• Weight gain and smoking cessation
• Compliance with medication

• Alcohol consumption
• Tobacco and food craving
• Adverse events

This study will test a combination of the drugs naltrexone and bupropion with weight-concerned smokers to investigate whether or not this combination of drugs improves smoking cessation quit rates and minimizes post quit weight gain.

This is an open label smoking cessation clinical trial of 25 mg naltrexone with 300 mg bupropion sustained-release (SR) in six male and fourteen female participants. This pilot study is being conducted to determine:

• effect size estimates for smoking cessation and post-cessation weight gain, which will be used to compute the sample size needed for a large-scale clinical trial; and
• compliance with a combination of 25 mg naltrexone and 300 mg bupropion SR. In addition to examining the sample in this study, the investigators plan to compare this sample to a sample of matched controls.

• Smoking
• Nicotine Dependence

• Drug: Naltrexone
• Drug: Bupropion

Inclusion Criteria:

• Ages 18 and older
• Willingness and ability to give written consent
• Smoking at least 10 cigarettes per day for at least 1 year
• Baseline expired carbon-monoxide level of at least 10 ppm
• Weigh at least 100 lbs.
• English-speaking
• One person per household
• At least 1 prior quit attempt
• Concern about gaining weight. This will be assessed using a questionnaire that will provide a rating system to determine qualified participants.

Exclusion Criteria:

• Pregnant or nursing women or women attempting to conceive
• Serious current neurologic, psychiatric or medical illness, including unstable cardiac, hepatic, or renal disease and diabetes and hypertension
• Current alcohol dependence
• Current use of opiates, and/or a urine toxicology screen positive for opiates
• Chronic pain conditions necessitating opioid treatment (naltrexone, an opioid antagonist will make these medications ineffective)
• Evidence of significant hepatocellular injury as evidenced by AST or ALT >3 x normal or elevated bilirubin
• History of cirrhosis
• Body mass index (BMI) greater than 35
• History of anorexia nervosa or bulimia
• Current major depression
• Currently taking Toprol-XL (or metoprolol succinate)
• History of seizure disorder or serious brain injury
• Current use of smokeless tobacco, pipes, cigars, nicotine gum, nicotine patch, nicotine inhaler, nicotine lozenge, nicotine nasal spray, or bupropion
• Previous hypersensitivity to bupropion
• Patients requiring concomitant therapy with any psychotropic drug
• Participation in the Framing Messages for Smoking Cessation With Bupropion study (HIC#: 10880)