Impact of delivery rate on the acute response to intravenous nicotine: A human laboratory study with implications for regulatory science.

Faster delivery rate enhances the abuse potential of drugs of abuse, yet systematic studies on the impact of delivery rate on the acute effects of nicotine in humans are lacking. Using an intravenous (IV) nicotine infusion procedure that allows precise control of rate of delivery, we examined the impact of nicotine delivery rate on the positive subjective drug effects, smoking urges, withdrawal, heart rate, blood pressure and attention function in smokers. Twenty-four male and female (ages 21-35) dependent smokers attended five experimental sessions, following overnight abstinence from smoking. Using a crossover design, participants attended five sessions, where they were assigned to a random sequence of saline infusion or 1 mg nicotine delivered over 1, 2.5, 5 or 10 min at rates of 1, 0.4, 0.2 or 0.1 mg/min, respectively. The positive subjective effects of nicotine were most robust under the two faster delivery rate conditions, 1- and 0.4-mg nicotine/min. In contrast, all nicotine delivery rates were equally more effective than saline in alleviating urges to smoke. Likewise, nicotine-induced heart rate increases did not vary with the rate of nicotine delivery. Lastly, the cognitive enhancing effects of nicotine were observed only under the two slowest delivery rate conditions-0.1- and 0.2-mg nicotine/min. Collectively, these findings support the critical role of delivery rate in optimizing nicotine's abuse potential versus potential therapeutic effects and have timely implications for developing novel therapeutics for nicotine dependence, as well as for tobacco regulatory science.