Yale Center for the Study of Tobacco Product Use and Addiction: Flavors, Nicotine and Other Constituents (YCSTP)

总体摘要：YCSTP 烟草使用和成瘾仍然是美国十大公共卫生问题之一19以保护公众 为了健康，迫切需要采取监管措施，减轻烟草产品的吸引力和滥用责任 (世卫组织--烟草控制框架公约，2012年)。《家庭吸烟预防和烟草控制法》禁止 在烟草卷烟中添加具有人工或天然香料特征的添加剂。然而，薄荷醇是免税的 其他烟草产品包括多种口味。对调味品的进一步监管取决于研究 解决我们对香料对烟草/尼古丁吸引力的影响的理解上的重大差距 以及烟草使用的启动、发展和维持18。为了解决这一知识差距，YCSTP 使用多学科方法在FDA优先领域、行为方面生成基本的TRS证据 和瘾君子。为此，我们将研究不同口味(甜味和凉味)的作用。 包括甜味剂和新的凉爽味道，在开始、持续使用和对尼古丁/烟草上瘾时，以及 它们与减少危害的相关性。我们将建立在耶鲁TCORS-1产生的方法和结果的基础上，以及 将动物模型中的生物和行为测试与 人类将为调节烟草产品中的香料和尼古丁提供坚实的科学基础。 项目1(乔特/阿迪)将使用新的和已建立的临床前范例来检查是否 对香料和甜味剂的预适应会影响尼古丁使用行为和成瘾的出现，并且 新型冷却剂的影响，最终可能取代烟草产品中的薄荷醇。项目2 (Krishnan-Sarin/Green)将研究甜味和凉味对启动行为的影响 人类青年，在烟草启动谱上处于相对较早的阶段，并容易受到未来使用的影响。这 该项目还将研究甜味和凉味是否对改变尼古丁奖赏具有不同的重要性，以及 促进更年轻和更年长可燃烟草使用者的转换行为。项目3(索福格鲁)将 确定可燃烟草使用者释放尼古丁所需的最佳投放率 在产生最小积极影响的同时退出，以及在以下情况下是否改变了这种递交率的影响 可燃烟草使用者从使用薄荷醇产品转向使用非薄荷醇产品。YCSTP的目标将是 得到1)行政核心的支持，该行政核心将促进和确保成功完成所有拟议和 YCSTP、其他TCORS、NIH和FDA-CTP内部和之间的新研究和支持协作，2)a)a 实验室核心，将提供烟草产品、蒸气以及生物标志物的关键分析 接触尼古丁和香料，以及3)通过职业提升核心，将促进 研究员和初级教员作为独立的TRS调查人员。YCSTP还将使用多学科核心 对重点关注FDA-CTP需求和目标的“快速反应项目”公告作出反应的专业知识 YCSTP的。

Overall Abstract: YCSTP Tobacco use and addiction remain among the top 10 public health problems in the USA19 To protect the public health, regulatory measures that lessen the appeal and abuse liability of tobacco products are critically needed (WHO-FCTC, 2012). The Family Smoking Prevention and Tobacco Control Act (FSPTCA) prohibits the addition of characterizing artificial or natural flavors to tobacco cigarettes. However, menthol is exempt and other tobacco products include a wide variety of flavors. Further regulations of flavors depend on research addressing the significant gap in our understanding of the influence of flavors on the appeal of tobacco/nicotine and the initiation, progression and maintenance of tobacco use18. To address this knowledge gap, the YCSTP uses a multidisciplinary approach to generate essential TRS evidence in the FDA priority domains, Behavior and Addiction. Toward this end, we will examine the role of different classes of flavors (sweet and cool) including sweeteners and novel cool flavors, on initiation, continued use and addiction to nicotine/tobacco, and their relevance to harm reduction. We will build on the methods and findings generated in Yale TCORS-1, and integrate biological and behavioral testing in animal models with behavioral and pharmacological testing in humans to generate a firm scientific foundation for regulation of flavors and nicotine in tobacco products. Project 1 (Jordt/Addy) will use novel and established pre-clinical paradigms to paradigms to examine if preconditioning to flavors and sweeteners influences emergence of nicotine use behaviors and addiction, and the influence of novel cooling agents that may ultimately replace menthol in tobacco products. Project 2 (Krishnan-Sarin/Green) will examine the influence of sweet and cool flavors on initiation behaviors among human youth who are relatively early on the tobacco initiation spectrum and are susceptible to future use. This project will also examine if sweet and cool flavors are differentially important for altering nicotine reward, and facilitating switching behaviors, in younger and older combustible tobacco users. Project 3 (Sofuoglu) will determine the optimal delivery rates that are needed by combustible tobacco users to relieve nicotine withdrawal while producing minimal positive effects, and whether the influence of this delivery rate is altered if combustible tobacco users switch from using mentholated to non-mentholated products. YCSTP goals will be supported by 1) an administrative core that will facilitate and ensure successful completion of all proposed and new research and support collaborations within and across YCSTP, other TCORS, NIH and FDA-CTP, 2) a laboratory core that will provide critical analyses of tobacco products, vapor as well as markers of biological exposure to nicotine and flavors, and 3) by a career enhancement core that will promote the development of fellows and junior faculty as independent TRS investigators. The YCSTP will also use multidisciplinary core expertise to respond to “Rapid Response Project” announcements focused on FDA-CTP needs and the goals of the YCSTP.