This project will examine the impact of the nicotine dose and delivery rate on nicotine's abuse potential, versus its potentially beneficial effects on smoking urges and withdrawal. Will use pulsed IV nicotine administration which closely matches nicotine delivery by inhaled tobacco use.

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.