Medicinal nicotine for preventing stress induced craving and withdrawal symptoms

描述(申请人提供)：尽管大多数吸烟者表示希望戒烟，但只有不到30%的吸烟者使用现有的治疗方法实现长期戒烟。烟草依赖的新治疗方法很少被采用，只有两种非尼古丁药理辅助手段可用。戒烟成功率低，新疗法的引入也很少，这就需要最大限度地发挥现有疗法的疗效。尼古丁含片通常被建议在需要的基础上使用，吸烟者通常被告知在出现渴望或戒断症状时使用尼古丁含片。然而，尼古丁浓度直到尼古丁含片使用约10分钟后才显著增加，并在开始使用约30分钟后达到峰值。对于经历渴望或戒断的急性症状的受试者来说，这种延迟可能太长了，无法防止复发。在实验室研究和自然主义研究中，有许多吸烟的触发因素已经被证明可以增加对吸烟的渴望，从而在吸烟之前减少吸烟。人们最常提到的两个吸烟诱因之一就是处于紧张的环境中。目前尚不清楚，在面对一项有压力的任务之前服用尼古丁含片是否能缓解受试者在压力下经常经历的渴望增加。为了解决这个问题并确定应该使用尼古丁含片的时间范围(相对于应激源)，建议进行一项实验室研究，在该研究中，将在应激任务之前和之后测量渴望和戒断症状。每个受试者将有一个实验室疗程，在此期间，在应激源之后立即给予尼古丁含片(以接近目前推荐的NRT的使用--即在出现渴望和戒断症状之后)，并将被随机分配到一个实验室疗程，在此期间，将在a)紧接在应激源之前；b)10分钟；c)20分钟；或d)在应激源之前30分钟给予尼古丁含片。来自这项研究的数据确定了尼古丁含片的最佳服用时间框架，将用于随后的拨款申请，以评估咨询吸烟者在预期吸烟触发时使用尼古丁含片是否会导致比目前咨询吸烟者在需要时(即在渴望或戒断症状已经发生后)使用这些产品的戒烟率更高的做法。最终，这一系列研究将导致更有效地使用药用尼古丁和更高的戒烟成功率。 与公共健康相关：这项计划中的研究将确定在压力任务之前服用尼古丁含片是否可以缓解吸烟者在面临压力时出现的烟草渴望和戒烟症状的增加。这些信息可能会导致给吸烟者的何时应该使用尼古丁含片的说明发生变化，从而使其在帮助吸烟者成功戒烟方面更加有效。

DESCRIPTION (provided by applicant): Although most smokers indicate a desire to quit smoking, fewer than 30% achieve long term abstinence using currently available treatments. New treatments for tobacco dependence have been introduced rarely with only two non-nicotine pharmacological aids available. The low smoking cessation success rates and the infrequent introduction of new therapies necessitate that the efficacy of currently available therapies be maximized. Nicotine lozenge is often recommended to be used on an as needed basis with smokers generally told to use the nicotine lozenge when craving or withdrawal symptoms occur. Nicotine concentrations however do not increase substantially until about 10 minutes after nicotine lozenge use and do not peak until approximately 30 minutes after starting use. For subjects experiencing acute symptoms of craving or withdrawal, this delay may be too long to prevent relapse. There are a number of smoking triggers that have been demonstrated in laboratory studies to increase craving and in naturalistic studies to precede smoking lapses. One of the two most commonly cited smoking triggers is the presence of a stressful situation. It is not currently known if use of the nicotine lozenge prior to being exposed to a stressful task attenuates the increase in craving that subjects frequently experience during stress. To address this issue and to identify the time-frame (relative to the stressor) during which a nicotine lozenge should be used, a laboratory study is proposed in which craving and withdrawal symptoms will be measured prior and subsequent to a stress task. Each subject will have one laboratory session at which nicotine lozenge is given immediately after the stressor (to approximate current recommended use of NRT - i.e. after craving and withdrawal symptoms occur) and will be randomized to one laboratory session at which nicotine lozenge will be given either a) immediately prior to; b) 10 minutes; c) 20 minutes; or d) 30 minutes prior to the stressor. Data from this study identifying the optimal time-frame for nicotine lozenge administration will be used in a subsequent grant application to assess if counseling smokers to use nicotine lozenge in anticipation of a smoking trigger results in higher cessation rates than the current practice of counseling smokers to use these products when they need them (i.e. after symptoms of craving or withdrawal have already occurred). Ultimately this line of research should lead to more effective use of medicinal nicotine and higher smoking cessation success rates. PUBLIC HEALTH RELEVANCE: The planned study would determine if using nicotine lozenge prior to a stress task attenuates the increase in symptoms of tobacco craving and withdrawal that occurs when smokers are presented with stressful situations. Such information could lead to changes in the instructions given to smokers about when they should use nicotine lozenge, thereby making it more effective in helping smokers successfully quit.