Effects of Flavors on Nicotine Reinforcement in Smokers
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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).
    

Detailed description: 
      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).
    

Intervention name(s): IV nicotine; Menthol flavor; green apple; green apple and menthol
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Subjects in each arm will receive three infusions in a random order one hour apart. The infusions will be saline, 0.25mg/70kg and 0.5mg/70kg; American e-liquids' menthol flavor used in e-cigarettes will be used as the placebo comparator; green apple will be added to the menthol flavor; menthol and green apple will be the active intervention
Other intervention name(s): nicotine, e-liquid; menthol American e-liquids; green apple American e-liquids; green apple and menthol flavor American e-liquids
Intervention MeSH terms: Menthol; Nicotine
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Mixed-effects models will be used to test the study hypotheses. These models allow for different numbers of observations per subject, use all available data on each subject, and are unaffected by randomly missing data.
Masking: Double (Participant, Investigator)
Primary purpose: Health Services Research