The Effects of Menthol as Delivered by an Electronic Cigarette on the Desirability of Nicotine in Tobacco Users
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional

Summary: 
      This study will help determine if menthol administered by inhalation via electronic
      cigarettes (e-cigarette) changes the reinforcing effects of pure nicotine administered
      intravenously in cigarette smokers who smoke mentholated or non-mentholated cigarettes.
    

Detailed description: 
      Male and female smokers will be recruited from the New Haven area through newspaper
      advertisements, radio advertisements, and fliers. Interested subjects will have the study
      described over the telephone, and they will be asked to answer a brief tobacco use history
      and medical screening questionnaire. If subjects pass the telephone screening, they will be
      invited to come to the West Haven VA clinic for a screening evaluation. This screening
      evaluation will be for the menthol / nicotine reinforcement study as described in detail in
      this project description. The dose-finding study was conducted at the John B. Pierce
      Laboratory. The dose finding study concluded with the establishment of the high and low dose
      of menthol that will be used in this protocol "Menthol's Effects on Nicotine Reinforcement in
      Smokers." The screening of these subjects used the same inclusion and exclusion criteria as
      described below.

      Inclusion criteria: Female and male 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 and abuse of alcohol or any other recreational or
      prescription drugs in the past 30 days. Any allergy to propylene glycol or menthol.

      This outpatient, double-blind, placebo-controlled study consisted of an adaptation session
      followed by three test sessions. All participants were randomized to a test session order and
      received control menthol (0.0% + tobacco flavor), low menthol (0.5% + tobacco flavor), and
      high menthol (3.2% + tobacco flavor) by standardized inhalation from an e-cigarette just
      prior to each nicotine infusion (a single menthol condition for each test session). Within
      each test session, all 3 IV nicotine conditions were tested, one hour apart, by delivering
      saline, nicotine at 0.25 mg nicotine/70 kg and nicotine at 0.5 mg nicotine/70 kg, in a random
      order, just after last inhalation. For each participant, the randomized nicotine infusion
      sequence was fixed across the three test sessions, each performed at least 24 hours apart.
    

Intervention name(s): nicotine; menthol
Intervention type(s): Drug; Drug
Intervention description(s): In each of 3 test sessions, subjects in each arm will receive a randomized sequence of three intravenous infusions (30 sec each), one hour apart. The infusions will consist of saline, nicotine (.25 mg / 70kg) and nicotine (0.5 mg / 70 kg). The randomized sequence will remain the same between test sessions for a given subject.; In each of 3 test sessions, subjects will take 6 inhalations from the study e-cigarette, one inhalation every 15 seconds, of the randomized menthol condition for that test session ust prior to each intravenous infusion. The menthol conditions are: 3.2% menthol, 0.5% menthol and tobacco-flavor only (0.0% menthol)
Other intervention name(s): racemic menthol
Intervention MeSH terms: Menthol; Nicotine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects in each of the 2 arms received a random sequence of 3 different inhaled menthol conditions across 3 test sessions (a single menthol condition for each test session). In each test session, a random order of one saline, and 2 nicotine (0.25 mg and 0.5 mg /70 kg) infusions were given one hour apart, concurrent with the randomized menthol inhalation condition for that test session. The randomized sequence of nicotine infusions was the same for each test session.
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: menthol, electronic cigarette, nicotine, smoking, tobacco