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

项目摘要。电子尼古丁输送系统（ENDS）加热并蒸发含尼古丁的液体 产生一种气雾剂，将尼古丁输送到血液和大脑中。ENDS被认为是烟草产品 在美国，受食品和药物管理局的监管。ENDS的使用有所增加 在过去的十年里，特别是在年轻人中，超过20%的美国高中生是目前的ENDS。 使用者，并且有证据表明这一人群中存在尼古丁依赖。联邦立法已经提出 这将限制ENDS液体尼古丁浓度，使ENDS“明显减少成瘾性和吸引力 青春”。然而，这些和其他通过限制尼古丁液体浓度来抑制成瘾的努力是不可能的 因为ENDS的尼古丁排放取决于多个变量。例如，尼古丁 由于尼古丁浓度有限，用户可以转向更高功率的ENDS设备以获得更多的尼古丁。实现 预期的公共卫生目标，针对成瘾的法规必须关注尼古丁的输送，而不是尼古丁 浓度.虽然尼古丁的释放不能直接调节，但ENDS释放尼古丁的速率， “尼古丁通量”可以被调节，并且重要的是，可以基于对一些基本原理的了解， 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， 流量和交付之间的关系，也不是流量和支持的生理和主观效果之间的关系， 尼古丁依赖缩小这一差距对于提供一个有效的、首要原则的框架至关重要， 调节结束。在目标1中，我们将研究尼古丁通量，尼古丁形式和速率之间的关系， 和尼古丁释放剂量。在耶鲁大学的临床实验室，参与者将在 在流量和形式不同的条件下，动脉血以高时间分辨率采样。结果会 表明尼古丁通量和形式决定ENDS尼古丁递送的速度和剂量的程度， 因此，滥用责任。在目标2中，我们将评估尼古丁通量、形式和主观症状之间的关系。 方面的影响.在贝鲁特的美国大学，参与者将使用具有不同尼古丁流量的ENDS设备， forms.将评估依赖性措施，如吸烟欲望、渴望和禁欲。成果 将指示尼古丁通量/形式影响与依赖性、抽吸相关的主观效应的程度 强度和暴露于有毒物质。总之，本项目将提供以下方面所需的经验证据： 公共卫生机构使用尼古丁通量作为一个涵盖和方便的结构来调节尼古丁 从终点出发。

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.