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

基本信息

批准号：
7695579
负责人：
MARK L RUBINSTEIN
金额：
$ 49.52万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
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/7695579
关键词：
16 year old Accounting Adolescence Adolescent Adult Affect Behavioral Cigarette Conflict (Psychology)Confusion Consumption Cotinine Data Development Dopamine Gender Genes 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 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 psychosocial public health relevance reinforcer research study response smoking cessation social treatment strategy

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Data derived from this study will provide us with essential information about why and how some adolescent smokers make the transition from experimentation to addicted smoker. As we better understand adolescent nicotine addiction, we can improve prevention and treatment strategies for adolescent smokers and thus prevent the multitude of preventable cancers associated with tobacco use.

描述（由申请人提供）：研究表明，存在某些与尼古丁代谢较慢相关的遗传标记的成年吸烟者吸烟较少，并且更有可能戒烟。尽管尼古丁代谢似乎可能影响吸烟者对尼古丁的依赖程度，但对尼古丁依赖发展的影响尚不清楚。由于成瘾最常发生在青春期，因此针对这一时期吸烟的前瞻性研究对于为我们提供有关尼古丁代谢对成瘾进展的影响的信息至关重要。目的：确定尼古丁代谢率是否影响青少年对尼古丁成瘾的易感性。具体目标：我们将在青少年早期/实验性吸烟者的前瞻性队列中研究随着时间的推移尼古丁代谢率与香烟消费之间的关联（目标 1）。我们还将研究青少年早期/实验性吸烟者的尼古丁代谢率与成瘾发展之间的关联（目标 2）。研究设计：采用前瞻性队列设计，我们将研究尼古丁代谢率（通过 3'-羟基可替宁/可替宁比率测量）对青少年早期/实验性吸烟者（13-16 岁）尼古丁成瘾发展的影响。每周吸 1-14 支烟的老年人）。在基线时，将进行吸烟行为和成瘾调查问卷，并获取唾液样本以确定尼古丁代谢率。所有受试者将每隔 6 个月至 36 个月接受一次检查。成瘾将通过增加唾液可替宁水平来衡量，该水平反映了摄入量的增加以及使用标准化量表出现的尼古丁成瘾体征和症状。意义：拟议的研究对于理解一些青少年吸烟者为何以及如何从尝试性吸烟者转变为成瘾吸烟者至关重要。尽管只有一小部分青少年吸烟，但我们知道，那些继续吸烟到成年的人更有可能大量吸烟，戒烟的可能性较小，并且考虑到吸烟相关毒素的累积效应，吸烟产生负面结果的风险增加。因此，对青少年吸烟者进行早期干预对于阻止吸烟造成的破坏性影响至关重要。此外，由于对成年吸烟者的研究表明，戒烟药物治疗的反应可能会受到吸烟者个体尼古丁代谢率的影响，因此在为青少年选择特定形式的尼古丁替代品时，代谢率可能同样有用。因此，研究尼古丁代谢对青少年吸烟者的影响可能会提供新的重要见解，了解哪些青少年可能从尼古丁替代品中受益，哪些青少年更有可能从非尼古丁药物治疗或非药物干预中受益。公共健康相关性：这项研究的数据将为我们提供有关一些青少年吸烟者为何以及如何从尝试性吸烟者转变为成瘾吸烟者的重要信息。随着我们更好地了解青少年尼古丁成瘾，我们可以改善青少年吸烟者的预防和治疗策略，从而预防多种与烟草使用相关的可预防癌症。