The Role of Nicotine and Non-Nicotine Alkaloids in E-Cigarette Use and Dependence

描述(由申请者提供)：电子烟和相关技术为减少吸烟造成的死亡和疾病提供了一个重要的潜在途径。然而，评估电子烟含量对产品使用和传统香烟同时吸烟的影响的受控调查相对较少。重要的是要确定电子烟的内容如何影响其使用，以及电子烟中没有传统香烟中存在的成分是否会阻碍可能已经依赖于传统香烟中这些成分的吸烟者接受。继续使用传统香烟和电子烟--电子烟目前占电子烟使用的相当大比例--将削弱从易燃香烟转向电子烟所带来的任何危害减少。香烟成瘾的关键是对尼古丁的依赖，但很可能是其他烟草成分导致了依赖。越来越多的证据表明，非尼古丁烟草生物碱或NNTAs(包括烟碱、烟碱、去甲烟碱和肌胺)与烟草依赖有关。这些生物碱已被证明在动物模型中增强尼古丁的增强作用，并影响人类吸烟者的渴望。电子烟含有不同数量的尼古丁和NNTAs，但当吸烟者试图从传统易燃香烟过渡到电子烟时，几乎没有关于电子烟尼古丁或NNTA含量在影响香烟和电子烟同时使用方面的作用的信息。此外，目前尚不清楚电子烟中尼古丁和NNTAs的存在是否会持续依赖，使人们难以戒除这些产品，并有可能增加青少年对这些产品的使用。拟议的研究将评估电子烟尼古丁和NNTA含量对吸烟者的影响，这些吸烟者将被随机分配到操纵电子烟尼古丁和NNTA含量的条件下。对电子烟和香烟的依赖和同时使用将通过一系列自我报告、生化和行为指数进行评估。这个项目的发现将直接应用于 FDA的监管决策。通过这样做，这些发现将有助于FDA的使命 有效地遏制烟草成瘾，使“与烟草有关的死亡和疾病成为美国过去的一部分”。

DESCRIPTION (provided by applicant): E-cigarettes and related technologies offer an important potential avenue for reducing the death and disease resulting from cigarette smoking. However, relatively few controlled investigations have been conducted to assess the influence of e-cigarette contents on product use and concurrent smoking of conventional cigarettes. It is important to determine how the contents of e-cigarettes influence their use and whether the absence of constituents in e-cigarettes that are present in conventional cigarettes provides a barrier to acceptability for smokers who may have become dependent on these constituents in conventional cigarettes. Continued use of conventional cigarettes along with e-cigarettes, which currently characterizes a substantial proportion of e- cigarette use, will attenuate any harm reduction associated with switching from combustible cigarettes to e- cigarettes. Cigarette addiction critically involves a dependence on nicotine, but it is likely that other tobacco constituents contribute to dependence. Mounting evidence implicates non-nicotine tobacco alkaloids, or NNTAs (including anabasine, anatabine, nornicotine and myosmine) in tobacco dependence. These alkaloids have been shown to augment the reinforcing effects of nicotine in animal models and to affect craving in human smokers. E-cigarettes contain variable quantities of nicotine and NNTAs, but there is virtually no information available concerning the role of e-cigarette nicotine or NNTA content in influencing the concurrent use of cigarettes and e-cigarettes, when smokers attempt to make a transition from conventional combustible cigarettes to e-cigarettes. Additionally, it is not known whether the presence of nicotine and NNTAs in e- cigarettes may sustain dependence, making it difficult to relinquish these products, as well as potentially increasing their use among adolescents. The proposed study will assess the effects of e-cigarette nicotine and NNTA content on cigarette smokers who will be randomized to conditions that manipulate the nicotine and NNTA content of e-cigarettes. Dependence and concurrent use of e-cigarettes and cigarettes will be assessed by a battery of self-report, biochemical, and behavioral indices. The findings from this project will have direct application to regulatory decision-making of the FDA. In so doing, the findings will facilitate the mission of FDA to effectively curb tobacco addiction and make "tobacco-related death and disease part of America's past."