Nicotinic Hepatic Metabolism on Neuroreceptor Substrates of Nicotine Addiction

Inclusion criteria

• Participants will be 18-65 years of age
• Self-reported cigarette smoking history of at least 10 cigarettes/day for at least 6 months prior to enrollment
• Carbon monoxide reading > 10 ppm at the initial screening session
• Participants agree to be compliant with all study procedures including smoking abstinence and willingness to complete over-night stays at the Hospital of the University of Pennsylvania
• Participants must be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific procedures.

Exclusion criteria

• Women who are pregnant at the time of screening will not be eligible for this study. A urine pregnancy test will be performed in women of childbearing potential at screening.
• Self-reported regular (daily) use of chewing tobacco, snuff or snus
• Current enrollment in a smoking cessation or research program involving the use of nicotine substitutes
• History within one year or currently receiving treatment for substance abuse other than nicotine (e,g,, alcohol, opioids, cocaine, marijuana, or stimulants)
• Current use of cocaine, methamphetamines or other psychoactive substances per self-report and/or positive urine drug screen at the initial screening session
• Self-reported current alcohol consumption that exceeds greater than 25 drinks per week in men and 18 drinks per week in women
• BrAC reading greater than or equal to 0.01% at the initial screening session
• History of kidney and/or liver disease per medical record review or self-reported
• Uncontrolled hypertension (defined as Systolic BP > 160 and/or Diastolic BP > 100 at the screening intake session)
• History of Posttraumatic Stress Disorder (PTSD), bipolar disorder, schizophrenia or other psychotic disorder or Attention-Deficit/Hyperactivity Disorder (ADHD) as assessed by medical record review and/or self-report. History of unipolar depression or anxiety disorder may be accepted; current depression or anxiety may be accepted if the severity does not require psychoactive medication as assessed by medical record review and/or self-report.
• History of head trauma, that in the opinion of an investigator may interfere with the uptake of [18F]2-FA, as assessed by medical record review and/or self-report
• Current use or recent discontinuation (within the last 14 days) of any of the following:

• Smoking cessation medication (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix).
• Anti-psychotic medications.
• Certain medications used to treat depression, including SSRIs, Wellbutrin, MAOIs, and tricyclic antidepressants.
• Prescription stimulants (e.g. Provigil, Ritalin, Adderall).
• Current use of any of the following:

• Nicotine replacement therapy (NRT).
• 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).
• Any drug the investigator determines could interfere with scan results.
• Daily use of any of the following:

• 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 the Intake Session, the participant will be ineligible.
• Rescue Inhalers (e.g. Albuterol, Proventil, Ventolin, or Maxair).
• Any contraindication to brain MRI
• Any current medical condition, psychiatric disorder, illness, or disorder as assessed by medical record review and/or self-reported that is considered by a physician investigator to be a condition that could compromise participant safety or successful participation in the study