Improved Human Screening of Cessation Medications

目前的戒烟疗法大多失败，迫切需要强有力的新疗法，包括药物治疗。由于临床试验涉及的大量成本和时间，接受这些试验的药物必须是那些最有希望取得成功的药物。药物筛选研究的目的是快速、廉价地评估药物的临床潜力，使有希望的药物进入临床试验，而没有希望的药物不进行临床试验。然而，在这些药物的临床试验中，没有对药物进行人体筛选的程序，在这些程序中，结果可以明显预测戒烟效果。这项提议旨在改进在对潜在戒烟药物的疗效进行临床试验之前对这些药物进行人体筛选的程序。 从逻辑上讲，戒烟药物的人体筛选研究应该在实际限度内模拟临床试验程序。因此，应该强调戒烟作为药物反应的主要指标，因为没有其他明确的短期预测长期戒烟的指标。我们将考察两种方法对药物效应的敏感性，这两种方法用于增加参加短期筛查研究的吸烟者的戒烟动机和可能性：1)自然？由于参与者寻求治疗的状态而产生的动机，以及2)？人为支持？以戒烟为条件的金钱激励。我们将评估160名寻求治疗的吸烟者和160名未寻求治疗的吸烟者，其中一半人将根据戒烟情况每天获得金钱补贴(由Expired-Air Co&lm=8ppm核实)，而其中一半人将不会获得戒烟后的强化。在这些组中，我们会比较5天的效果吗？使用受试者内部交叉设计，暴露于21毫克尼古丁与安慰剂贴片。我们的主要依赖措施将是戒烟天数和连续戒烟5天 (二分结果)，将吸烟/天、渴望、戒断、负面影响和ADHD症状作为次要指标。我们假设尼古丁贴片和安慰剂贴片之间的差异在寻求治疗的人中比在非寻求的人中更大，在接受戒酒强化的人和不接受强化的人中也是如此。其次，我们将检查 尼古丁效应的大小是在5天的治疗期间内暴露于药物的持续时间的函数，以确定早期药物效应的峰值。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。我们会 还要检查尼古丁反应的个体差异。研究结果将为改进戒烟药物的筛查评估提供直接指导。未来的方向包括用新的药物测试这种改进的筛查程序的效用，这是长期目标。这项研究最终将帮助我们更好地理解如何更快地 并有效地评估戒烟的潜在药物，这是一个具有非常高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.