A placebo-controlled study to enroll male and female tobacco smokers who will participate in five experimental sessions. subjects will be given an IV infusion of either saline or 1 mg nicotine at rapid, moderate or slow infusion rates (nicotine at 0.24,0.096, 0.048 and 0.024, mcg per kg body weight per sec).

A placebo-controlled study that will enroll male and female tobacco smokers' menthol to participate in five experimental sessions. During the experimental session, subjects will be given an IV infusion of either saline or 1 mg nicotine at rapid, moderate or slow infusion rates (nicotine at 0.24,0.096, 0.048 and 0.024, mcg per kg body weight per sec). The infusion conditions for each experimental session will be determined in random order. Aim 1 is to establish a dose-effect curve for positive subjective effects (drug liking and good drug effects) and alleviation of smoking urges, as a function of nicotine delivery rate in menthol and non-menthol cigarette preferring smokers Aim 2 is to establish a dose-effect curve positive subjective effects and alleviation of smoking urges as a function of nicotine delivery rate. Aim 3 is to establish a dose-effect curve for nicotine's effect to alleviate symptoms of nicotine withdrawal in abstinent smokers as a function of nicotine delivery rate. Aim 4 is to establish a dose-effect curve for nicotine's acute cardiovascular health effects. Data from this project will help to establish benchmark values for nicotine's threshold effects that will guide policies on the nicotine yield of tobacco products. Presented is the time frame at which the peak change was strongest by treatment arm. The possible peak numbers could be 1, 3, 5, 7 and 10 minutes."

Inclusion criteria:

• Female and male smokers, aged 18 to 35 years, who have been smoking tobacco cigarettes for at least a year
• Smoke ≥ 5 and less than 20 cigarettes per day;
• Urine cotinine levels > 100 ng/mL consistent with nicotine intake of an active smoker (23)
• Not seeking treatment at the time of the study for nicotine dependence;
• In good health as verified by medical history, screening examination, and screening laboratory tests
• For women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods.

Exclusion criteria:

• History of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study
• Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
• Current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine
• Use of e-cigarettes more than 10 days in the past 30 days
• Urine drug screening indicating recent illicit drugs use (with the exception of marijuana).

Up to 10 minutes post-infusion.

Participant will not know nicotine dose or rate of infusion.