Differential effects of nicotine delivery rate on subjective drug effects, urges to smoke, heart rate and blood pressure in tobacco smokers.

Abstract

The nicotine delivery rate is a key feature of tobacco product design, yet there have been limited human studies examining the effects of nicotine as a function of delivery rate. We developed an intravenous nicotine infusion protocol to evaluate differential effects of nicotine delivery rate on subjective drug effects, smoking urges, abstinence symptoms, heart rate, and blood pressure. Eighteen non-treatment seeking, overnight abstinent male and female smokers (18 to 30years old), who smoked ≥ 5 cigarettes per day for the past year completed four sessions, in which they were randomly assigned to a saline infusion, or a 1mg per 70-kg body weight dose of nicotine delivered over 1, 5, or 10min at rates of 0.24, 0.048, or 0.024μg/kg/s, respectively. Smoking urges, as assessed by the Brief Questionnaire of Smoking Urges, were reduced relative to placebo for the 1- and 5-min infusion, but not the 10-min infusion. Although the 1- and 5-min infusions reduced smoking urges to a similar extent, the 1-min infusion induced a greater heart rate and blood pressure increase. Changes to subjective drug effects, heart rate, and blood pressure delineate the differential effects of nicotine delivery rate for these outcomes. We have characterized the delivery rate-response curve for a nicotine dose that is roughly the amount of nicotine (~ 1mg) delivered by smoking a standard tobacco cigarette. Our findings reinforce the importance of nicotine delivery rate when evaluating the potential effects of nicotine from tobacco products.