Effects of Varenicline on Brain Activity During Nicotine Abstinence

Inclusion Criteria: 1. Treatment-seeking smokers between the ages of 18 and 65, that smoke at least 10 cigarettes/day for at least the past 6 months 2. Provide a baseline CO (carbon monoxide) reading of \>10ppm 3. Provide written informed consent and are fluent, English-speaking 4. Weight of equal to or less than 300 lbs Exclusion Criteria: Smoking Behavior 1. Use of chewing tobacco, snuff or cigars 2. Current enrollment or plans to enroll in another smoking cessation program in the next 5 months 3. Plan to use other nicotine substitutes or smoking cessation treatments in the next 5 months 4. Provide a baseline CO (carbon monoxide) reading ≤10 ppm Alcohol/Drug Exclusion Criteria 1. History of substance abuse and/or currently receiving treatment for substance abuse 2. Current alcohol consumption that exceeds 25 standard drinks/week 3. A breath alcohol concentration reading ≥ 0.01 at the H\&P (health \& physical) screening or either of the lab sessions Medication Exclusion Criteria 1. Prior use of Chantix 2. Current use or recent discontinuation (within last 14-days) of the following medications: 1. Any form of smoking cessation medication 2. Any form of anti-psychotic medications that includes: * antipsychotics, * atypical antipsychotics, * mood-stabilizers, * anti-depressants (tricyclic, SSRI, MAOI), * anti-panic agents, * anti-obsessive agents, * anti-anxiety agents, and * stimulants (e.g., Provigil, Ritalin) * herbal medications (St. John's Wort) 3. Opioid medication for chronic pain 4. Anti-coagulants 5. Any heart medications 6. Daily medication for asthma Medical Exclusion Criteria 1. Women who are pregnant, planning a pregnancy, or lactating; 2. History or current diagnosis of psychosis, current major depression, bipolar disorder, ADHD, schizophrenia, or any Axis 1 disorder as identified by the MINI 3. Serious or unstable disease within the past 6 months (heart disease, HIV) 4. Diagnosis of cancer in the past 6 months or if successful treatment for cancer has not ended within the past 6 months 5. History of epilepsy or a seizure disorder 6. History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia (\>100 beats/minute); history or current diagnosis of COPD (chronic obstructive pulmonary disease), cardiovascular disease (stroke, angina, coronary heart disease), heart attack in the last 6 months, uncontrolled hypertension (SBP\>150 or DBP\>90) 7. History of kidney and/or liver failure (including transplant) 8. History of head trauma or prior seizure; family history of a seizure disorder, brain (or central nervous system) tumor 9. Use of pacemakers, certain metallic implants, or presence of metal in the eye as contraindicated for MRI (magnetic resonance imaging); 10. Low or borderline intellectual functioning - determined by receiving a score \<80 on the Shipley verbal IQ Test 11. Non-English speaking; determined at phone screen 12. History of claustrophobia (contraindicated for MRI) or color blindness (task requires color recognition); self-report at telephone screen 13. Being left-handed 14. Any fore-limb deformity 15. Wearing cochlear implant or bi-lateral hearing aids General Exclusion 1. Any medical condition 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. 3. Any physical or visual impairment that may prevent the individual from using a computer keyboard or completing any study tasks.