Impact of a reduced nicotine standard on young adult appeal for menthol and non-menthol cigarettes

本R01提案响应了RFA-OD-19-019中的优先领域#2（成瘾）和#4（行为）。尽管美国食品和药物管理局禁止在香烟中标明口味，但消费者仍然可以买到薄荷香烟。薄荷卷烟在年轻人（YA，这里定义为18-24岁）中有所增加，而非薄荷卷烟在这一年龄组中有所减少，大多数新青少年吸烟者开始吸食薄荷卷烟。与不含薄荷醇的香烟相比，薄荷醇香烟的实验更有可能发展为定期吸烟和尼古丁依赖。最近，美国食品和药物管理局（FDA）宣布了将香烟中的尼古丁含量降低到最低成瘾性或非成瘾性水平的意图。值得注意的是，降低尼古丁标准将适用于市场上的所有香烟，包括占香烟市场份额30%的薄荷香烟。薄荷醇令人愉悦的味道和其他感官效果（喉咙中的凉爽/舒缓的感觉）可能有助于积极的第一次吸烟体验，这是一种将开始与吸收和经常吸烟联系起来的潜在机制。因此，一个关键的悬而未决的问题是，尽管尼古丁含量很低，薄荷醇是维持还是增加了吸烟的强化特性。如果低尼古丁香烟（VLNC）吸烟的吸引力和强化特性通过添加薄荷醇香剂而增加，而不含薄荷醇香剂的低尼古丁香烟（VLNC）吸烟可能会促进新用户向常规吸烟的发展。虽然对照调查研究了吸烟VLNCs与NNCs的不同强化效应，但大多数研究都集中在已建立的成年吸烟者身上，而忽略了新吸烟者，而且很少（如果有的话）专门研究了吸烟薄荷脑与非薄荷脑VLNCs的不同吸引力。为了解决这一知识差距，我们将招募100名在过去6个月内开始定期吸烟的薄荷醇YA吸烟者，并使用经过验证的实验烟草市场（ETM）范式测量薄荷醇和非薄荷醇醇型VLNCs吸烟的吸引力/强化以及吸引力/强化对烟草购买行为的影响。呼吁/加强将通过两个互补的测量范式进行评估：一个在实验室，另一个在自然环境中使用生态瞬时评估（EMA）。实验室研究提供了大量的效率和内部控制，允许急性主观反应的因果推理；而EMA允许类似的行为因果排序，但以生态有效的形式。假设,而non-menthol VLNCs,薄荷醇/强化VLNCs将显示更大的吸引力,在实验室和通过EMA和吸引力将烟草购买行为和偏好预测模拟通过ETM“现实世界”。这项研究将分离出薄荷醇对吸烟的独特影响，而不是降低尼古丁标准，并将有助于在未来的研究中告知有关薄荷醇VLNCs滥用责任和其他烟草产品中使用香料的监管决定。

This R01 proposal is responsive to priority areas #2 (Addiction) and #4 (Behavior) within RFA-OD-19-019. Although the FDA banned characterizing flavors in cigarettes, menthol cigarettes are still available to consumers. Menthol cigarette smoking has increased specifically in young adults (YA; defined here as ages 18-24), while non- menthol smoking has decreased in this age group, and the majority of new YA smokers initiate with a menthol cigarette. Experimentation with menthol cigarettes vs non-menthol cigarettes, is linked to greater likelihood of progressing to regular smoking and of nicotine dependence. Recently, FDA has announced its intention to the reduce the nicotine in cigarettes to minimally addictive or non-addictive levels. Notably, a reduced nicotine standard would apply to all cigarettes on the market, including menthol cigarettes, which account for 30% of the cigarette market share. Menthol's pleasurable taste and other sensory effects (cooling /soothing sensations in the throat) may contribute to a positive first smoking experience, a potential mechanism linking initiation with uptake and regular smoking. As such, a key unanswered question is whether menthol sustains or increases the reinforcing properties of cigarette smoking in YAs, despite a low-nicotine product standard. If the appeal and reinforcing properties of very low nicotine cigarette (VLNC) smoking is increased by menthol flavoring in YAs, beyond non-menthol VLNC smoking, this may facilitate progression to regular smoking among newer users. While controlled investigations have examined the differential reinforcing effects of smoking VLNCs vs NNCs, the majority have focused on established adults smokers but omitted YA new smokers, and few, if any, have specifically examined differential appeal for smoking menthol vs non-menthol VLNCs. To address this knowledge gap, we will recruit 100 menthol YA smokers who started smoking regularly in the past 6-months, and measure appeal/reinforcement for smoking both menthol and non-menthol VLNCs and the impact of appeal/reinforcement on tobacco purchasing behavior using a well-validated Experimental Tobacco Marketplace (ETM) paradigm. Appeal/reinforcement will be assessed via two complementary measurement paradigms: one in the laboratory and the other in the natural environment using ecological momentary assessment (EMA). Laboratory studies provide a great deal of efficiency and internal control, allowing for causal inference of acute subjective response; while EMA allows for similar causal sequencing of behavior, but in an ecologically valid format. It is hypothesized that, compared to non-menthol VLNCs, menthol VLNCs will show greater appeal/reinforcement, both in the laboratory and via EMA, and appeal will predict tobacco purchasing behavior and preferences simulated in the “real world” via the ETM. This research will isolate the unique effects of menthol in smoking, beyond a reduced nicotine standard, and will help inform regulatory decisions about the abuse liability of menthol VLNCs and the use of flavors in other tobacco products in future studies.