Effects of Flavors on Nicotine Reinforcement in Smokers

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.