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

本R 01提案响应RFA-OD-19-019中的优先领域#2（成瘾）和#4（行为）。尽管FDA禁止在香烟中添加香料，但消费者仍然可以买到薄荷醇香烟。薄荷醇香烟吸烟在年轻人（YA;在此定义为18-24岁）中特别增加，而非薄荷醇香烟吸烟在该年龄组中减少，并且大多数新YA吸烟者开始使用薄荷醇香烟。与非薄荷醇香烟相比，薄荷醇香烟的实验与更大的可能性进展到经常吸烟和尼古丁依赖有关。最近，FDA宣布打算将香烟中的尼古丁降低到最低成瘾或非成瘾水平。值得注意的是，降低的尼古丁标准将适用于市场上的所有卷烟，包括占卷烟市场份额30%的薄荷醇卷烟。薄荷的愉悦味道和其他感官效果（喉咙中的冷却/舒缓感觉）可能有助于积极的首次吸烟体验，这是一种将开始与吸收和定期吸烟联系起来的潜在机制。因此，一个关键的未回答的问题是，尽管有低尼古丁产品标准，但薄荷醇是否能维持或增加YAs中吸烟的增强特性。如果极低尼古丁香烟（VLNC）吸烟的吸引力和增强特性通过YA中的薄荷醇调味剂增加，超过非薄荷醇VLNC吸烟，这可能有助于新用户发展为常规吸烟。虽然对照研究已经检查了吸烟VLNC与NNCs的差异增强作用，但大多数研究都集中在已确定的成年吸烟者身上，但忽略了YA新吸烟者，很少（如果有的话）专门检查吸烟薄荷醇与非薄荷醇VLNC的差异吸引力。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，并使用经过充分验证的实验烟草市场（ETM）范例测量吸烟薄荷醇和非薄荷醇VLNC的吸引力/强化以及吸引力/强化对烟草购买行为的影响。上诉/加固将通过两个互补的测量范式进行评估：一个在实验室和其他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顺序，但在生态学上有效的格式。假设与非薄荷醇VLNC相比，薄荷醇VLNC将在实验室中和通过EMA显示出更大的吸引力/增强，并且吸引力将预测通过ETM在“真实的世界”中模拟的烟草购买行为和偏好。这项研究将分离出薄荷醇在吸烟中的独特作用，超越降低尼古丁标准，并将有助于在未来的研究中为有关薄荷醇VLNC滥用倾向和其他烟草产品中使用香料的监管决策提供信息。

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.