Dose effects of nicotine: Behavioral economics of cigarette abuse liability

2009年《家庭吸烟预防和烟草控制法案》授权FDA限制香烟尼古丁 级别。有人主张强制减少香烟，以降低尼古丁的水平 依赖，从而提高戒烟率，降低压倒性的发病率和 与吸烟有关的死亡率(Benowitz和Henningfield，1994)。研究表明， 尼古丁香烟导致尼古丁摄入量减少(Benowitz等人)。2007年；Donny等人，2015)，并减少 尼古丁依赖(Donny等人，2015年)。然而，关于滥用-责任的关键问题仍然存在 减少尼古丁卷烟，暴露于减少尼古丁卷烟是否减少使用减少-和 全尼古丁香烟，减量尼古丁香烟是否会取代全尼古丁香烟，以及 这些潜在影响的剂量效应。减少尼古丁香烟的成瘾效应和滥用倾向， 因此，都没有得到很好的理解。这项双盲研究将系统地确定滥用的责任 与使用行为经济学滥用的标准全尼古丁香烟相比，减少尼古丁香烟- 责任法。这项针对100名(50名男性/女性)未接受治疗的依赖型吸烟者的拟议研究将 确定减少尼古丁香烟与全尼古丁香烟相比的滥用倾向 行为经济学滥用-责任方法。卷烟消耗量的实验室测定 在6周的在家暴露之前和之后，参与者将有不同的反应要求 随机分为全烟(15.8毫克尼古丁/克烟草)或不同水平的减量尼古丁香烟(5.2、2.4和 1.3毫克/克)，以确定经验对减少尼古丁香烟的滥用易感性的作用。滥用 负债将通过两个基本需求指标进行评估：较低的需求强度和增加的需求 弹性，以及其他需求指标和“喜欢”的主观评级。这项研究还将确定 低尼古丁香烟替代全尼古丁香烟的程度--测试 减少尼古丁的政策将实现减少全尼古丁香烟消费的目标。通过检查 尼古丁的剂量效应，这项研究还将确定尼古丁的“成瘾阈值”，低于这个阈值的滥用-- 负债和尼古丁依赖减少。我们假设滥用减少的和全部的尼古丁的责任 香烟在接触减量尼古丁6周后会减少，但不会减少全量尼古丁香烟。我们 假设减量尼古丁香烟将取代全尼古丁香烟 曝光期延长，但替代性程度会有所提高。关于剂量效应，我们 假设与5.2和5.2相比，2.4和1.3毫克/克的暴露会减少滥用倾向 15.8毫克/克香烟。我们假设需求曲线指标的结果(强度降低 需求和弹性的增加)将显示出显著的，但温和的相关性下降的评级“喜欢”。 这项研究将通过先进的经验滥用责任测试为烟草公共政策提供实质性的信息。

The Family Smoking Prevention and Tobacco Control Act 2009 gave FDA authority to limit cigarette nicotine levels. Arguments have been made for mandating a reduction in cigarettes in order to reduce levels of nicotine dependence and therefore increase smoking cessation rates and decrease the overwhelming morbidity and mortality associated with smoking (Benowitz and Henningfield, 1994). Studies have suggested reduced nicotine cigarettes result in decreased nicotine intake (Benowitz et al. 2007; Donny et al., 2015) and decreased nicotine dependence (Donny et al., 2015). However, critical questions remain regarding the abuse-liability of reduced nicotine cigarettes, whether exposure to reduced nicotine cigarettes reduces use in both reduced- and full-nicotine cigarettes, whether reduced-nicotine cigarettes will substitute for full-nicotine cigarettes, and the dose-effects of these potential effects. The addictive effects and abuse liability of reduced nicotine cigarettes, therefore, are not well understood. This double-blind study will systematically determine the abuse liability of reduced-nicotine cigarettes compared to standard full-nicotine cigarettes using a behavioral economics abuse- liability approach. The proposed study in 100 (50 men/women) non-treatment seeking dependent smokers will determine the abuse liability of reduced-nicotine cigarettes compared to full-nicotine cigarettes using a behavioral economics abuse-liability approach. Laboratory determination of cigarette consumption under various response requirements will occur before and after 6 weeks of at-home exposure, with participants randomized to full (15.8 mg nicotine/g tobacco) or varying levels of reduced nicotine cigarettes (5.2, 2.4, and 1.3 mg/g) to determine the role of experience on the abuse-liability of reduced nicotine cigarettes. Abuse liability will be assessed by 2 essential demand metrics: lower demand intensity and increased demand elasticity, as well as other demand metrics and subjective ratings of “liking”. The study will also determine the degree to which reduced-nicotine cigarettes may substitute for full-nicotine cigarettes – testing whether a reduced-nicotine policy would achieve the goal of reducing full-nicotine cigarette consumption. By examining nicotine dose-effects, the study will also determine a nicotine “addictiveness threshold” below which abuse- liability and nicotine dependence decreases. We hypothesize that abuse liability of reduced- and full-nicotine cigarettes will be decreased after 6-weeks exposure to reduced-nicotine, but not full-nicotine cigarettes. We hypothesize that reduced-nicotine cigarettes will substitute for full-nicotine cigarettes both before and after the exposure period, but there will be an increase in the degree of substitutability. Regarding dose effects, we hypothesize that reduced abuse liability will be observed with exposure to 2.4 and 1.3 mg/g relative to 5.2 and 15.8 mg/g cigarettes. We hypothesize that results with demand curve metrics (decreases in intensity of demand and increases in elasticity) will show significant but modest correlations to decreased ratings of “liking.” This study stands to substantially inform tobacco public policy with advanced empirical abuse-liability testing.