Nicotine flux, a potentially powerful tool for regulating nicotine delivery from electronic cigarettes: significance of nicotine flux to the rate of nicotine delivery and subjective effects

项目总结。电子尼古丁输送系统(END)加热和汽化含有尼古丁的液体 产生一种可以将尼古丁输送到血液和大脑的气雾剂。烟头被认为是烟草产品 在美国，受美国食品和药物管理局的监管。终端使用量增加 在过去十年中迅速增长，特别是在年轻人中：超过20%的美国高中生是目前的终结者 而且有证据表明，这一人群对尼古丁有依赖。已经提出了联邦立法 这将限制Ends的液态尼古丁浓度，以使Ends“显著降低成瘾性和吸引力” 为青春干杯。然而，这些和其他通过限制尼古丁液体浓度来遏制成瘾的努力是不太可能的 因为烟头的尼古丁排放取决于多个变量，所以才能成功。例如，尼古丁 浓度有限，用户可以求助于功率更高的终端设备来获得更多尼古丁。要实现 预期的公共卫生目标，针对成瘾的监管必须专注于尼古丁的传递，而不是尼古丁 集中精神。虽然尼古丁的传递不能直接受到监管，但烟头释放尼古丁的速度， “尼古丁流量”是可以调节的，而且更重要的是，可以根据一些知识根据第一性原理进行预测。 设备设计和操作变量。然而，到目前为止，还没有经验证据表明 通量和释放之间的关系，通量和支持的生理和主观效应之间的关系 尼古丁依赖。缩小这一差距对于提供一个有效的首要原则框架至关重要 调节的目的。在Aim1中，我们将检查尼古丁流量、尼古丁形式和比率之间的关系 和尼古丁注射剂量。在耶鲁大学的临床实验室里，参与者将在 不同流量和形态的条件，同时以高时间分辨率采集动脉血液。结果将是 指出尼古丁流量和形态决定尼古丁末端输送速度和剂量的程度， 因此，滥用责任。在AIM2中，我们将评估尼古丁流量、形态和主观因素之间的关系 效果。在贝鲁特美国大学，参与者将使用具有不同尼古丁流量和 表格。将评估依赖措施，如吸烟的冲动、渴望和禁欲。结果是 将指示尼古丁流量/形式对与依赖、吸烟相关的主观效果的影响程度 强度和暴露在毒物中。总而言之，该项目将提供所需的经验证据 公共卫生机构将尼古丁流动作为一种包罗万象和方便的结构来调节尼古丁 从末端送货。

Project summary. Electronic nicotine delivery systems (ENDS) heat and vaporize a nicotine-containing liquid to produce an aerosol that can deliver nicotine to the blood and the brain. ENDS are considered tobacco products in the US and are under the regulatory authority of the Food and Drug Administration. ENDS use has increased rapidly in the last decade, especially among youth: over 20% of US high school students are current ENDS users, and there is evidence of nicotine dependence in this population. Federal legislation has been proposed that would restrict ENDS liquid nicotine concentration to make ENDS “significantly less addictive and appealing to youth.” However, these and other efforts to curb addiction by limiting nicotine liquid concentration are unlikely to succeed because nicotine emissions from ENDS depend on multiple variables. For example, where nicotine concentration is limited, users can turn to a higher power ENDS device to attain more nicotine. To achieve the intended public health aims, regulations targeting addiction must focus on nicotine delivery, not nicotine concentration. While nicotine delivery cannot be regulated directly, the rate at which an ENDS emits nicotine, the “nicotine flux” can be regulated and, importantly, predicted from first-principles based on knowledge of a few device design and operating variables. However, to date there is no empirical evidence demonstrating the relationship between flux and delivery, nor between flux and the physiological and subjective effects that support nicotine dependence. Closing this gap is essential for providing an effective, first-principles framework for regulating ENDS. In Aim1, we will examine the relationship between nicotine flux, nicotine form, and the rate and dose of nicotine delivery. In the clinical lab at Yale University, participants will puff on ENDS devices under conditions that differ by flux and form, while arterial blood is sampled in high time resolution. The outcome will indicate the degree to which nicotine flux and form determine the speed and dose of ENDS nicotine delivery, and thus, abuse liability. In Aim2, we will assess the relationship between nicotine flux, form, and subjective effects. At the American University of Beirut, participants will use ENDS devices with varying nicotine fluxes and forms. Dependency measures, such as urge to smoke, craving, and abstinence, will be assessed. The outcome will indicate the degree to which nicotine flux/form influence subjective effects related to dependency, puffing intensity, and exposure to toxicants. In summary, this project will provide the empirical evidence needed for public health agencies to use nicotine flux as an encompassing and convenient construct to regulate nicotine delivery from ENDS.