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

尼古丁通量，调节电子烟尼古丁释放的潜在强大工具：尼古丁通量对尼古丁释放速率和主观效果的重要性

• 批准号: 10351168
• 负责人: AHMAD EL HELLANI
• 金额: $ 44.45万
• 依托单位: AMERICAN UNIVERSITY OF BEIRUT
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10351168
• 关键词: Abstinence; Acute; Aerosols; American; Behavior; Blood; Blood Circulation; Brain; Clinical; Computer Simulation; Dependence; Device Designs; Devices; Dose; Drug Kinetics; Electronic Nicotine Delivery Systems; Electronic cigarette; Encapsulated; Exposure to; High School Student; In Situ; Inhalation; Intuition; Knowledge; Left; Link; Liquid substance; Lung; Measures; Metabolic; Methods; Monitor; National Institute of Drug Abuse; Nicotine; Nicotine Dependence; Outcome; Participant; Performance; Physiological; Population; Psychological reinforcement; Public Health; Regulation; Reporting; Resolution; Resort; Risk; Robot; Sampling; Sensory; Smoke; Speed; Statutes and Laws; Study Subject; Testing; Time; Toxicant exposure; United States Food and Drug Administration; Universities; Venous; Youth; abuse liability; addiction; authority; base; craving; design; discrete time; experience; instrument; liquid nicotine; mathematical model; medical schools; nicotine craving; nicotine use; public health priorities; tobacco products; tool; toxicant; vapor

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.

项目总结。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 被视为烟草制品 在美国，并受食品和药物管理局的监管。 ENDS 使用量有所增加 过去十年中，特别是在年轻人中，这一数字迅速增长：超过 20% 的美国高中生目前处于 ENDS 状态 使用者，并且有证据表明该人群存在尼古丁依赖。联邦立法已提出 这将限制 ENDS 液体尼古丁浓度，使 ENDS“显着降低成瘾性和吸引力 到青春。”然而，通过限制尼古丁液体浓度来抑制成瘾的这些和其他努力不太可能 成功是因为 ENDS 的尼古丁排放量取决于多个变量。例如，尼古丁在哪里 由于浓度有限，用户可以转向更高功率的 ENDS 设备来获取更多的尼古丁。为了实现 预期的公共卫生目标，针对成瘾的法规必须关注尼古丁的传递，而不是尼古丁 专注。虽然尼古丁输送量无法直接调节，但电子尼古丁传送系统释放尼古丁的速率， “尼古丁通量”是可以调节的，重要的是，可以根据一些知识的第一原理进行预测 设备设计和操作变量。然而，迄今为止，还没有任何经验证据证明 通量与输送之间的关系，以及通量与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有效的首要原则框架至关重要 监管电子尼古丁传送系统。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 和尼古丁输送剂量。在耶鲁大学的临床实验室中，参与者将在以下条件下吸食 ENDS 设备： 不同流量和形式的条件，而动脉血以高时间分辨率采样。结果将 表明尼古丁通量和形式决定 ENDS 尼古丁输送速度和剂量的程度， 因此，滥用责任。在 Aim2 中，我们将评估尼古丁通量、形式和主观之间的关系 影响。在贝鲁特美国大学，参与者将使用具有不同尼古丁通量和 形式。将评估依赖性措施，例如吸烟冲动、渴望和戒烟。结果 将表明尼古丁通量/形式影响与依赖性、抽吸相关的主观效果的程度 强度和接触有毒物质。总之，该项目将提供所需的经验证据 公共卫生机构使用尼古丁通量作为一种包容且方便的结构来调节尼古丁 从 ENDS 交付。