Nicotinic Hepatic Metabolism on Neuroreceptor Substrates of Nicotine Addiction

Inclusion Criteria:

1. Participants will be 18-65 years of age

2. Self-reported cigarette smoking history of at least 10 cigarettes/day for at least 6
months prior to enrollment

3. Carbon monoxide reading > 10 ppm at the initial screening session

4. 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

5. 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:

1. 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.

2. Self-reported regular (daily) use of chewing tobacco, snuff or snus

3. Current enrollment in a smoking cessation or research program involving the use of
nicotine substitutes

4. History within one year or currently receiving treatment for substance abuse other
than nicotine (e,g,, alcohol, opioids, cocaine, marijuana, or stimulants)

5. Current use of cocaine, methamphetamines or other psychoactive substances per
self-report and/or positive urine drug screen at the initial screening session

6. Self-reported current alcohol consumption that exceeds greater than 25 drinks per week
in men and 18 drinks per week in women

7. BrAC reading greater than or equal to 0.01% at the initial screening session

8. History of kidney and/or liver disease per medical record review or self-reported

9. Uncontrolled hypertension (defined as Systolic BP > 160 and/or Diastolic BP > 100 at
the screening intake session)

10. 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.

11. 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

12. Current use or recent discontinuation (within the last 14 days) of any of the
following:

1. Smoking cessation medication (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix).

2. Anti-psychotic medications.

3. Certain medications used to treat depression, including SSRIs, Wellbutrin, MAOIs,
and tricyclic antidepressants.

4. Prescription stimulants (e.g. Provigil, Ritalin, Adderall).

13. Current use of any of the following:

1. Nicotine replacement therapy (NRT).

2. Tagamet (cimetidine).

3. 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.

4. Anti-coagulants (e.g. Coumadin, Warfarin).

14. Daily use of any of the following:

1. 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.

2. Rescue Inhalers (e.g. Albuterol, Proventil, Ventolin, or Maxair).

15. Any contraindication to brain MRI

16. 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