Evaluation of Very Low Nicotine Content Cigarettes in Adolescent Smokers

描述（由申请人提供）：该K01奖有助于实现候选人的长期目标，即为科学基础做出贡献，为未来香烟中尼古丁含量的监管政策提供信息，特别是因为该政策影响青少年。本申请中概述的活动为候选人提供了青少年吸烟，人类行为药理学和先进统计方法方面的优秀培训；候选人建议将这一知识应用于一项创新研究计划，重点是评估青少年吸烟者中尼古丁含量极低的香烟。将香烟中的尼古丁含量降低到不会上瘾的水平——2009年通过的《家庭吸烟预防和烟草控制法案》（FSPTCA）使这一策略成为可能——可以显著降低美国的吸烟率（Benowitz & Henningfield, 1994）。该立法有可能影响一生中吸烟的模式，使香烟对年轻人的强化作用减弱，从而减少青少年“吸烟者”成为终身吸烟者的数量（Sofuoglu & LeSage, 2012）。然而，关于极低尼古丁含量（VLNC）香烟对青少年的影响知之甚少。减少香烟需求的最佳尼古丁剂量，对吸烟地形的影响，这些香烟的可接受性以及青少年对这些香烟相对风险的认知都是悬而未决的问题。虽然美国食品和药物管理局（fda）强制要求减少香烟中的尼古丁含量有可能大幅降低人口吸烟率，但如果这些吸烟者从事代偿性吸烟或认为VLNC香烟危害低，减少香烟中的尼古丁含量可能会对青少年产生意想不到的负面影响。因此，评估青少年吸烟者使用VLNC香烟的积极和消极后果对于评估该政策的可行性至关重要。我们建议通过两项研究来检验VLNC香烟的影响，一项在实验室完成，另一项在自然环境中完成。在研究1中，我们将比较尼古丁含量（正常尼古丁含量，0.83）、降低尼古丁含量[0.28,0.10]和VLNC[0.06]毫克含量)不同的香烟对青少年吸烟者戒断诱导的渴望和戒断、影响、风险感知、产品可接受性和对普通品牌香烟需求的影响（n=78）。在研究2中，我们将随机抽取每天吸烟的青少年（n = 90），接受VLNC香烟或正常尼古丁含量（NNC; 0.83 mg）研究香烟，为期三周。参与者将被指示只抽这些香烟。我们将对总卷烟使用情况进行每日评估（包括研究卷烟和不合规使用普通品牌卷烟；这些每日数据将密切监测代偿性吸烟的证据），渴望和戒断，每周评估呼吸CO水平，卷烟可接受性，VLNC和NNC卷烟的风险认知以及对普通品牌卷烟的需求，以及使用前后尼古丁和有毒物质暴露（可替宁和NNAL）的测量。总体而言，该项目将有助于确定VLNC香烟如何影响青少年的真实吸烟行为，并阐明这些产品可能影响这种变化的潜在机制。这些知识将有助于建立科学基础，为未来的政策决策提供信息，未来从这一研究方向产生的资助申请将确保候选人成功过渡到成为一名独立的研究人员。总的来说，K01奖项中概述的研究和培训活动对一个重要的领域做出了贡献

DESCRIPTION (provided by applicant): This K01 award facilitates the attainment of the Candidate's long-term goal of contributing to the science base that will inform future regulatory policy on nicotine content in cigarettes, particularly as this policy affects adolescents. The activities outlined in this application afford the Candidate excellent training in youth smoking, human behavioral pharmacology and advanced statistical methods; and the Candidate proposes applying this knowledge to an innovative research plan focused on evaluating very low nicotine content cigarettes in adolescent smokers. Reducing the nicotine content of cigarettes to a non-addictive level - a strategy made possible by the 2009 passage of the Family Smoking Prevention and Tobacco Control Act (FSPTCA) - could dramatically reduce smoking rates in the US (Benowitz & Henningfield, 1994). The legislation has the potential to impact the pattern of cigarette smoking over the lifetime, making cigarettes less reinforcing for young people, and thus decreasing the number of teen "chippers" who go on to be lifelong smokers (Sofuoglu & LeSage, 2012). However, little is known about the effects of very low nicotine content (VLNC) cigarettes in adolescents. The optimal dose of nicotine for reducing cigarette demand, effects on smoking topography, acceptability of these cigarettes and adolescents' perceptions of the relative risks of these cigarettes are all open questions. While an FDA-mandated reduction in the nicotine content of cigarettes has the potential to dramatically reduce smoking rates in the population, reducing the nicotine content of cigarettes could have unintended negative consequences in adolescents if these smokers engage in compensatory smoking or perceive VLNC cigarettes as being low in harm. Therefore, evaluating the positive and negative consequences of VLNC cigarette use among adolescent smokers is critical for evaluating the viability of this policy. We propose to examine the effects of VLNC cigarettes using two studies, one completed in the laboratory and one in the natural environment. In Study 1, we will compare the effects of cigarettes varying in nicotine content (normal nicotine content, 0.83], reduced nicotine content [0.28, 0.10] and VLNC [0.06] mg yield) on abstinence-induced craving and withdrawal, affect, perceptions of risk, product acceptability and demand for usual-brand cigarettes in adolescent smokers across four laboratory sessions (n=78). In Study 2 we will randomize adolescent daily smokers (n = 90) to either receive VLNC cigarettes or normal-nicotine content (NNC; 0.83 mg) study cigarettes for three weeks. Participants will be instructed to smoke only those cigarettes. We will conduct daily assessments of total cigarette use (both study cigarette and non-compliant use of usual brand cigarettes; these daily data will be monitored closely for evidence of compensatory smoking), craving, and withdrawal, weekly assessments of breath CO levels, cigarette acceptability, risk perceptions of VLNC and NNC cigarettes and demand for usual-brand cigarettes, and pre- vs. post-use measures of nicotine and toxicant exposure (cotinine and NNAL). Overall, the project will help determine how VLNC cigarettes may affect real-world smoking behavior in adolescents, and illuminate the potential mechanisms through which these products may effect such changes. Such knowledge will contribute to the science base that may inform future policy decisions, and the future grant applications that will be generated from this line of research will ensure that the Candidate experiences a successful transition to becoming an independent researcher. Overall, the research and training activities outlined in this K01 award contribute both to an important area of scientific inquiry, and to the development of a productive and independent research career for the Candidate.