This study aims to determine if varenicline (Chantix®), currently used as a smoking cessation aid, will decrease the likelihood of relapse to smoking following a programmed lapse in the laboratory. The hypothesis is that varenicline will reduce the reinforcing effects of smoking and will delay or prevent relapse compared to placebo.

In this study, the investigators plan to use an experimental model of a lapse, in which volunteers smoke two cigarettes after a brief period of (12-24 hours). The goals of this study are to assess the impact of varenicline on the subjective and reinforcing effects of cigarettes, as well as the latency to resume smoking (relapse) following the lapse exposure.

Inclusion Criteria:

• Age 18-75 years old
• Reports smoking at least 10 cigarettes per day AND provides a urine sample that tests positive for nicotine metabolites at intake
• Contemplating a smoking cessation attempt in the near future
• Willing to engage in a practice quit attempt during which they will be asked to smoke on one occasion
• Able to give informed consent

Exclusion Criteria:

• Currently meets Diagnostic and Statistical Manual (DSM-IV) criteria for depression, bi-polar disorder, or schizophrenia
• History of attempted suicide or expresses any current suicidal ideation
• Pregnant, breast feeding, or planning to become pregnant within the next 3 months
• Reports desire for immediate treatment of tobacco/nicotine dependence
• Severe impairment of renal function indicated by Glomerular Filtration Rate (GFR) less than 30 ml/min calculated using the Cockcroft and Gault prediction method (plasma creatinine adjusted by weight, gender, and age)

4 weeks

Experimental model of relapse used in non-treatment seeking smokers. Results may not generalize to all smokers.