Pharmacogenetics, Emotional Reactivity and Smoking

Inclusion Criteria

• Age: 18-65 years old
• Smoking: >/= 5 cigarettes per day within the 2 months preceding the screening visit and expired CO greater than or equal to 6 ppm.
• Able to follow verbal and written instructions in English and complete all aspects of the study
• Have an address and home telephone number where they may be reached
• Provide informed consent and agree to all assessments and study procedures
• Be the only participant in their household

Exclusion Criteria

• Within the month immediately preceding the screening visit; use of any form of tobacco product other than cigarettes on 3 or more days within a week only if the individual refuses to refrain from non-cigarette tobacco use during the course of this study
• Within the month immediately preceding the screening visit; use of marijuana in any form on 3 or more days within a week
• Within the two weeks immediately preceding the screening visit, involvement on more than 3 days in any formal smoking cessation activities
• Current visual or auditory problems that in the opinion of the investigator would interfere with the completion of study assessments
• Treatment on a continuous basis within 2 weeks before the screening visit: any contraindicated medication for Varenicline or Bupropion.
• Uncontrolled hypertension or other major contraindications for Bupropion or Varenicline.
• Severe renal impairment (CR Clearance <30 ml/min/1.73 m2).
• Laboratory evaluations outside normal limits and of potential clinical significance in the opinion of the investigator
• Meet current criteria for psychiatric disorders or substance abuse as assessed by the MINI for items A, B, D, I, J, K, L, M and N, including a past manic or hypomanic episode as well as a lifetime psychotic disorder.
• Subject rated as moderate to high on suicidality as assessed by the MINI.
• Psychiatric hospitalization within 1 year of screening date.
• A positive urine pregnancy test during the screening period. Women who are two years post menopausal, one year post-tubal ligation, or who have had a partial or full hysterectomy will not be subject to a urine pregnancy test.
• Pregnant, breast-feeding, or of childbearing potential who is not protected by a medically acceptable, effective method of birth control while enrolled in the study
• Use of Varenicline or Bupropion within two weeks before the screening visit.
• History of hypersensitivity or allergic reaction to Varenicline, tricyclic antidepressant, Bupropion (Wellbutrin, Zyban) or similar chemical classes or any component of these formulations.
• Subject considered by the investigator as unsuitable candidate for receipt of an investigational drug, or unstable to be followed up throughout the entire duration of the study.