Effects of Varenicline on Brain Activity During Nicotine Abstinence

Not Applicable

Completed

Brief Summary: This project aims to define mechanisms through which varenicline might be an effective smoking cessation medication.

Detailed Description: Thirty treatment seeking smokers will be recruited to complete a 40-day within-subject (cross-over), double-blind study that will assess effects of varenicline on brain activation while performing certain tasks. Prior to beginning the study, participants will complete an health and physical screening to determine final eligibility. Following a medication run-up and a 3.5 day abstinence period, participants will complete study period 1 (an fMRI scan while performing attention, working memory and emotion tasks). After a 14 to 21-day washout period the study procedures will be repeated with placebo (order of study medication counterbalanced). After completion of both study periods, all participants will be offered a 13-week quit smoking program with varenicline.

Recruitment & Eligibility

Inclusion Criteria

Treatment-seeking smokers between the ages of 18 and 65, that smoke at least 10 cigarettes/day for at least the past 6 months
Provide a baseline CO (carbon monoxide) reading of >10ppm
Provide written informed consent and are fluent, English-speaking
Weight of equal to or less than 300 lbs

Exclusion Criteria

Smoking Behavior

Use of chewing tobacco, snuff or cigars
Current enrollment or plans to enroll in another smoking cessation program in the next 5 months
Plan to use other nicotine substitutes or smoking cessation treatments in the next 5 months
Provide a baseline CO (carbon monoxide) reading ≤10 ppm

Alcohol/Drug Exclusion Criteria

History of substance abuse and/or currently receiving treatment for substance abuse
Current alcohol consumption that exceeds 25 standard drinks/week
A breath alcohol concentration reading ≥ 0.01 at the H&P (health & physical) screening or either of the lab sessions

Medication Exclusion Criteria

Medical Exclusion Criteria

Women who are pregnant, planning a pregnancy, or lactating;
History or current diagnosis of psychosis, current major depression, bipolar disorder, ADHD, schizophrenia, or any Axis 1 disorder as identified by the MINI
Serious or unstable disease within the past 6 months (heart disease, HIV)
Diagnosis of cancer in the past 6 months or if successful treatment for cancer has not ended within the past 6 months
History of epilepsy or a seizure disorder
History or current diagnosis (last 6-months) of abnormal rhythms and/or tachycardia (>100 beats/minute); history or current diagnosis of COPD (chronic obstructive pulmonary disease), cardiovascular disease (stroke, angina, coronary heart disease), heart attack in the last 6 months, uncontrolled hypertension (SBP>150 or DBP>90)
History of kidney and/or liver failure (including transplant)
History of head trauma or prior seizure; family history of a seizure disorder, brain (or central nervous system) tumor
Use of pacemakers, certain metallic implants, or presence of metal in the eye as contraindicated for MRI (magnetic resonance imaging);
Low or borderline intellectual functioning - determined by receiving a score <80 on the Shipley verbal IQ Test
Non-English speaking; determined at phone screen
History of claustrophobia (contraindicated for MRI) or color blindness (task requires color recognition); self-report at telephone screen
Being left-handed
Any fore-limb deformity
Wearing cochlear implant or bi-lateral hearing aids

General Exclusion

Any medical condition or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator and/or Study Physician.
Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.
Any physical or visual impairment that may prevent the individual from using a computer keyboard or completing any study tasks.

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Varenicline	Varenicline	-

Primary Outcome Measures

Name	Time	Method
Percent Change BOLD Signal	Day 13	We calculated the percent BOLD signal change while performing the N-back task between the varenicline vs. placebo session. We subtracted BOLD signal observed during the 0-back condition from the BOLD signal observed during the 3-back condition (3back minus 0-back)We controlled for relevant co-variates such as sex, nicotine dependence level and education.

Secondary Outcome Measures

Name	Time	Method
Effect of Varenicline Treatment on Task Performance (N-back Correct Response Time)	Day 13	We examined the difference in correct reaction time on the N-back task between varenicline and placebo treatment. Models included terms for the main effect of treatment period (varenicline vs. placebo), memory load (0-back, 1-back, 2-back, 3-back) and covariates. We tested for interactions between nicotine dependence severity and treatment.