Neural Mechanisms Associated With Risk of Smoking Relapse

Smoking is the greatest preventable cause of mortality and a significant economic burden.
Even with the best available treatments, most smokers relapse within days or weeks after a
quit attempt. Nicotine replacement therapy, the most widely used pharmacotherapy, yields end
of treatment quit rates of <25% suggesting that managing nicotine withdrawal is not
sufficient. To improve quit rates significantly, a more refined mechanistic understanding is
needed. Neuroimaging can identify mechanisms underlying behavior change beyond self-report
and behavioral measures. Functional magnetic resonance imaging (fMRI) studies show that brief
(e.g., 24 hr.) abstinence from smoking produces working memory deficits associated with
reduced neural activity in cognitive control circuits and weakened resting state functional
connectivity. Neural reactivity to smoking cues also increases risk of relapse, and
psychological stress can enhance neural responses to smoking cues and increase smoking
intensity. This study will examine how abstinence-induced brain changes contribute to
clinical outcomes in treatment-seeking smokers. Using a validated fMRI abstinence challenge
paradigm, 200 treatment-seeking smokers will complete two 1-hour pre-treatment fMRI scans:
after smoking satiety and after 24 hours of confirmed abstinence. The investigators will
examine brain responses during performance of tasks probing working memory, cue reactivity,
and stress response as well as resting state functional connectivity. Participants will then
set a target quit date, receive smoking cessation counseling, and be monitored for 6 months
to assess time to relapse using a validated smoking relapse protocol.

Inclusion Criteria:

Eligible participants will be:

1. Treatment-seeking smokers between the ages of 18 and 65, reporting consumption of at
least 5 cigarettes per day for at least the past 6 months;

2. Planning to live in the area for at least the next 3 months;

3. Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the combined consent and HIPAA form;

4. Able to communicate fluently in English (speaking, writing, and reading).

Exclusion Criteria:

Subjects who present and/or self-report with the following criteria at any point during
study participation will not be eligible to participate in the study:

Smoking Behavior:

1. Use of chewing tobacco or snuff or cigars;

2. Current enrollment or plans to enroll in another smoking cessation program or research
study in the next 3 months;

3. Current or anticipated (within the next 3 months) use of smoking cessation medications
or nicotine replacement therapy (NRT);

4. A baseline carbon monoxide (CO) reading less than or equal to 8ppm.

Alcohol/Drugs:

1. Diagnosis or treatment for alcohol or drug abuse in the past two years as reported
during phone screen (e.g., alcohol, opioids, cocaine, or stimulants);

2. Current alcohol consumption that exceeds 25 standard drinks/week;

3. Positive breath alcohol concentration test (BrAC greater than or equal to 0.01) at
intake;

a. Participants testing positive for breath alcohol with a reading equal to or greater
than .08 (the legal driving limit) or who are visibly impaired will be instructed not
to drive themselves home after the appointment. If a participant needs to use a phone
to call for a safe ride home, an office telephone will be made available to the
participant.

4. A positive urine drug screen for cocaine, opiates, PCP, benzodiazepines, methadone,
MDMA, amphetamine, methamphetamine, tri-cyclic antidepressants and/or barbiturates at
any session;

Medication:

Current use or recent discontinuation (within the past 30 days at the time of Intake) of:

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

2. Anti-psychotic medications;

3. Anti-depressants (tricyclics, SSRI's, selective and nonselective MAOIs,
Wellbutrin/Zyban);

4. Anti-anxiety agents;

5. Anti-panic agents;

6. Prescription (e.g., Provigil, Ritalin) or over-the-counter stimulants;

7. Prescription sleep aids (e.g., Ambien, Lunesta) if used more than 2x/week. If
participants report use less than twice a week, they will just be asked to refrain
from use during imaging portion of the study.

8. Any medication that could compromise participant safety as determined by the Principal
Investigator and/or Study Physician;

Daily use of:

9. Opiate-containing medications for chronic pain.

Medical/Neuropsychiatric:

1. Women who are pregnant, planning a pregnancy, and/or breast feeding. All female
subjects of childbearing potential will undergo a urine pregnancy test at Intake and
both fMRI scan visits (3 urine pregnancy tests in total).

2. History of epilepsy or a seizure disorder;

3. History of stroke;

4. Self-reported brain or spinal tumor;

5. Self-reported history or current diagnosis of psychosis, bipolar disorder,
schizophrenia, current major depression (subjects with a history of major depression
but in remission for past 6 months are eligible), or any Axis 1 disorder.

fMRI-Related:

1. Self-reported history of head trauma;

2. Self-reported brain (or CNS) or spinal tumor;

3. Self-reported use of pacemakers, certain metallic implants, or presence of metal in
the eye as contraindicated for fMRI;

4. Self-reported history of claustrophobia;

5. Being left-handed;

6. Color blindness;

7. Weight greater than 299lbs;

8. Self-reported history of gunshot wounds;

9. Any impairment preventing participants from using the response pad necessary for the
cognitive testing;

10. Circumstances or conditions that may interfere with magnetic resonance imaging (MRI).

General Exclusion:

1. Any medical condition, illness, disorder, or concomitant medication that could
compromise participant safety or treatment, as determined by the Principal
Investigator;

2. Low or borderline intellectual functioning - determined by a score of less than 85 on
the Shipley Institute of Living Scale (SILS) (administered at Intake Visit);

3. Enrollment or plans to enroll in another research study;

4. Inability to provide informed consent or complete any of the study tasks as determined
by the Principal Investigator.