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: 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
• 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

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，具有某些遗传标志物的成年吸烟者与尼古丁代谢较慢有关的烟雾吸烟较少，更可能戒烟。尽管尼古丁代谢似乎可能会影响吸烟者的尼古丁依赖程度，但对尼古丁依赖性发展的影响尚不清楚。由于成瘾最常发生在青春期，因此在此期间专注于吸烟的前瞻性研究对于向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：确定尼古丁代谢的速率是否影响青少年对尼古丁成瘾的敏感性。具体目的：我们将在青少年的早期/实验吸烟者中，随着时间的流逝，尼古丁代谢和香烟消耗的速率之间的关联（AIM 1）。我们还将研究尼古丁代谢率与青少年早期/实验吸烟者成瘾的发展之间的关联（AIM 2）。研究设计：使用前瞻性队列设计，我们将研究尼古丁代谢率（通过3'-羟基霉素/可替宁比率测量的尼古丁代谢率）对青少年早期/实验性烟民（13-16岁的人每周吸烟1-14名香烟13-16岁）中尼古丁成瘾的发展。在基线时，将管理吸烟行为和成瘾问卷，并将获得唾液样本以确定尼古丁代谢率。然后，所有受试者将以6个月的间隔长达36个月。成瘾将通过增加唾液可替宁水平来衡量，以反映摄入量增加以及使用标准化尺度的尼古丁成瘾体征和症状的发展来衡量。意义：拟议的研究对于理解某些青少年吸烟者从实验到上瘾的吸烟者的过渡至关重要。尽管只有一小部分青少年吸烟，但我们知道那些继续吸烟的人更有可能在大量吸烟中吸烟，戒烟的可能性较小，并且考虑到与吸烟相关的毒素的累积作用，因此会增加吸烟会产生负面结果的风险。因此，在青春期吸烟者中进行介入对于制止吸烟的毁灭性影响至关重要。此外，正如对成年吸烟者的研究表明，对吸烟戒烟的药物治疗的反应可能受吸烟者的个体尼古丁代谢率的影响，在选择青少年的尼古丁替代品时，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，这些见解可能会从中受益于尼古丁替代品，并且可能更有可能从非尼科丁药物治疗或非药理干预措施中受益。公共卫生相关性：从这项研究中得出的数据将为我们提供有关某些青少年吸烟者从实验到上瘾吸烟者的过渡的基本信息。当我们更好地了解青少年尼古丁成瘾时，我们可以改善青少年吸烟者的预防和治疗策略，从而防止与烟草使用相关的大量可预防癌症。