Effect of Varenicline on Tobacco Addiction and on Abstinence-induced Cognitive Impairment

Background: \- Varenicline (Chantix ) is a drug that is approved by the Food and Drug Administration (FDA) to help people stop smoking. Varenicline is very effective in helping some people quit smoking, but is less effective for others. Researchers are interested in conducting more in-depth studies into how varenicline works, including its effect on smokers' responses to items that may trigger cigarette cravings, in order to develop better smoking cessation medications. Objectives: \- To examine the effectiveness of varenicline as an effective medication for tobacco addiction by studying its effect on nicotine reinforcement, nicotine-seeking behavior, cue-elicited craving, and performance impairment and craving after overnight tobacco deprivation. Eligibility: \- Individuals between 18 and 50 years of age who have been smoking at least 10 cigarettes per day for at least 2 years. Design: * This study will require 12 study visits. Some visits will be brief and other visits that involve test sessions will last up to 8 hours. If no sessions are repeated, the study will take 26 days. Participants will not be required to attempt to quit smoking during this study. * Participants will be screened with a full physical examination and medical history, blood and urine tests, and other tests as required by the study researchers. * Participants will take two sets of pills during the study: the first set during the first 12 days of the study, followed by a 2-day break, then the second set during the last 12 days. Some of the pills will contain varenicline, and others will be placebos. * On Day 1 of the study, participants will come to the National Institute on Drug Abuse to receive the first set of pills. Participants will take the first pill before leaving. * On Day 8, participants will have a training session that will measure the amount of carbon monoxide in the breath. Participants will also complete several questionnaires about smoking habits and current mood, and wil