Nicotine's Potential Abuse With Menthol

To examine if switching from menthol to non-menthol cigarettes will change the dose-effect curves for positive subjective effects and alleviation of smoking urges as a function of nicotine delivery rate in smokers.

A placebo-controlled study that will recruit male and female menthol nicotine dependent smokers. Following screening and evaluation as described above, eligible participants will be enrolled in the study which will last about 4 weeks. Eligible, participants will be randomized to menthol or non-menthol smoking condition for 2 weeks (Phase 1) and then will be switched to the alternative condition for another 2 weeks (Phase 2). The smoking condition will be open label. Participants will be provided with free cigarettes in Phases 1 and 2. For the menthol condition, participants will be provided their usual brand of menthol cigarettes and for the non-menthol condition, they will be provided a matched-brand non-menthol cigarette (e.g., Newport Non-Menthol Gold 100s for those who smoke Newport Menthol Gold 100s). In week 2 of each Phase, participants will have a test session. Each session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes. Once the participants complete the test session, participants will be crossed-over to the alternative treatment. The period between the 2 Phases will not be longer than one week.

subjects will be unblinded to smoking menthol or non menthol for two weeks before each test session. Each session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes. Once the participants complete the test session, participants will be crossed-over to the alternative treatment.

session will include 3 infusions in the same order: nicotine (1 mg per 70 kg body weight) delivered over 5 minutes, saline and nicotine (1 mg/ 70 kg) delivered over 2.5 minutes.

To explore the dose-effect curves of nicotine delivery rate for a) reinforcement (assessed with the Multiple-Choice Questionnaire), b) heart rate and blood pressure, and c) tobacco withdrawal severity, assessed with self-report symptoms and cognitive performance.

The SAFTEE is a technique for the systematic assessment of side effects in clinical trials developed by National Institute of Mental Health (Levine & Schooler, 1986). It is a questionnaire that rates the current severity of a wide range of somatic, behavioral and affective symptoms in general and specific inquiry formats. It is designed to report adverse health events, regardless of whether or not they are suspected to be drug related, in order to reduce the under-reporting of unanticipated events compared with "known or expected" events.

Inclusion Criteria: 1) Female and male smokers, aged 21 to 35 years, who have been smoking tobacco cigarettes for at least a year; 2) smoke ≥ 5 and less than 20 cigarettes per day; 3) urine cotinine levels > 100 ng/mL consistent with nicotine intake of an active smoker 4) not seeking treatment at the time of the study for nicotine dependence; 5) in good health as verified by medical history, screening examination, and screening laboratory tests; 6) for women, not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods. Exclusion Criteria: 1) history of major medical or psychiatric disorders that the physician investigator deems as contraindicated for the subject to be in the study; 2) regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics); 3) current alcohol or substance dependence for any other recreational or prescription drugs other than nicotine; 4) use of e-cigarettes more than 10 days in the past 30 days; 5) urine drug screening indicating recent illicit drugs use (with the exception of marijuana).