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The Effect of Nicotine Delivery Rate on Reinforcement

The Effect of Nicotine Delivery Rate on Reinforcement

Principal Investigator: Kevin Jensen

Funding Mechanism: National Institutes of Health – Grant

ID number: 1R03DA043004-01

Award Date: 9/19/2016

Institution: Yale University


If e-cigarettes deliver nicotine at rates above a certain threshold, they can be addictive and potentially harmful, especially in nicotine-naïve users. In contrast, if the nicotine delivery rate of an e-cigarette falls below a critical threshold, it may have low addiction liability yet still provide sufficient nicotine to help smokers quit by reducing smoking urges and nicotine tobacco withdrawal symptoms. However, the critical rate of delivery that underlies the addictive effects of nicotine has yet to be empirically validated by controlled human studies. To close this knowledge gap, researchers will test nicotine reinforcement in 18 adult male and female smokers who will participate in a total of four experimental sessions involving different rates of nicotine administration. During experimental sessions, subjects will be given an intravenous (IV) nicotine infusion of either saline (as placebo) or 1 mg nicotine at rapid, moderate or slow infusion rates (nicotine at 0.24, 0.05 or 0.02 μg per kg body weight per second). The infusion conditions for each experimental session will be determined in a random order. Study aims are: (1) to establish a dose-effect curve for nicotine reinforcement as a function of nicotine delivery rate; (2) to establish a dose-effect curve for nicotine’s positive and negative subjective effects as a function of nicotine delivery rate; (3) to establish a dose-effect curve for nicotine’s ability to alleviate nicotine withdrawal symptoms in abstinent smokers as a function of nicotine delivery rate; and (4) to establish a dose-effect curve for nicotine’s acute cardiovascular health effects. Data from this project may help to establish benchmark values for nicotine’s threshold effects.