Effects of Varenicline on Cigarette Self Administration
Condition: Nicotine Dependence
MeSH terms: Tobacco Use Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      The investigators hypothesize that varenicline will dose dependently attenuate the subjective
      effects of cigarettes after a period of abstinence. Also, treatment with varenicline will
      dose dependently weaken the severity of nicotine withdrawal symptoms. Thirdly, we hypothesize
      that treatment with varenicline will dose dependently decrease cigarette self-administration
      in the model proposed.
    

Detailed description: 
      Tobacco use is the leading preventable cause of death in the U.S.A. Every year 400,000 people
      die from cigarette smoking and in 2006, one out of every five deaths in the US were smoking
      related. Recent advances in laboratory studies of tobacco effects in humans and in
      understanding the effects of nicotine on the brain and behavior present an opportunity to
      advance medication development.

      The addictive properties of nicotine are thought to be a result of nicotine triggering the
      acute release of dopamine, a pleasurable event that a person seeks to repeat. Varenicline is
      a partial agonist of the nicotine receptors, therefore also triggering the release of
      dopamine but in a more sustained and moderate manner, which could counter the low dopamine
      levels arising from a lack of nicotine and therefore aid craving. Also, by binding to these
      nicotine receptors in advance of smoking, it could stop nicotine from binding and creating
      pleasurable effects.

      This study will assess the effect of acute treatment with varenicline and placebo on early
      tobacco withdrawal, acute effects of cigarettes and cigarette self-administration in
      cigarette-smoking volunteers. After overnight abstinence, participants will come into the lab
      and receive acute treatment with varying doses of varenicline or placebo and perform computer
      tests and fill out questionnaires. Then they will be given the opportunity to smoke under
      operational conditions (cigarette versus money choice). This study will employ a
      within-group, double-blind, randomized and counterbalanced design.

      The main goal of this project is to improve the current laboratory model of smoking cessation
      and study the mechanism involved in smoking maintenance. We hypothesize that varenicline will
      dose-dependently: 1) decrease nicotine withdrawal symptoms, 2) decrease acute effects of
      cigarettes and 3) decrease self-administration of cigarettes in the laboratory paradigm.
      Showing the effectiveness of varenicline in the proposed laboratory model will confirm the
      model's predictive validity to detect clinically effective medication.
    

Intervention name(s): Varenicline; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 4 doses of Varenicline. 1 capsule of either dose (0mg, 0.5mg, 1mg, 2 mg) in the morning on days at least 5 days apart.; 1 dose of placebo
Other intervention name(s): Chantix
Intervention MeSH terms: Varenicline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment