IV Pulsed-Nicotine as a Model of Smoking: The Effects of Dose and Delivery Rate

Seventy smokers will be randomized to nicotine doses of either 0.2 or 1 mg per 70 kg body weight. Across 5 test sessions, within each dose group, participants will be randomly assigned to a sequence of 5 treatment conditions: placebo (saline) and 4 different delivery rates of nicotine. In each session, participants will receive either nicotine- or saline-pulsed infusions that will be delivered every 30 seconds for a total of 10 pulsed infusions. While receiving the pulsed infusions, participants will inhale a tobacco-flavored EC without nicotine, which will allow for a closer matching of the sensory aspects of inhaled tobacco use. There are four pulse duration conditions for the nicotine sessions: 2-, 4-, 6- and 8-second pulses. For those assigned to 1.0 mg/70kg nicotine dose, the pulse duration conditions correspond to nicotine delivery rates of 50, 25, 16.6, and 12.5 mcg nicotine/second. For those assigned to 0.2 mg/70 kg dose, the corresponding delivery rates will be 10, 5, 3.3 and 2.5 mcg nicotine/second. Participants in both nicotine dose groups will each have one placebo test session wherein they will receive 10 pulsed-saline infusions.

Inclusion criteria

• Female and male, aged 21 to 55 years;
• past year daily cigarette use, verified by urine cotinine levels above 100 ng/ml -lifetime history of e-cigarette use; in good health as verified by medical history -screening examination, and screening laboratory tests
• women, -using acceptable birth control methods.

Exclusion criteria

• History of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the participant to be in the study
• risk factors for EVALI (E-cigarette or Vaping Product Use-Associated Lung Injury) including history of lung diseases (e.g., asthma or COPD), vaping THC or CBD
• regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
• current alcohol or substance use disorder for any other recreational or prescription drugs other than nicotine
• for women, pregnant as determined by pregnancy screening, or breast feeding
• seeking (or undergoing) treatment for tobacco dependence or smoking; reported aversion to e-cigarettes, or tobacco flavored e-liquid.