Impact of Varenicline on Blood-Oxygen-Level Dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Activation on Smokers

Treatment with varenicline reduces overall subjective cigarette craving and smoking reward in
nicotine-dependent smokers. This preliminary study will explore the impact of varenicline
treatment on smoking cue-induced craving and associated regional brain activation using BOLD
fMRI. Twenty healthy smokers (10 males, 10 females) will undergo two BOLD fMRI scans with the
presentation of smoking-related and neutral cues at baseline and after five weeks of
treatment with open-label varenicline. The investigators hypothesize that participants will
report reduced urges to smoke on the Questionnaire of Smoking Urges-Brief and have less
activation of the brain areas associated with craving during the fMRI after 5 weeks of
varenicline and smoking cessation counseling compared to the baseline scan.

Inclusion Criteria:

1. Age 21 - 60 treatment-seeking right handed smokers.

2. Meet criteria for primary nicotine dependence confirmed by FTND and smoked at least
70% of days in the last 30 days prior to assessment.

3. General good health confirmed by history & physical.

4. Able to read and understand questionnaires and informed consent.

5. Motivated to quit, willing to set a target quit date (TQD) and abstain from smoking
after TDQ.

6. Participants must have a negative urine drug screen (UDS) and pregnancy test prior to
imaging sessions and beginning varenicline treatment.

7. Female participants will use a reliable method of birth control throughout the study.

8. Demonstrate subjective response to cues in a laboratory cue reactivity session.

Exclusion Criteria:

1. Currently meets DSM-IV criteria for any other psychoactive substance dependence
disorder except nicotine dependence.

2. Any psychoactive substance abuse within the last 30 days as evidenced by subject
report or urine drug screen.

3. Use of other tobacco products.

4. Current use of nicotine replacement therapy, bupropion, or other smoking cessation
treatment.

5. Previous failed attempt on varenicline.

6. Meets DSM-IV criteria for current axis I disorders of major depression, panic
disorder, obsessive compulsive disorder, post-traumatic stress syndrome, bipolar
affective disorder, schizophrenia, or any other psychotic disorder or organic mental
disorder.

7. Current suicidal ideation with plan or homicidal ideation.

8. Need for maintenance or acute treatment with any psychoactive medication including
anti-seizure medications which could potentially interfere with fMRI.

9. Clinically significant medical problems that would impair participation or limit
ability to participate in scan.

10. Sexually active females of child-bearing potential who are pregnant, nursing, or who
are not using a reliable form of birth control.

11. Has current charges pending for a violent crime (not including DUI related offenses).

12. Persons with ferrous metal implants or pacemaker since fMRI will be used.