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: 10554395
• 负责人: AHMAD EL HELLANI
• 金额: $ 44.31万
• 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/10554395
• 关键词: Abstinence; Acute; Aerosols; American; Authorization documentation; Base Ratios; 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

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.

项目摘要。电子尼古丁输送系统（末端）加热并蒸发含尼古丁的液体 生产可为血液和大脑输送尼古丁的气溶胶。末端被视为烟草产品 在美国，在食品和药物管理局的监管机构下。结束使用增加了 在过去的十年中，尤其是在年轻人中迅速：超过20％的高中生是当前的目的 用户，并且有证据表明该人群中的尼古丁依赖性。已提出联邦立法 这将限制液态尼古丁的浓度，以使末端“添加剂明显降低并出现 然而，这些通过限制尼古丁液体浓度来遏制增加的努力是不太可能的 成功，因为末端的尼古丁排放取决于多个变量。例如，尼古丁 浓度有限，用户可以转向更高的功率端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集中于尼古丁的递送，而不是尼古丁 专注。虽然不能直接调节尼古丁的递送，但末端排放尼古丁的速率， 可以根据一些知识来调节“尼古丁通量”，并从第一原理进行调节 设备设计和操作变量。但是，到目前为止，还没有证据证明 通量与交付之间的关系，磁通与支持的物理和主观效应之间的关系 尼古丁依赖性。缩小此差距对于提供有效的第一原理框架至关重要 调节末端。在AIM1中，我们将研究尼古丁通量，尼古丁形式与速率之间的关系 和尼古丁递送的剂量。在耶鲁大学的临床实验室中，参与者将在末端设备上吐口水 通过通量和形式不同的条件，而动脉血液则以高时间分辨率采样。结果会 指示尼古丁通量和形式确定尼古丁递送的速度和剂量的程度， 因此，虐待责任。在AIM2中，我们将评估尼古丁通量，形式和主观的关系 效果。在贝鲁特美国大学，参与者将使用带有不同尼古丁通量的端设备， 表格。将评估依赖措施，例如吸烟，渴望和禁欲的冲动。结果 将指示尼古丁通量/形式影响与依赖关系相关的主观效应的程度 总而言之，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规范尼古丁的范围 从目的交付。