Cigarette Harm Reduction with Scheduled Electronic Cigarette Use

项目摘要/摘要 使用电子烟(EC)的主要原因之一是减少吸烟的危害。危害 使用EC的减少可以通过减少每天吸食传统烟草香烟(TC)来实现，或者 从TC完全切换到EC。到目前为止，关于使用EC对健康影响的数据相对较少 为了减少伤害。 我们实验室已经对ECS的临床药理学和毒理学进行了几年的研究 好几年了。我们的方法是深入调查使用行为、化学暴露和生物 在仅限于研究病房环境的受试者中，EC与TC使用的效果比较。我们建议使用类似的 利用新开发的NIDA标准化工具研究减害问题的研究方法 研究电子烟(SREC)。 我们的总体目标有两个：(1)比较尼古丁和毒物的暴露及其药理作用 SREC单独使用VS TC；以及(2)使用预定的SREC使用和临时TC使用作为 两用，以检查尼古丁和毒物暴露的程度和潜在危害的生物标记物 请比较双重使用与单独使用TC。前者将告知完全转换的影响，后者将 告知在使用EC的同时减少吸烟TC的潜在危害效果。 熟悉EC使用的日常吸烟者将被指示仅使用SREC和TC，分别为一种 每周一次。在第三周，他们将被指示按计划每天使用SREC 8次，并且是免费的 否则，根据需要使用SREC或TC。每周的最后三天，受试者将被限制在 提供给临床研究单位，以确保严格遵守产品使用以及密集的数据和生物检疫 收集。我们将：(1)检查SREC作为尼古丁输送装置，包括尼古丁的个体变异性 尼古丁的摄入量和药代动力学、使用的时间模式和滴定，与TC使用的比较；(2) 检查SREC使用的主观影响，包括使用模式和程度与尼古丁水平的关系 奖励、戒断和渴求，与使用TC进行比较；(3)检查SREC使用的安全性方面(通过 评估使用对心血管和激素的影响以及暴露于潜在有毒物质的生物标记物 (4)比较尼古丁和毒物的暴露、主观影响以及心血管和荷尔蒙 单独使用TC与双重使用SREC/TC的影响(减少危害评估)和(5)验证可能 有助于区分EC和TC的用法。 拟议的研究将提供有关SREC的临床药理学和毒理学的重要信息， 以及在双重使用SREC以减少不良反应的支持下，每天减少吸烟的可能性 单独使用TC对心血管健康的影响。

PROJECT SUMMARY/ABSTRACT One of the major reasons cited for the use of electronic cigarettes (EC) is to reduce harm from smoking. Harm reduction using EC might be accomplished by smoking fewer conventional tobacco cigarettes (TC) per day, or switching completely form TC to EC. To date there are relatively few data on health consequences of EC use for harm reduction. Our laboratory has been conducting research on the clinical pharmacology and toxicology of ECs for several years. Our approach has been intensive investigation of use behaviors, chemical exposures and biological effects of EC compared to TC use in subjects confined to a research ward setting. We propose to use a similar research approach to study harm reduction questions with the use of the newly-developed NIDA Standardized Research E-cigarette (SREC). Our overall goals are two-fold: (1) to compare nicotine and toxicant exposure and pharmacological effects of SREC used alone vs TC; and (2) using scheduled SREC use combined with ad libitum TC use as a model for dual use, to examine the extent to which nicotine and toxicant exposure and biomarkers of potential harm compare with dual use vs TC alone use. The former would inform the effects of total switching, the latter would inform the potential harm reducing effects of smoking fewer TC while using EC. Daily cigarette smokers who are familiar with EC use will be instructed to use only SREC and TC, each for one week at time. On a third week they will be instructed to use SREC on a schedule 8 times per day, and be free otherwise to use either SREC or TC as desired. For the last three days of each week, subjects will be confined to a clinical research unit to ensure strict compliance with product use and for intensive data and biospecimen collection. We will: (1) examine SREC as a nicotine delivery device, including individual variability in nicotine intake and pharmacokinetics, temporal patterns of use and titration of nicotine, compared to TC use; (2) examine subjective effects of SREC use, including relationship of pattern and extent of use and nicotine levels to reward, withdrawal and craving, with comparison to TC use; (3) examine aspects of safety of SREC use (by assessment of cardiovascular and hormonal effects of use and of biomarkers of exposure to potentially toxic constituents); (4) compare nicotine and toxicant exposure, subjective effects and cardiovascular and hormonal effects of TC alone vs dual SREC/TC use (harm reduction assessment) and (5) validate biomarkers that may be useful in distinguishing EC from TC use. The proposed research will provide essential information on the clinical pharmacology and toxicology of SREC, and on the potential for smoking fewer TC per day supported by dual use of SREC to reduce adverse cardiovascular health effects of TC use alone.