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.
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