Affect, Context, and Placebo Responses to Nicotine

描述（由申请人提供）：安慰剂效应的系统性研究可以帮助我们更好地了解尼古丁依赖性，并可能为改变这些效应提供指导，以帮助人们戒烟，吸烟仍然是发病率和死亡率最重要的可预防原因。然而，尼古丁的研究很少包含安慰剂效应的研究，特别是平衡安慰剂设计。此外，关于药物使用情况和给药方法的背景如何影响任何药物的安慰剂效应，我们知之甚少。这两个因素可能对理解尼古丁摄入量至关重要。特别是，负面影响增强了对尼古丁的反应，并可能增强安慰剂效应，安慰剂效应可能取决于尼古丁是否在物质使用与药物使用背景下给药。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）。该项目几乎是第一个全面研究吸烟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消极情绪（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应的项目。我们将采用平衡安慰剂设计，在吸烟的物质使用背景下（研究1）和鼻喷雾剂NRT的药物使用背景下（研究2）系统地检查尼古丁的安慰剂效应。这些基于实验室的研究中的每一个都将在负面情绪和中性情绪中检查这些影响。我们还将评估安慰剂在几个方面的影响，除了自我报告的措施，包括面部影响的行为反应和声惊吓的心理生理反应。我们还将通过测量吸烟（研究1）或NRT（研究2）的自我给药来确定安慰剂效应是否延伸到实际药物使用行为（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，安慰剂效应将加强下，消极与中性的影响，我们将探讨这些影响是否不同的吸烟和NRT。结果将提高我们对尼古丁摄入安慰剂效应的背景影响的理解，特别是通过确定它们是否被个体的情感状态和药物摄入的形式改变。研究结果将为进一步研究背景因素提供方向，并可能为在吸烟的物质使用背景下对抗安慰剂效应和在NRT的药物使用背景下增强安慰剂效应提供途径。次要分析可以识别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获益最多。

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.