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

• Age 21 - 60 treatment-seeking right handed smokers.
• Meet criteria for primary nicotine dependence confirmed by FTND and smoked at least 70% of days in the last 30 days prior to assessment.
• General good health confirmed by history & physical.
• Able to read and understand questionnaires and informed consent.
• Motivated to quit, willing to set a target quit date (TQD) and abstain from smoking after TDQ.
• Participants must have a negative urine drug screen (UDS) and pregnancy test prior to imaging sessions and beginning varenicline treatment.
• Female participants will use a reliable method of birth control throughout the study.
• Demonstrate subjective response to cues in a laboratory cue reactivity session.

Exclusion criteria

• Currently meets DSM-IV criteria for any other psychoactive substance dependence disorder except nicotine dependence.
• Any psychoactive substance abuse within the last 30 days as evidenced by subject report or urine drug screen.
• Use of other tobacco products.
• Current use of nicotine replacement therapy, bupropion, or other smoking cessation treatment.
• Previous failed attempt on varenicline.
• 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.
• Current suicidal ideation with plan or homicidal ideation.
• Need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications which could potentially interfere with fMRI.
• Clinically significant medical problems that would impair participation or limit ability to participate in scan.
• Sexually active females of child-bearing potential who are pregnant, nursing, or who are not using a reliable form of birth control.
• Has current charges pending for a violent crime (not including DUI related offenses).
• Persons with ferrous metal implants or pacemaker since fMRI will be used.