Varenicline and Nicotine Interactions in Humans (VA)

This will be a 2-4 week double-blind, placebo-controlled study. Twenty four male and female smokers will have two 4-day treatment periods, in which they will be randomized to varenicline (1 mg/day) or placebo. During the first 3 days of each treatment period, smokers will have daily clinic visits and receive their study medication. On Day 4, subjects will come to the laboratory, where they will receive ascending doses of intravenous (IV) nicotine (0.1, 0.4, and 0.7 mg per 70kg). This procedure will allow accurate assessment of varenicline effects on the subjective, physiological and cognitive responses to nicotine. Following a washout period, subjects will be crossed over to the alternative treatment.

Inclusion criteria

• Female and male smokers, aged 18 to 55 years
• History of smoking daily for the past 12 months, at least 15 cigarettes daily
• Carbon Monoxide (Alveolar) level > 10ppm
• For women: not pregnant as determined by pregnancy screening, nor breast feeding, and using acceptable birth control methods

Exclusion criteria

• History of heart disease, renal or hepatic diseases
• other medical conditions that the physician investigator deems as contraindicated for the subject to be in the study
• Regular use of psychotropic medication (antidepressants, antipsychotics, or anxiolytics)
• recent psychiatric diagnosis and treatment for Axis I disorders including
• major depression, bipolar affective disorder,
• schizophrenia and panic disorder within the past year
• Current dependence on alcohol
• drugs or treatments for drug
• alcohol addiction within the past 5 years
• Allergy to varenicline