Improved Human Screening of Cessation Medications

目前的戒烟治疗大多数时候都是失败的，迫切需要强大的新治疗方法，包括药物。由于临床试验涉及大量的费用和时间，这些试验的药物必须是那些最有希望成功的药物。药物筛选研究的目的是快速和廉价地评估药物的临床潜力，以便有希望的药物进行临床试验，而没有希望的药物则不会。然而，在使用这些药物的临床试验中，没有药物的人体筛选程序，其结果可以明确预测戒烟结果。该提案旨在改进在对这些药物的疗效进行临床试验之前对潜在戒烟药物进行人体筛选的程序。 从逻辑上讲，对戒烟药物的人体筛选研究应该在实际限制范围内模拟临床试验程序。因此，应强调戒烟作为药物反应的主要指标，因为没有其他明确的长期戒烟的短期预测因素。我们将研究两种方法对药物作用的敏感性，这两种方法用于增加参加短期筛选研究的吸烟者戒烟的动机和可能性：1）？自然？由于参与者寻求治疗状态而产生的动机，以及2）？人工支持？使用金钱奖励的动机取决于戒烟。我们将评估160名寻求治疗的吸烟者和160名非寻求治疗的吸烟者，其中一半人将在戒烟（通过吸入空气CO <= 8 ppm验证）的基础上每天接受货币加固，另一半人将不会接受戒烟加固。在这些组中，我们将比较5天的效果？暴露于21 mg尼古丁与安慰剂贴剂，使用受试者内交叉设计。我们的主要依赖措施将是戒烟天数和连续5天戒烟 （二分结果），吸烟/天，渴望，戒断，负面影响和ADHD症状作为次要指标。我们假设尼古丁与安慰剂贴剂之间的差异在寻求治疗者中比非寻求者更大，在接受禁欲强化与未强化的患者中更大。其次，我们将研究 尼古丁效应的大小作为5天治疗期内各天药物暴露持续时间的函数，以确定早期药物效应的峰值点。将在自然环境和实验室中进行自我报告措施的评估，以确定评估方法对药物反应的影响。我们将 还研究了尼古丁反应的个体差异。结果将为改善戒烟药物的筛选评估提供直接指导。未来的方向包括测试这种改进的筛查程序与新型药物的效用，长期目标。这项研究最终将帮助我们更好地了解如何更快地 并有效地评估潜在的戒烟药物，这是一个具有非常高的公共卫生意义的目标。

Current treatments for smoking cessation fail most of the time, and robust new treatments, including medications, are sorely needed. Because ofthe substantial costs and time involved in clinical trials, medications subjected to these trials must be those with the greatest promise of success. The purpose of medication screening studies is to quickly and cheaply evaluate the clinical potential of medications, so that promising drugs proceed to clinical trials and unpromising drugs do not. However, there is no human screening procedure for medications in which results are clearly predictive of smoking cessation outcome in clinical trials with those medications. This proposal aims to improve procedures for human screening of potential medications for smoking cessation prior to clinical trials of the efficacy of those medications. Logically, studies on human screening of cessation medications should simulate, within practical limitations, clinical trial procedures. Thus, emphasis should be placed on smoking abstinence as the primary index of medication response, as there are no other clear short-term predictors of long-term abstinence. We will examine sensitivity to medication effects as a function of two methods used to increase the motivation and likelihood of abstinence in smokers participating in a short-term screening study: 1) ?natural? motivation due to treatment seeking status of participants, and 2) ?artificially supported? motivation using monetary incentives contingent on smoking abstinence. We will assess 160 treatment-seeking smokers and 160 non-treatment seeking smokers, half of whom will receive monetary reinforcement on a daily basis contingent on being abstinent (verified by expired-air Co <= 8 ppm) and half of whom will not receive reinforcement far abstinence. In these groups, we will compare effects of 5 days? exposure to 21 mg nicotine versus placebo patch, using a within-subjects cross-over design. Our main dependent measures will be days of smoking abstinence and continuous 5-day abstinence (dichotomous outcome), with cigarettes/day, craving, withdrawal, negative affect, and ADHD symptoms as secondary measures. We hypothesize that differences between nicotine vs placebo patch will be greater in treatment seekers than non-seekers, and in those receiving abstinence reinforcement vs no reinforcement. Secondarily, we will examine changes in the magnitude of nicotine effects as a function ofthe duration of exposure to medication across days within the 5-day treatment period, to identify the point of peak early medication effects. Assessment of self-report measures will be conducted in the natural environment, as well as the lab, to determine the influence of method of assessment on medication response. We will also examine individual differences in nicotine responses. Results will provide immediate directions for improving screening evaluations of cessation medications. Future directions include testing the utility of this improved screening procedure with novel medications, the long-range objective. This research will ultimately help us better understand how to more quickly and efficiently evaluate potential medications for smoking cessation, a goal with very high public health significance.