Evaluation of Very Low Nicotine Content Cigarettes in Adolescent Smokers

描述（由申请人提供）：该 K01 奖项有助于候选人实现为科学基础做出贡献的长期目标，该科学基础将为未来有关卷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、人类行为药理学和高级统计方法方面的良好培训；候选人建议将这些知识应用到一项创新研究计划中，该计划的重点是评估青少年吸烟者的尼古丁含量极低的香烟。将香烟的尼古丁含量降低到不会成瘾的水平——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——可以显着降低美国的吸烟率（Benowitz & Henningfield，1994）。该立法有可能影响一生中的吸烟模式，降低香烟对年轻人的强化作用，从而减少终生吸烟的青少年“烟民”数量（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。减少香烟需求的尼古丁最佳剂量、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 规定减少香烟尼古丁含量有可能显着降低人群的吸烟率，但如果这些吸烟者进行补偿性吸烟或认为 VLNC 香烟危害较低，那么减少香烟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 卷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 卷烟的影响，一项在实验室完成，另一项在自然环境中完成。在研究 1 中，我们将在四个实验室会议 (n=78) 中比较不同尼古丁含量的香烟（正常尼古丁含量，0.83]、降低的尼古丁含量 [0.28, 0.10] 和 VLNC [0.06] 毫克产量）对青少年吸烟者戒烟引起的渴望和戒断、情感、风险认知、产品可接受性和对常用品牌香烟需求的影响。在研究 2 中，我们将每天吸烟的青少年 (n = 90) 随机分组，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这些香烟。我们将对卷烟总使用量（研究卷烟和常规品牌卷烟的不合规使用；这些日常数据将受到密切监测，以寻找补偿性吸烟的证据）、渴望和戒断进行每日评估，每周评估呼吸二氧化碳水平、卷烟可接受性、VLNC和NNC卷烟的风险认知以及对常规品牌卷烟的需求，以及尼古丁和有毒物质暴露（可替宁和NNAL）的使用前与使用后测量。总体而言，该项目将有助于确定 VLNC 卷烟如何影响现实世界中青少年的吸烟行为，并阐明这些产品可能影响此类变化的潜在机制。这些知识将有助于奠定科学基础，为未来的政策决策提供信息，而从这一研究领域产生的未来拨款申请将确保候选人成功过渡为独立研究人员。总体而言，K01 奖项中概述的研究和培训活动对以下一个重要领域做出了贡献： 科学探究，并为候选人发展富有成效的独立研究生涯。

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.