The Effects of Menthol as Delivered by an Electronic Cigarette on the Desirability of Nicotine in Tobacco Users

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.

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);

- A 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.