A Phase II Trial of Varenicline for the Treatment of Cocaine Dependence

Inclusion Criteria:

1. Males and females, 18 to 65 years old.

2. Meets DSM-IV criteria for Cocaine Dependence, as determined by the Structured
Clinical Interview for DSM-IV (SCID).

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 cocaine,
alcohol, or nicotine dependence, as determined by the SCID.

2. Subject is, in the investigator's opinion, at risk of requiring medical
detoxification for alcohol dependence during the study.

3. Concomitant treatment with psychotropic medications.

4. Current gambling problems. This will be assessed by the patient's self-report.

5. Patients mandated to treatment based upon a legal decision or as a condition of
employment who will use participation in this study to fulfill to their court
mandated treatment requirement.This will be assessed by the patient's self-report.

6. Current severe psychiatric symptoms, e.g., psychosis, dementia, suicidal or homicidal
ideation, mania or depression requiring antidepressant therapy in the opinion of the
Principal Investigator (PI).

7. Use of any investigational medication within the past 30 days.

8. Subject has serious heart, lung, kidney, immune system, GI tract (ulcerative colitis,
regional enteritis, or gastrointestinal bleeding) disease.

9. Current use of naltrexone, disulfiram, modafinil, stimulants, haloperidol,
benzodiazepines or anticonvulsants.

10. Known hypersensitivity to varenicline.

11. Patients with known AIDS or other serious illnesses that may require hospitalization
during the study.

12. 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:

1. barrier (diaphragm or condom) with spermicide

2. intrauterine progesterone contraceptive system

3. levonorgestrel implant

4. medroxyprogesterone acetate contraceptive injection

5. oral contraceptives

6. tubal ligation.

13. Patients with impaired renal function as indicated by corrected creatinine clearance
below 60 ml/min as determined by the modified Cockcroft equation (CDC, 1986).

14. Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits
that are clinically unacceptable to the Medical Director. EKG 1st degree heart block,
sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are
allowed; liver function tests [LFTs] <5 x ULN are acceptable).