Pharmacogenetics of Nicotine Addiction Treatment

Inclusion Criteria: Eligible participants will be males and females 1. Between the ages of 18-65. 2. Smoke at least 10 cigarettes/day for the past 6 months. 3. Provide a baseline Carbon Monoxide (CO) reading greater than 10ppm at the Intake Session. 4. Are seeking smoking cessation treatment. 5. Plan to live in the area for the next 12 months. 6. Fluent English speaker. 7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and Health Insurance Portability and Accountability Act (HIPAA) form. All subjects must consent to use a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-Provera injection, contraceptive patch, tubal ligation) or abstain from sexual intercourse during the time they are taking study medication (pills and patches) and for at least one month after the medication period ends. All female subjects of child-bearing potential should not be pregnant for the duration of the study. Exclusion Criteria: Smoking Behavior 1. Regular (daily) use of chewing tobacco, snuff or snus. 2. Current enrollment or plans to enroll in another smoking cessation or research program in the next 12 months. 3. Plan to use other nicotine substitutes or smoking cessation treatments in the next 12 months. 4. Provide a baseline CO reading less than or equal to 10ppm at the Intake Session. Alcohol/Drug Exclusion Criteria 1. History (within the last year) or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants), excluding nicotine. 2. Current use of cocaine and/or methamphetamines (urine drug screen at the Intake Session). 3. Current alcohol consumption that exceeds greater than 25 standard drinks/week. 4. Current alcohol abuse or dependence. 5. Current non-alcoholic psychoactive substance abuse or dependence. Medical Exclusion Criteria 1. Women who are pregnant, planning a pregnancy, or lactating. 2. History of epilepsy or a seizure disorder. 3. Current medical problems for which transdermal nicotine is contraindicated including: * Allergy to latex. * History of kidney and/or liver disease, including transplant (self-report). * Uncontrolled hypertension (determined as a Systolic Blood pressure (SBP) reading greater than 160 and/or a Diastolic Blood Pressure (DBP) greater than 100). 4. Serious or unstable disease within the past 6 months. 5. History (last 6 months) of abnormal heart rhythms, tachycardia and cardiovascular disease (stroke, angina, heart attack) may result in ineligibility. These conditions will be evaluated on a case by case basis by the Study Physician. 6. Inability to provide a blood sample to be used to assess nicotine metabolite ratio. Psychiatric Exclusion Criteria (as determined by self report \& MINI) 1. Current diagnosis of major depression. Persons with a history of major depression, if stable for 6 months or longer, are eligible, provided they are not excluded based on medications (below). 2. Any suicide risk score on MINI or self-reported suicide attempt on telephone screen. 3. Current or past hypomanic/manic episode. 4. History or current diagnosis of Post Traumatic Stress Disorder (PTSD). 5. History or current diagnosis of psychotic disorder, bipolar disorder, schizophrenia. Medication Exclusion Criteria 1. Current use or recent discontinuation (within the last 14-days) of: * Smoking cessation medication (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix); NOTE: Once participants are found eligible for the study, they are instructed to use the smoking cessation medication provided to them by the study staff. If a subject reports an isolated (non-daily) instance of using a non-study smoking cessation medication, the study physician and PI will evaluate the situation and determine if it is safe for the subject to continue participation. * Anti-psychotic medications. * Certain medications used to treat depression, including Wellbutrin, Monoamine Oxidase Inhibitors (MAOIs), and tricyclic antidepressants. * Prescription stimulants (e.g. Provigil, Ritalin, Adderall). 2. Current use of: * Nicotine replacement therapy (NRT); NOTE: Once participants are found eligible for the study, they are told they should only use the NRT provided to them by the study staff. If a subject reports an isolated (non-daily) instance of NRT use during the study, they may be permitted to continue. * Tagamet (cimetidine). * Heart medications such as digoxin, quinidine, nitroglycerin; use of these medications may result in ineligibility and will therefore be evaluated on a case-by-case basis by the Study Physician. * Anti-coagulants (e.g., Coumadin, Warfarin). 3. Daily use of: * Opiate-containing medications for chronic pain; if a participant reports taking an opiate-containing medication every day for the 14 days prior to the telephone screen and/or Intake Session, the participant will be ineligible. * Rescue Inhalers (e.g. albuterol, proventil, ventolin, or maxair) General Exclusion 1. Any medical condition, illness, disorder or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator and/or Study Physician. 2. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.