Human Behavioral Pharmacology Laboratory Study of Varenicline's Impact on Cocaine Reinforcement

Inclusion Criteria 1. Males and females, 18 to 60 years old. 2. Recreational users of cocaine reporting at least six instances of cocaine use in the past 12 months and at least one use in the past 30 days. 3. Live within a commutable distance of the Treatment Research Center (TRC) at the Penn/VA Center for Studies of Addiction, University of Pennsylvania. We define this to be a distance within the service area of Septa, within an hour drive, or a distance that both the patient and Principal Investigator (PI) find acceptable. 4. Understands and signs the informed consent. Exclusion Criteria: 1. Current DSM-IV diagnosis of any psychoactive substance dependence other than nicotine dependence, as determined by the Structured Clinical Interview for the DSM (SCID). 2. Current severe psychiatric symptoms (e.g., psychosis, dementia, suicidal or homicidal ideation, mania or depression requiring anti-depressant therapy) as diagnosed using the SCID, the Hamilton Anxiety Rating Scale (Ham A), and Hamilton Ration Scale for Depression (HAM-D). 3. Individuals scoring \> 10 on the Hamilton Rating Scale for Depression (HAM-D). 4. Use of any investigational medication within the past 30 days. 5. Concomitant treatment with psychotropic medications. 6. Concomitant use of any one of the following drugs or classes of drugs: * Reserpine * Verapamil * theophylline, * trimethoprim, * cimetidine, * haloperidol, * benzodiazepines, or * antiepileptic drugs (AEDs). 7. Patients with a known hypersensitivity to varenicline. 8. Patients with severe concurrent illnesses such as bronchospastic disease, hyperthyroidism, diabetes mellitus. 9. Patients with known AIDS or other serious illnesses that may require hospitalization during the study. 10. Female subjects who are pregnant or lactating, or female subjects of child-bearing potential who are not using acceptable methods of birth control; acceptable methods of birth control include: * Barrier method (diaphragm or condom) with spermicide * Intrauterine progesterone contraceptive system * Levonorgesterel implant * Medroxyprogesterone acetate contraceptive injection, or * Oral contraceptives. 11. Patients with impaired renal function, as indicated by corrected creatinine clearance below 60 ml/min/70 kg as determined by the modified Cockcroft equation (CDC, 1986). 12. An unacceptable liver panel (liver function tests; LFTs) that may be indicative of hepatic dysfunction. 13. Clinical laboratory tests (e.g., CBC, blood chemistries, urinalysis) outside normal limits. 14. History of significant heart disease or dysfunction (e.g., an arrhythmia which required medication, Wolff Parkinson -White Syndrome, angina pectoris, documented history of myocardial infarction, heart failure). 15. Electrocardiography (EKG) indicative of 1st degree heart block, sinus tachycardia, left-axis deviation, non-specific ST or T-wave changes. 16. History of chest pain associated with cocaine use that prompted a visit to a physician.