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: 8460577
• 负责人: MARK L RUBINSTEIN
• 金额: $ 40.11万
• 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 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8460577
• 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.

项目摘要 研究表明，具有某些遗传标记的成年吸烟者与较慢有关 尼古丁代谢吸烟较少，更有可能戒烟。虽然似乎很可能 尼古丁代谢会影响吸烟者中尼古丁依赖性的程度，这对发育的影响 尼古丁依赖性不太清楚。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有关的信息至关重要 尼古丁代谢对成瘾发展的影响。目的：确定率是否 尼古丁代谢会影响青少年对尼古丁成瘾的敏感性。具体目的：我们将 检查尼古丁代谢速​​率和随着时间的流逝之间的相关性 青少年早期/实验吸烟者的前瞻性队列（AIM 1）。我们还将检查协会 尼古丁代谢率与青少年早期/实验性成瘾的发展之间 吸烟者（目标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） 青少年早期/实验吸烟者（13-16岁吸烟1-14个香烟）中的尼古丁成瘾 每周）。在基线时，将对吸烟行为和成瘾问卷进行管理和唾液 将获得样品以确定尼古丁代谢率。然后将在6点看到所有主题 每月最多36个月。成瘾将通过增加反映的唾液可替宁水平来衡量 使用标准化量表增加了摄入量和尼古丁成瘾体征和症状的发展。 意义：拟议的研究对于理解某些青少年吸烟者的原因和如何 从实验到上瘾的吸烟者进行过渡。虽然只有一小部分青少年 抽烟，我们知道那些继续吸烟到成年的人更有可能吸烟 严重，戒烟的可能性较小，鉴于与吸烟相关的毒素的累积作用，有增加的风险 产生吸烟的负面结果。因此，在青春期吸烟者中介入的是 阻止吸烟的毁灭性影响至关重要。而且，随着成年吸烟者的研究 建议对吸烟药物疗法的反应可能受吸烟者的影响 尼古丁代谢的个体率，代谢率在选择特定时可能同样有用 青少年替代尼古丁的形式。因此，研究尼古丁代谢对 青少年吸烟者可能会提供新的重要见解，青少年可能会从中受益于尼古丁 替代品，这可能更有可能受益于非尼古丁药物疗法或非 - 药理学干预措施。