The 2009 Family Smoking Prevention and Tobacco Control Act gave the FDA authority to reduce public health harms of tobacco products. A key proposal is mandating nicotine reduction in cigarettes. It is hypothesized that reducing nicotine content will mitigate the overwhelming morbidity associated with smoking by decreasing smoking initiation and increasing cessation rates among established smokers. Clinical trials have provided promising support by demonstrating reductions in toxicant exposure and nicotine dependence for individuals randomized to reduced-nicotine cigarette conditions. Experimental work on reduced-nicotine cigarette pharmacodynamics has almost exclusively used blinded conditions, precluding systematic evaluation of how expectations about reduced-nicotine cigarettes may impact behavioral and subjective response. Given that real-world settings will involve unblinded products, information about expectancies is essential to inform how reduced-nicotine products will be perceived in future real-world markets. The proposed human laboratory study will systematically determine the independent and interactive effects of expectancy and nicotine dose on reinforcing (behavioral economic demand), subjective, and topography outcomes. Participants (10 men/women) in the proposed study will complete 4 experimental sessions in which expectancy (labeling of “average” nicotine versus “very low” nicotine) and nicotine dose (15.8 mg/g versus 0.4 mg/g) are manipulated as within-subject variables. Participants will smoke one study cigarette of these combinations at the start of each session and complete craving, mood, withdrawal, and subjective drug effect measures before and after smoking. Smoking topography will also be collected during cigarette administration to determine if expectancy and dose impact how one smokes – one way that cognitive or pharmacological effects can impact smoking behavior. Demand will be evaluated with an incentivized demand task using experienced outcomes to improve experimental rigor. Behavioral economic demand analyses will differentiate between effects attributable to consumption of a good at no or little cost (“demand intensity”) and consumption following increases in cost (“demand elasticity”). We hypothesize lower demand, subjective effects, and puff volume for “very low” labels and low nicotine dose cigarettes, with the lowest demand when in combination. This Behavioral Science Track Award for Rapid Transition (B/Start) R03 will provide critical information to the FDA on the reinforcing effects of smoking due to not only nicotine content, but nicotine expectancy – a factor that has received virtually no attention in nicotine reduction research. Identifying the specific behavioral mechanisms impacted by these factors is relevant as each have very different public health implications (e.g., impacts specific to demand intensity but not demand elasticity indicate that policy targeting cost changes would have minimal impact). ...