The purpose of this study is to compare the effects of bupropion + placebo to bupropion + naltrexone as treatments to help smokers quit.

The purpose of this study is to compare the effects of bupropion + placebo to bupropion + naltrexone as treatments to help smokers quit. Bupropion is an FDA-approved medication for smoking cessation that is believed to provide relief from craving and withdrawal through promotion of two neurotransmitter chemicals, dopamine and noradrenaline. Naltrexone is an FDA-approved medication for the treatment of opiate and alcohol dependence, that appears to function through blocking certain opiate receptors in the brain. It is expected that bupropion + naltrexone will produce higher smoking quit rates than bupropion + placebo. Bupropion alone is effective in alleviating some nicotine withdrawal complaints and craving for nicotine. However, bupropion does not reduce the rewarding effects of slips to smoking. Naltrexone alone is not generally effective as a smoking cessation medication, but it does help to reduce the rewarding effects of slips to smoking. Thus, it may help to prevent full relapse to smoking. In addition, naltrexone can help to reduce craving for cigarettes. It is hypothesized that the differing complementary actions of the two drugs will help smokers more than bupropion alone. In addition to examining smoking quit rates, the proposed study will also look at psychological processes that change during smoking cessation including, nicotine withdrawal, nicotine craving, mood, impulsivity, and attention

Inclusion Criteria:

• 18 years and older.
• Smoked at least 10 cigarettes/day for at least 1 year.
• English speaking.
• Females who are of childbearing potential must practice effective contraception and meet the following criteria:
• Are instructed to avoid pregnancy through 30 days after the last dose of study medication.
• Have a negative urine pregnancy test at baseline.
• Agree to use of the birth control methods listed: an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g., Norplant), or an injectable contraceptive (e.g., Depo-Provera) for at least one month prior to entering the study and will continue its use through at least 30 days after the last dose of the study medication. A barrier method of contraception (e.g., condom or diaphragm with spermicide) while participating in the study and 30 days after the last dose of study medication.
• Willingness to reduce alcohol consumption during study to 2 or fewer standard drinks/day (3 oz. of alcohol or two beers (12 oz.), or two 5 oz. glasses of wine).
• Willingness to not use illicit drugs during study period including marijuana.

Exclusion Criteria:

• Concurrent use of tobacco products (other than cigarettes) or nicotine products.
• Contraindications to use of bupropion (i.e., concurrent use of other forms of bupropion, MAO inhibitors, anti-depressant medication, seizure disorder or any clinical situation that might increase risk for seizures, past head injury, current or prior diagnosis of bulimia or anorexia nervosa; bipolar disorder).
• Contraindications to use of naltrexone (i.e., past history of opioid abuse or dependence or evidence of opioid use in the past 30 days; significant hepatocellular injury as evidenced by liver enzyme levels over 3 times normal limits).
• Use of medications whose metabolism or effects may be adversely altered by bupropion or naltrexone. Medications that contraindicate the use of bupropion include theophylline, procarbazine, carbimazole, nialamide, pargyline, toloxatone, iproniazid, and systemic steroids. Medications that contraindicate the use of naltrexone include opioid analgesics and yohimbine.
• Current use of anti-seizure medications, disulfiram, or any medications that significantly challenge liver functioning.
• Treatment for drug or alcohol dependence during the last year, or evidence of alcohol abuse so severe that the patient is judged potentially unable to comply with the protocol.
• Evidence of problem alcohol consumption based on AUDIT.
• Self-reported use of illicit drugs in the past 90 days (including opioids, but excluding marijuana).
• Suicidal or homicidal ideation.
• Current major depression.
• History of bipolar disorder.
• Recent (within twelve months) myocardial infarction.
• Pregnant or lactating or planning pregnancy during treatment period.
• Having plans to leave the immediate geographical area within 9 months.
• Unwillingness or inability to given written informed consent.