Evaluation of Very Low Nicotine Content Cigarettes in Adolescent Smokers

描述(由申请人提供)：该K01奖项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参考，特别是当这项政策影响青少年时。这份申请中概述的活动为候选人提供了在青年吸烟、人类行为药理学和先进统计方法方面的出色培训；候选人建议将这些知识应用于一项创新的研究计划，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)使这一战略成为可能--可以极大地降低美国的吸烟率(Benowitz&Henningfield，1994)。这项立法可能会影响一生中吸烟的模式，使香烟对年轻人的强度降低，从而减少青少年“烟瘾”的数量，这些青少年后来成为终身吸烟者(Sofuoglu&LeSage，2012)。然而，人们对极低尼古丁含量(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看法都是悬而未决的问题。虽然FDA规定的降低香烟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补偿性吸烟或认为VLNC香烟危害较低，降低香烟尼古丁含量可能会对青少年产生意想不到的负面后果。因此，评估在青少年吸烟者中使用VLNC香烟的积极和消极后果对于评估这项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，一项研究在实验室完成，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不同(正常尼古丁含量为0.83)、尼古丁含量降低[0.28，0.10]和VLNC[0.06]毫克产量的香烟对青少年吸烟者在戒烟诱导的渴望和戒断、情感、风险感知、产品可接受性和对普通品牌香烟的需求方面的影响(n=78)。在研究2中，我们将随机选择青少年日常吸烟者(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。参与者将被指示只吸那些香烟。我们将每天评估香烟的总使用量(研究香烟和不合规的常用品牌香烟的使用情况；这些每日数据将受到密切监测，以寻找补偿吸烟的证据)、渴望和戒烟，每周评估呼气一氧化碳水平、香烟的可接受性、对VLNC和NNC香烟的风险认知和对常用品牌香烟的需求，以及使用前和使用后尼古丁和有毒物质暴露的测量(可替宁和NNAL)。总体而言，该项目将有助于确定VLNC香烟可能如何影响青少年的现实世界吸烟行为，并阐明这些产品可能影响这种变化的潜在机制。这些知识将有助于为未来的政策决策提供科学基础，而这一研究领域将产生的未来拨款申请将确保候选人成功过渡到独立研究人员。总体而言，本K01奖项中概述的研究和培训活动有助于以下两个重要领域 科学探究，并为候选人发展富有成效和独立的研究生涯。

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.