Human Behavioral Pharmacology Laboratory (HBPL) Study of Varenicline's Impact on Cocaine and Alcohol Craving

Inclusion Criteria: 1. Subject is male or female and is between 21 and 65 years of age. 2. The subject has used cocaine, alcohol, or cocaine and alcohol at least once per month for at least the past year, and has used cocaine, alcohol, or cocaine and alcohol within 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. Meets DSM-IV criteria for current dependence on any substance other than nicotine, cocaine, alcohol or marijuana. 2. Subjects who are currently taking anti-depressant medications (e.g., SSRIs such as citalopram) 3. Patients who are diagnosed during screening with clinical depression using the HAM-D rating scale and present with a score \>10. 4. Subjects who are diagnosed with anxiety as diagnosed using the HAM-A anxiety scale with a score \>17 5. Subjects who meet current- or lifetime DSM-IV criteria for a psychotic disorder (e.g., schizophrenia) 6. Requires treatment with any psychotropic medication (e.g., antidepressant, antipsychotic, benzodiazepine, or mood stabilizing medication). 7. Subjects who test positive on the urine drug screen for any illicit drugs other than cocaine and marijuana during screening will be allowed a single retest. Those individuals who test positive for amphetamine during screening, given that they provide a copy of a prescription, will only be included if they can safely discontinue amphetamine use for the duration of the study. Subjects will need to provide a urine free of all illicit drugs other than cocaine and marijuana at study onset to be randomized. Subjects who test positive for any drugs other than marijuana prior to a study session will be allowed a single retest and a chance to reschedule their session. If the subject tests positive for any drug other than marijuana at the retest, their participation in the study will be terminated. 8. Use of any investigational medication within the past 30 days. 9. Concomitant use of any one of the following drugs or classes of drugs: Anti-depressant drugs such as citalopram, fluoxetine; antipsychotic drugs such as haloperidol; benzodiazepines or other anxiolytic medications; Antihypertensive drugs such as Reserpine, Verapamil; Blood thinners Medications used to treat respiratory diseases such as theophylline; Trimethoprim; Cimetidine; Antiepileptic drugs (AEDs) such as phenytoin or valproic acid. 10. Patients with a known hypersensitivity to varenicline. 11. Patients with severe unstable or serious medical illness such as a seizure disorder, unstable cerebrovascular disease, bronchospastic disease, hyperthyroidism, or diabetes mellitus. 12. Patients with known AIDS or other serious illnesses that may require hospitalization during the study. 13. Female subjects who are pregnant, plan to become pregnant, are currently lactating, or are of child-bearing potential and are not using acceptable methods of birth control; acceptable methods of birth control would include: 1. Barrier method (diaphragm or condom) 2. Intrauterine progesterone contraceptive system 3. Levonorgesterel implant 4. Medroxyprogesterone acetate contraceptive injection, or 5. Oral contraceptives. 14. Patients with impaired renal function, as indicated by corrected creatinine clearance below 60 ml/min as determined by the modified Cockcroft equation (CDC, 1986). 15. An unacceptable liver panel (liver function tests; LFTs) that may be indicative of hepatic dysfunction. 16. Clinical laboratory tests (e.g., CBC, blood chemistries, urinalysis) outside normal limits, as determined by PI. 17. 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). 18. Electrocardiography (EKG) indicative of 1st degree heart block, sinus tachycardia, left-axis deviation, non-specific ST or T-wave changes. 19. History of chest pain associated with cocaine use that prompted a visit to a physician. 20. Any medical or psychological condition that could jeopardize the subject's safe participation in the trial as determined by the PI.