Nicotine Withdrawal Symptoms and Smoking Relapse

• INCLUSION CRITERIA:

All participants must:

1. Be between the ages of 18-55. Be right-handed.
2. Be in good health.
3. Be free of active DSM-IV dependence, or dependence in partial remission, on alcohol or any drug except nicotine. Past active dependence is acceptable provided it is at least five years in the past and total time of active dependence did not exceed 4 years. Those with past dependence may not have any current use (past 6 months) of the substance on which they were dependent. While recreational/intermittent use of alcohol and/or marijuana will be tolerated in all participant groups, individuals will be excluded if they meet current or recent (within 5 years) DSM-IV diagnostic criteria for dependence on any substances. A positive drug test for marijuana will not be exclusionary as long as participants have not used in the 24hrs preceding the imaging visits. In the event of a positive drug test for marijuana, self-reports of current marijuana use will be used to differentiate intermittent/infrequent from chronic/frequent users. Given a possible link between marijuana use and psychosis frequent users, defined as those using twice or more per week within the last month, will be excluded from participation.
4. Be able to abstain from alcohol 24hrs before each of the imaging sessions and able to moderate their caffeine intake 12hrs before each session.
5. Be smoking, in general of 10cpd for the last two years and continuously for at least the last month prior to coming into screening.
6. Be actively seeking treatment for smoking cessation and willing to engage in 12-weeks of treatment involving daily administration of Varenicline and weekly counseling sessions, as well as follow-up assessments at 1, 6 and 12 months following treatment onset.
7. Be able to abstain from smoking for 36hrs on two occasions during the study.

EXCLUSION CRITERIA:

Participants will be excluded if they:

1. are not suitable to undergo an fMRI experiment due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia.
2. have coagulopathies, history of, current superficial, or deep vein thrombosis, musculoskeletal abnormalities restricting an individual's ability to lie flat for extended periods of time.
3. have HIV or Syphilis.
4. regularly use any prescription (e.g., antidepressants, benzodiazepines, antipsychotics, anticonvulsants, barbiturates), over-the-counter (e.g., cold medicine) or herbal medication (e.g., Kava, Gingko biloba, St. John's wort) that may alter CNS function, cardiovascular function, or neuronal-vascular coupling.
5. have any current neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis, multiple sclerosis, movement disorders, history of significant head trauma, or CNS tumor.
6. Have any current major psychiatric disorders to include, but not limited to, mood, anxiety, psychotic disorders, or substance-induced psychiatric disorders.
7. are cognitively impaired or learning disabled.
8. have significant cardiovascular or cerebrovascular conditions.
9. have moderate to severe renal impairment
10. are diabetic

11. have any other major medical condition that in the view of the investigators would compromise the safety of an individual during participation. The following lab values will result in exclusion from the study:

    i. Hemoglobin < 10 g/dl

    ii. White Blood Cell Count < 2400/micro

    iii. Liver Function Tests > 3 times normal

    iv. Serum glucose > 200 mg/dl

    v. Urine protein > 2 plus

    vi. Serum creatinine > 2 mg/dl

    vii. Estimated creatinine clearance < 60ml/min

    a. The MAI will retain discretion to exclude based on less extreme lab results. After the screening process has been completed, the MAI will take into account all data collected in order to decide if there is an existing medical illness that would compromise participation in this research.

12. pregnant, planning to become pregnant, or breastfeeding. Females are instructed in the consent to use effective forms of birth control during the study period. Urine pregnancy tests will be conducted at the beginning of each imaging visit.