Affect, Context, and Placebo Responses to Nicotine

描述(申请人提供)：对安慰剂效应的系统研究可以帮助我们更好地了解尼古丁依赖，并可能为改变这些效应提供方向，以帮助人们戒烟，吸烟仍然是最重要的可预防的发病率和死亡率原因。然而，尼古丁研究很少包含安慰剂效应的研究，特别是关于平衡安慰剂设计的研究。此外，人们对药物使用情况和给药方法如何影响任何药物的安慰剂效果知之甚少。这两个因素可能对理解尼古丁摄入量至关重要。特别是，负面情绪增强了对尼古丁的反应，并可能增强安慰剂效果，安慰剂效果可能取决于尼古丁是在物质使用还是药物使用的情况下使用。尼古丁为研究药物制剂的影响提供了难得的机会，因为它被广泛用作滥用物质(吸烟)和药物(尼古丁替代疗法，NRT)。这个项目实际上将是第一个全面研究吸烟中的安慰剂效应以及另一种形式的尼古丁(NRT)的项目。此外，据我们所知，这个项目将是第一个研究负面情绪(特别是抑郁情绪)的关键情境如何改变任何药物的安慰剂效果的项目。我们将采用平衡安慰剂设计，系统地研究尼古丁在吸烟的物质使用环境(研究1)和鼻喷雾NRT的药物使用环境(研究2)中的安慰剂效果。这些基于实验室的研究中的每一项都将检验负面情绪和中性情绪中的这些影响。除了自我报告之外，我们还将评估几个维度的安慰剂效应，包括面部情感的行为反应和声音惊吓的心理生理反应。我们还将通过测量吸烟的自我管理(研究1)或NRT(研究2)来确定安慰剂效应是否延伸到实际的药物使用行为(即强化)。我们的主要目标是更清楚地了解影响这些安慰剂效应的发生和程度的背景因素。我们假设安慰剂效应在负面情绪和中性情绪下会增强，我们将探索这些效应在吸烟和NRT之间是否有所不同。结果将加强我们对尼古丁摄入中安慰剂效应的背景影响的理解，特别是通过确定这些影响是否会被个人的情感状态和药物摄入的形式改变。这些发现将为进一步研究背景因素提供方向，并可能为如何在吸烟的物质使用环境中对抗安慰剂效应，以及在NRT的药物使用环境中增强安慰剂效应提供方向。二次分析可能确定与安慰剂反应相关的重要个体特征，有助于预测哪些吸烟者最终可能从安慰剂效应的操纵中受益最大。

DESCRIPTION (provided by applicant): Systematic study of placebo effects could help us better understand nicotine dependence and, perhaps, provide directions for altering these effects to help people quit smoking, still the most important preventable cause of morbidity and mortality. However, nicotine research contains very few studies of placebo effects, particularly with the balanced-placebo design. Also, little is known about how the contexts of the drug use situation and method of drug administration influence placebo effects with any drug. Both factors may be critical to understanding nicotine intake. In particular, negative affect enhances responses to nicotine and may enhance placebo effects, and placebo effects may depend on whether nicotine is administered in the substance use versus medication use context. Nicotine offers a rare opportunity to study the influence of drug formulation since it is widely used both as a substance of abuse (smoking) and as a medication (nicotine replacement therapy, NRT). This project will be virtually the first to comprehensively examine placebo effects in smoking, as well as another form of nicotine (NRT). Moreover, to our knowledge, this project will be the first to examine how the critical situational context of negative affect (specifically depressed mood) alters the placebo effects of any drug. We will employ the balanced-placebo design to systematically examine the placebo effects of nicotine within the substance use context of cigarette smoking (study 1) and within the medication use context of nasal spray NRT (study 2). Each of these lab-based studies will examine these effects during negative affect and neutral affect. We will also assess placebo effects across several dimensions, aside from self-report measures, including the behavioral response of facial affect and the psychophysiological response of acoustic startle. We will also determine whether placebo effects extend to actual drug use behavior (i.e. reinforcement) by measuring self-administration of smoking (study 1) or NRT (study 2). Our main goal is to more clearly understand the contextual factors that influence the occurrence and magnitude of these placebo effects. We hypothesize that placebo effects will be enhanced under negative versus neutral affect, and we will explore whether these effects differ between smoking and NRT. Results will enhance our understanding of contextual influences on placebo effects in nicotine intake, specifically by determining whether they are altered by the affective state of the individual and by the form of drug intake. Findings will provide directions for further research into contextual factors and perhaps into avenues for countering placebo effects in the substance use context of smoking and for enhancing placebo effects in the medication use context of NRT. Secondary analyses may identify important individual characteristics associated with placebo responses, aiding in the prediction of which smokers ultimately are likely to benefit most from manipulation of placebo effects.