Varenicline or Nicotine Patch and Nicotine Gum in Helping Smokers in a Methadone Treatment Program Stop Smoking

OBJECTIVES: Primary * To determine whether varenicline, a nicotine receptor partial agonist, leads to a higher rate of smoking cessation than combination nicotine replacement therapy with nicotine patch prescription plus ad libitum nicotine gum delivery in methadone-maintained smokers. Secondary * To test the effects of the treatments on smoking urges, withdrawal symptoms, and reinforcing effects of smoking. * To test the effects of the treatments on methadone treatment outcomes, including retention in methadone maintenance, methadone dose changes, and continued use of illicit drugs as measured by urine toxicologies. OUTLINE: This is a multicenter study. Patients are stratified based on gender and level of nicotine dependence. Patients are randomized to 1 of 3 intervention arms. At baseline, all patients receive a minimal behavioral intervention using a 3-minute, simple smoking cessation counseling strategy, a self-help manual, and a telephone quit-line number. * Arm I (varenicline): Patients receive oral varenicline once daily on days 1-3 and twice daily thereafter for a total of 6 months or when a comfortable level of smoking abstinence is reached. * Arm II (placebo): Patients receive oral varenicline placebo once daily on days 1-3 and twice daily thereafter for a total of 6 months or when a comfortable level of smoking abstinence is reached. * Arm III (nicotine patch/gum): Patients receive a nicotine patch, with doses tapering over time for a total of 26 weeks. Patients also receive nicotine gum to quell breakthrough urges. Patients may stop treatment when a comfortable level of smoking abstinence is reached. Patients complete a brief interview over 10-15 minutes at 2 weeks and monthly during months 1-5. They complete a longer interview over 45 minutes at months 6 and 12 and provide breath samples (for carbon monoxide monitoring) and urine samples (for cotinine testing). NOTE: Smoking cessation may prevent certain smoking-related illnesses, including cancer. PROJECTED ACCRUAL: A total of 602 patients (258 receiving varenicline, 258 receiving nicotine replacement therapy, and 86 receiving placebo) will be accrued for this study.