还将研究协会 尼古丁代谢率与青少年早期/实验成瘾发展之间的关系 吸烟者（目标2）。研究设计：采用前瞻性队列设计，我们将检查 尼古丁代谢率（通过3 '-羟基可替宁/可替宁比率测量）对发展的影响 青少年早期/实验性吸烟者（13-16岁，吸烟1-14支）的尼古丁成瘾 每周）。在基线时，将进行吸烟行为和成瘾问卷调查， 抽取样本以测定尼古丁代谢率。所有受试者将在6点 月间隔长达36个月。成瘾将通过增加唾液可替宁水平来测量， 使用标准化量表评估尼古丁摄入量增加和尼古丁成瘾体征和症状的发展。 意义：这项研究对于理解为什么以及如何让一些青少年吸烟至关重要。 从实验性吸烟者转变为吸烟成瘾者。虽然只有一小部分青少年 吸烟，我们知道那些继续吸烟到成年的人更有可能吸烟 严重，不太可能戒烟，并考虑到吸烟相关毒素的累积效应， 吸烟会产生不良后果。因此，在青少年吸烟者中进行早期干预， 这对阻止吸烟的破坏性影响至关重要。此外，对成年吸烟者的研究表明， 表明对戒烟药物治疗的反应可能受吸烟者的 尼古丁代谢率的个体，代谢率可以证明同样有用时，选择特定的 青少年尼古丁替代品因此，研究尼古丁代谢对 青少年吸烟者可能会提供新的和重要的见解，青少年可能受益于尼古丁 替代，可能更有可能从非尼古丁药物治疗或非尼古丁药物治疗中获益。 药物干预。

Project Summary Studies have shown that adult smokers with the presence of certain genetic markers associated with slower nicotine metabolism smoke fewer cigarettes and are more likely to quit. Although it seems likely that nicotine metabolism affects the degree of nicotine dependence in smokers, the impact on the development of nicotine dependence is less clear. Since addiction most frequently occurs during adolescence, prospective studies that focus on smoking during this time period are essential to give us information on the effects of nicotine metabolism on the progression to addiction. Objective: To ascertain whether the rate of nicotine metabolism affects adolescents' susceptibility to nicotine addiction. Specific aims: We will examine the association between the rate of nicotine metabolism and cigarette consumption over time in a prospective cohort of adolescent early/experimental smokers (Aim 1). We will also examine the association between the rate of nicotine metabolism and the development of addiction in adolescent early/experimental smokers (Aim 2). Study design: Using a prospective cohort design, we will examine the influence of the rate of nicotine metabolism (measured by the 3'-hydroxycotinine/cotinine ratio) on the development of nicotine addiction in adolescent early/experimental smokers (13-16 years-old who smoke 1-14 cigarettes per week). At baseline, smoking behavior and addiction questionnaires will be administered and saliva samples will be obtained for determination of nicotine metabolic rate. All subjects will then be seen at 6 month intervals up to 36 months. Addiction will be measured by increasing salivary cotinine levels reflecting increased intake and the development of nicotine addiction signs and symptoms using standardized scales. Significance: The proposed research is critical to understanding why and how some adolescent smokers make the transition from experimentation to addicted smoker. Although only a small percentage of teens smoke cigarettes, we know that those who continue smoking into adulthood are more likely to smoke heavily, less likely to quit and given the cumulative effect of smoking related toxins, are at increased risk for developing negative outcomes from smoking. Therefore, intervening early among adolescent smokers is essential to halt the devastating effects from smoking. Moreover, as studies of adult smokers have suggested that response to pharmacotherapy for smoking cessation may be influenced by a smoker's individual rate of nicotine metabolism, the metabolic rate may prove equally useful when choosing specific forms of nicotine replacement for adolescents. Therefore, research into the effect of nicotine metabolism on adolescent smokers may provide new and important insights into which teens may benefit from nicotine replacement and which may be more likely to benefit from non-nicotine pharmacotherapy or non- pharmacologic interventions.