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相关，速度较慢 尼古丁新陈代谢吸烟更少，戒烟的可能性更大。尽管看起来很有可能 尼古丁代谢影响吸烟者尼古丁依赖程度，对发育的影响 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， 关注这一时期吸烟的前瞻性研究对于我们提供有关吸烟的信息是必不可少的。 尼古丁代谢对成瘾进展的影响。前言：目的：确定患者是否存在不稳定性。 尼古丁代谢影响青少年对尼古丁成瘾的易感性。具体目标：我们将 研究尼古丁代谢率与吸烟之间的关系。 青少年早期/实验吸烟者的预期队列(目标1)。我们还将研究该协会 青少年早期/实验性尼古丁代谢率与成瘾发展的关系 吸烟者(目标2)。研究设计：使用前瞻性队列设计，我们将检查 尼古丁代谢率(用3‘-羟基可替宁/可替宁比率衡量) 青少年早期/实验性吸烟者(13-16岁，吸烟者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调查问卷以及唾液 将获得用于测定尼古丁代谢率的样本。所有受试者将在6点出场 间隔月份最长可达36个月。成瘾将通过增加唾液中的可替宁水平来衡量，反映 增加摄入量，并使用标准化的量表发展尼古丁成瘾迹象和症状。 意义：这项拟议的研究对于了解一些青少年吸烟者的原因和方式至关重要 从实验者转变为吸烟者上瘾。尽管只有一小部分青少年 吸烟，我们知道那些在成年后继续吸烟的人更有可能吸烟 由于吸烟相关毒素的累积影响，戒烟的可能性较小，因此患上吸烟的风险增加 因吸烟而产生不良后果。因此，对青少年吸烟者进行早期干预是 对于阻止吸烟的破坏性影响至关重要。此外，根据对成年吸烟者的研究， 提示对戒烟药物治疗的反应可能受吸烟者的 个体尼古丁代谢率，代谢率可能被证明在选择特定的 青少年尼古丁替代形式。因此，研究尼古丁代谢对健康的影响 青少年吸烟者可能会为哪些青少年可能受益于尼古丁提供新的重要见解 并且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受益 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.