Research Project 3 : Nicotine Delivery Rate and Its Abuse Potential: Impact of Menthol

研究项目 3：尼古丁输送率及其滥用潜力：薄荷醇的影响

基本信息

批准号：
10242020
负责人：
Mehmet Sofuoglu
金额：
$ 52.76万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-30 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10242020
关键词：
Address Affect Attenuated Behavior Behavioral Blood Pressure Body Weight Brain Characteristics Cigarette Cigarette Smoker Clinical Research Cotinine Crossover Design Dose Electronic Nicotine Delivery Systems Electronic cigarette Female Generations Goals Heart Rate Hour Human Infusion procedures Intravenous Measures Mediating Menthol Metabolism Methods Modeling Nicotine Nicotine Dependence Nicotinic Receptors Outcome Outcome Study Patient Self-Report Pharmaceutical Preparations Physiological Plasma Procedures Psychological reinforcement Randomized Research Project Grants Risk Saline Severities Sex Differences Smoke Smoker Smoking Symptoms Tobacco Tobacco Dependence Tobacco use Withdrawal Work addiction cigarette smoking cognitive performance combustible cigarette drug of abuse economic value experimental study hydroxycotinine interest male nicotine abuse placebo controlled study preclinical study recruit response smoking cessation tobacco products

项目摘要

Abstract: Project #3 Rapid delivery to the brain enhances the abuse potential of drugs of abuse, including nicotine. As proposed by Shihadeh and Eissenberg, “nicotine flux”, or the rate at which a given electronic cigarette (e-cigarette) delivers nicotine, is the most critical factor for evaluating its abuse potential. In this model, when an e-cigarette delivers nicotine at rates above a certain, yet undetermined, threshold it can have high abuse potential and may initiate or maintain tobacco addiction. In contrast, when the nicotine flux is optimal, that e-cigarette may have low addiction potential while providing sufficient nicotine delivery to help smokers quit smoking by alleviating urges to smoke. This proposed “optimal nicotine flux” concept has yet to be empirically assessed in controlled human studies. In addition, flavors and other e-cigarettes ingredients may also affect the impact of delivery rate on the addictive effects of nicotine. Most notably, menthol may have such an effect through inhibition of nicotinic receptors and slowing of nicotine metabolism. Systematic studies from our group and others have shown that intravenous (IV) nicotine infusion is an optimal approach for quantifying the influence of delivery rate on nicotine's behavioral and physiological effects. The primary aim of this project is to examine the impact of nicotine delivery rate on nicotine's abuse potential (assessed by positive subjective effects and reinforcement), and its potentially beneficial effects of alleviating smoking urges and withdrawal. We also seek to determine if switching from menthol to non-menthol cigarettes, modeling a ban on menthol cigarettes, changes the impact of nicotine delivery rate on the study outcomes. To reach these goals, we propose 2 placebo-controlled studies that will recruit male and female nicotine dependent smokers. Study 1 will recruit equal numbers of menthol (n=35) and non-menthol (n=35) preferring smokers for 5 experimental sessions, which will be at least 24 hours apart. Each session will include 1 randomly assigned infusion that will be either saline or a single dose of nicotine (1 mg per 70 kg body weight) delivered at 4 different infusion rates: 0.24, 0.096, 0.048 or 0.024 µg per kg body weight per second). The rates are within the range of nicotine delivery rates achieved by combustible and e-cigarettes and have been piloted in our recent study. In Study 2, menthol- preferring smokers (n=38) will be randomized to a sequence of menthol or non-menthol cigarette smoking conditions, each lasting for 2 weeks, using a crossover design. During week 2 of each period, 3 experimental sessions will be held on 3 separate days. The results from our application will help the FDA in establishing standards for nicotine delivery rates that minimize the addictive risks of e-cigarettes and other electronic nicotine delivery systems (ENDS).

摘要：项目#3 快速递送至大脑会增强滥用药物（包括尼古丁）的滥用可能性。 Shihadeh 和 Eissenberg 提出的“尼古丁通量”，或给定电子烟（电子烟）的速率在此模型中，尼古丁是评估电子烟滥用可能性的最关键因素。尼古丁的含量高于某个但尚未确定的阈值时，它可能具有很高的滥用潜力，并且可能会引发或维持烟草成瘾，相反，当尼古丁通量最佳时，电子烟可能会引发或维持烟草成瘾。成瘾潜力低，同时提供足够的尼古丁输送量，帮助吸烟者戒烟所提出的“最佳尼古丁通量”概念尚未得到实证评估。此外，香料和其他电子烟成分也可能影响效果。最值得注意的是，薄荷醇可能通过尼古丁的成瘾作用产生这种影响。抑制烟碱受体并减缓尼古丁代谢。其他人已经表明，静脉注射 (IV) 尼古丁输注是量化尼古丁影响的最佳方法。该项目的主要目的是检查尼古丁的行为和生理影响。尼古丁输送率对尼古丁滥用潜力的影响（通过积极的主观效应和强化），以及其减轻吸烟冲动和戒烟的潜在有益效果。确定是否从薄荷醇香烟转向非薄荷醇香烟，模拟薄荷醇香烟禁令，改变尼古丁输送率对研究结果的影响为了实现这些目标，我们提出 2。将招募男性和女性尼古丁依赖吸烟者的安慰剂对照研究研究 1 将招募男性和女性尼古丁依赖吸烟者。在 5 次实验中，偏好吸烟者的薄荷醇 (n=35) 和非薄荷醇 (n=35) 的数量相同，每个疗程将至少间隔 24 小时，其中包括 1 次随机分配的输液。盐水或单剂量尼古丁（每 70 公斤体重 1 毫克）以 4 种不同的输注速度输送：0.24、每秒每公斤体重 0.096、0.048 或 0.024 微克）。在我们最近的研究 2 中，薄荷醇- 已实现了可燃烟和电子烟所达到的比率。偏好吸烟者 (n=38) 将被随机分配到吸烟薄荷醇或非薄荷醇香烟的序列条件，每个持续 2 周，使用交叉设计，在每个周期的第 2 周进行 3 个实验。会议将分 3 天举行，我们的申请结果将帮助 FDA 确定。尼古丁输送率标准，可最大限度地减少电子烟和其他电子产品的成瘾风险尼古丁输送系统（ENDS）。