To examine the acute reinforcing effects of menthol, a fruit flavor (green apple) or a fruit flavor plus menthol, alone or in combination with nicotine in smokers. Flavors will be administered by inhalation via electronic cigarettes (e-cigarettes) and nicotine will be administered intravenously. The reinforcing drug effects will be measured with the drug effects questionnaire (DEQ).

This is a proposed double-blind, crossover study that enrolls young adult smokers who prefer menthol cigarettes. The study will consist of an adaptation session and three test sessions. In the adaptation session, participants will practice using the e-cigarette by sampling the flavors to be used in the test sessions. The test sessions will be performed following overnight abstinence from tobacco. Across the three test sessions, participants will be assigned to a random sequence of the three different e-cigarette conditions: menthol, green apple or menthol plus green apple, a different flavor condition for each test session. In each test session, just after the assigned flavor is delivered via the e-cigarette, participants will receive a random order of one intravenous delivery of saline, and two intravenous deliveries of nicotine (3.6 mcg/kg and 7 mcg/kg or 0.25 mg/70 kg and 0.5 mg/70kg), one hour apart. The test sessions will be performed at least 24 hours apart to minimize carryover nicotine effects. The main outcome measure will be subjective drug effects as measured with the Drug Effects Questionnaire (DEQ). Other outcomes include cardiovascular measures, cognitive performance, and self-report measures of nicotine withdrawal and craving. Cardiovascular measures include heart rate, systolic and diastolic blood pressure. Cognitive performance will be assessed with the Stroop test, mathematical processing test (MPT), and continuous performance test (CPT). Nicotine withdrawal measures will be measured with the Minnesota Nicotine Withdrawal Symptom Checklist (M-NWSC) and the Brief Questionnaire on Smoking Urges (BQSU).

Inclusion Criteria:

Female and male mentholated cigarette smokers, aged 18 to 30 years; history of smoking for the past 12 months, at least one cigarette per day; smoking status is verified with urinary cotinine levels above 10 ng/ml; not seeking treatment for nicotine dependence at the time of study entry 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 illnesses that the physician investigator deems as contraindicated for the patient to be in the study; regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics); psychiatric diagnosis and / or treatment for Axis I disorders including major depression, bipolar affective disorder, schizophrenia or panic disorder in the past month; abuse of alcohol or any other recreational or prescription drugs in the past 30 days; any allergy to propylene glycol or menthol; and 6) aversion to green apple flavor.

The SAFTEE is a technique for the systematic assessment of side effects in clinical trials developed by National Institute of Mental Health This was used before each Test Session and after each test session participants were observed no more than one month. There were no adverse events reported.

The SAFTEE is a technique for the systematic assessment of side effects in clinical trials developed by National Institute of Mental Health

The participant and medical professional will be blinded to the condition per day.