Role of Metabolites in Nicotine Dependence (1) - 1

The purpose of this study was to determine the effects of a metabolite of nicotine,
cotinine, on tobacco withdrawal symptoms. Cotinine has been shown to have psychoactive
effects that are similar as well as different from those of nicotine, however, little
research has been conducted examining the role cotinine plays in nicotine addiction. This
study compared the effects of cotinine with the nicotine patch, and a combination thereof on
tobacco withdrawal symptoms. The results showed that cotinine antagonizes the beneficial
effects of the nicotine patch in reducing withdrawal symptoms.

Inclusion Criteria:

Male or female subjects, aged 21-45 yrs inclusive, with a smoking history of at least 1
pack of cigarettes daily for at least 1 year. Subject must be in good health as verified
by medical history, screening exam, and screening laboratory tests. Subject must provide
written informed consent to participate in the study and be motivated to stop smoking for
a short term.

Exclusion Criteria:

History of myocardial infarction, angina pectoris, sustained or episodic cardiac
arrhythmias, symptomatic peripheral vascular disease, peptic ulcer disease or any other
medical condition which the physician or investigator deems inappropriate for
participation, insulin-dependent diabetes; pregnant or lactating or not using adequate
birth control methods; requirement of any form of regular psychotropic medication
(antidepressants, antipsychotics, or anxiolytics) and recent psychiatric history; chronic
use of systemic steroids or antihistamines; skin sensitivity which would preclude use of a
transdermal system; abuse of alcohol or any other recreational or prescription drug; use
of any other tobacco products, including smokeless tobacco and nicotine products; previous
use of transdermal nicotine system; inability to fulfill all scheduled visits and
examination procedures throughout the study period.