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 迫切需要减少烟草产品的吸引力和滥用倾向的健康监管措施 （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》（FSPTCA）禁止吸烟。 向烟草香烟中添加特征性的人工或天然香料。然而，薄荷醇是豁免的， 其它烟草产品包括各种各样的香料。对口味的进一步规定取决于研究 解决了我们在理解香料对烟草/尼古丁吸引力的影响方面存在的重大差距 以及烟草使用的开始、发展和维持18。为了弥补这一知识差距，YCSTP 使用多学科方法生成FDA优先领域（行为）中的基本TRS证据 和成瘾。为此，我们将研究不同类别的口味（甜和凉）的作用 包括甜味剂和新型清凉香料，在开始、持续使用和尼古丁/烟草成瘾时， 与减少危害的相关性。我们将建立在耶鲁TCORS-1产生的方法和发现的基础上， 将动物模型中的生物学和行为学测试与 为烟草产品中的香料和尼古丁的监管奠定了坚实的科学基础。 项目1（Jordt/Addy）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处理影响尼古丁使用行为和成瘾的出现， 新型清凉剂的影响，可能最终取代烟草产品中的薄荷醇。计划2 （Krishnan-Sarin/绿色）将研究甜味和清凉味对 相对较早开始吸烟并容易在未来吸烟的人类青年。这 该项目还将研究甜味和凉味是否对改变尼古丁奖励具有不同的重要性， 促进年轻和老年可燃烟草使用者的转换行为。项目3（Sofuoglu）将 确定可燃烟草使用者释放尼古丁所需的最佳输送速率 撤回，同时产生最小的积极影响，以及是否改变这种交付率的影响，如果 可燃烟草使用者从使用含薄荷油的产品转向使用不含薄荷油的产品。YCSTP的目标将是 1）一个行政核心，将促进和确保圆满完成所有拟议的和 新的研究和支持YCSTP、其他TCORS、NIH和FDA-CTP内部和之间的合作，2）a 实验室核心，将提供烟草产品，蒸汽以及生物标志物的关键分析 暴露于尼古丁和香料，3）通过职业提升核心，这将促进 研究员和初级教师作为独立的TRS调查员。YCSTP还将使用多学科核心 响应"快速反应项目"公告的专业知识，重点关注FDA-CTP需求和目标 在YCSTP。

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.