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Development of pulsed intravenous nicotine infusions as a model for inhaled nicotine in humans
Joao P De Aquino1,2, Elise E DeVito3,4, Catherine Xie3,4
1Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, USA. joao.deaquino@yale.edu.
Rationale:
Although nicotine from cigarettes is delivered in puff-sized amounts, most preclinical and human intravenous (IV) nicotine studies have used bolus or continuous infusions.
Objectives:
To determine the feasibility of a pulsed-nicotine infusion model in smokers.
Methods:
Following overnight abstinence, 12 adult smokers underwent 5 laboratory sessions. Using a crossover design, in each session, participants were assigned to 1 of 5 conditions: (1) high/fast: 1.0 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (2) high/slow: 1.0 mg nicotine delivered over 20 pulsed-infusions; (3) low/fast: 0.2 mg nicotine delivered over 5 pulsed-infusions, then 15 saline infusions; (4) low/slow: 0.2 mg nicotine delivered over 20 pulsed-infusions; and (5) placebo: Saline delivered over 20 pulsed-infusions. Subjective drug effects, urges to smoke, nicotine withdrawal, and cognitive performance were measured in each session.
Results:
Both the high/fast and high/slow conditions were associated with greater "head rush" and "high" (p < 0.05). The high/fast condition also provided greater suppression of urges to smoke and nicotine withdrawal (p < 0.05), indexed by the Questionnaire of Urges to Smoke-Brief, and the Minnesota Nicotine Withdrawal Scale, respectively. The high/fast and high/slow conditions produced greater increases in heart rate (p < 0.01) than saline. Finally, there were no main effects of dosing conditions on cognitive performance, indexed by the continuous performance test.
Conclusions:
These findings demonstrate the feasibility of pulsed-nicotine infusions to model nicotine delivery by smoking. This model could inform future studies testing novel smoking cessation therapies and tobacco regulatory studies testing the impact of nicotine reduction approaches.
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