Nicotine Metabolism and the Development of Addiction in Adolescent Light Smokers

青少年轻度吸烟者的尼古丁代谢和成瘾的发展

• 批准号: 8267718
• 负责人: MARK L RUBINSTEIN
• 金额: $ 42.24万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8267718
• 关键词: 16 year old; Accounting; Adolescence; Adolescent; Adult; Affect; Behavioral; Cigarette; Conflict (Psychology); Confusion; Consumption; Cotinine; Data; Development; Dopamine; Gender; Genetic; Genetic Markers; Genetic Variation; Individual; Intake; Intervention; Light; Malignant Neoplasms; Measurement; Measures; Metabolic; Metabolism; Methods; Modeling; Nicotine; Nicotine Dependence; Outcome; Pathway interactions; Pharmacotherapy; Physiological; Population; Predisposition; Prevention; Prevention strategy; Process; Prospective Studies; Proxy; Questionnaires; Race; Research; Research Design; Research Personnel; Risk; Saliva; Salivary; Sampling; Signs and Symptoms; Smoke; Smoker; Smoking; Smoking Behavior; Syndrome; Teenagers; Time; Tobacco; Tobacco use; Toxin; Variant; Withdrawal; Withdrawal Symptom; addiction; adolescent smoking; age group; base; cigarette smoking; cohort; cytochrome P-450 CYP2A6 (human); design; early experience; experience; follow-up; hydroxycotinine; improved; insight; neurochemistry; nicotine replacement; prevent; prospective; reinforcer; research study; response; smoking cessation; social; treatment strategy

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.

项目概要 研究表明，存在某些遗传标记的成年吸烟者与吸烟速度减慢相关。 尼古丁代谢 吸烟较少且更有可能戒烟。虽然看起来很可能是这样 尼古丁代谢影响吸烟者对尼古丁的依赖程度，对发育的影响 尼古丁依赖的影响尚不清楚。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：确定是否 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 检查尼古丁代谢率与香烟消费量之间随时间的关系 青少年早期/实验性吸烟者的前瞻性队列（目标 1）。我们还将审查协会 青少年早期/实验中尼古丁代谢率与成瘾发展之间的关系 吸烟者（目标 2）。研究设计：使用前瞻性队列设计，我们将检查以下因素的影响： 尼古丁代谢率（通过 3'-羟基可替宁/可替宁比率测量）对发育的影响 青少年早期/实验性吸烟者（13-16 岁，吸 1-14 支香烟）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，并进行唾液调查 将获得样品用于测定尼古丁代谢率。所有科目将于 6 点查看 月间隔最多 36 个月。成瘾将通过增加唾液可替宁水平来衡量，反映 使用标准化量表增加摄入量以及尼古丁成瘾体征和症状的发展。 意义：拟议的研究对于理解一些青少年吸烟者的原因和方式至关重要 完成从实验到成瘾吸烟者的转变。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、不太可能戒烟并且考虑到吸烟相关毒素的累积效应，吸烟的风险增加 吸烟产生负面结果。因此，对青少年吸烟者进行早期干预是 对于阻止吸烟造成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到吸烟者的影响 尼古丁代谢的个体速率，在选择特定的尼古丁代谢速​​率时，代谢速率可能同样有用 青少年尼古丁替代品的形式。因此，研究尼古丁代谢的影响 青少年吸烟者可能提供新的重要见解，了解青少年可以从尼古丁中受益 替代品，哪些可能更有可能从非尼古丁药物疗法或非尼古丁药物疗法中受益 药物干预。

项目成果

Smoking-related cue-induced brain activation in adolescent light smokers.

• DOI: 10.1016/j.jadohealth.2010.09.016
• 发表时间: 2011-01
• 期刊: JOURNAL OF ADOLESCENT HEALTH
• 影响因子: 7.6
• 作者: Rubinstein, Mark L.;Luks, Tracy L.;Moscicki, Anna-Barbara;Dryden, Wendy;Rait, Michelle A.;Simpson, Gregory V.
• 通讯作者: Simpson, Gregory V.