Inclusion Criteria

1. Male and females 18 years of age or older.
2. Subject meets DSM-IV criteria for current diagnose of cocaine dependence, determined by The Structured Clinical Interview for DSM-IV (SCID-IV).
3. Subject used cocaine in the past 30 days totaling at least $200 worth of cocaine. Cocaine use will be determined by utilizing the modified Timeline Followback, crosschecked with the ASI, which inquires about dollar amounts spent on drug use.
4. Subject lives a commutable distance from the TRC and agrees to attend all research visits, including follow-up visits.
5. Subject speaks, understands, and prints in English.
6. Written informed consent signed by the subject.

Exclusion Criteria

1. Subjects mandated to treatment based upon a legal decision or as a condition of employment.
2. Subjects with evidence of current substance dependence other than cocaine, alcohol or nicotine dependence, as determined by the SCID-IV.
3. Subjects who meets DSM-IV criteria for current alcohol dependence who require a medical alcohol detoxification.
4. Requires treatment with any psychoactive medications, including any anti-seizure medications (with the exception of Benadryl used sparingly, if necessary, for sleep).
5. Has a lifetime DSM-IV diagnosis of bipolar affective disorder, schizophrenia or any psychotic disorder, or organic mental disorder. Has current DSM-IV diagnosis of any other clinically significant psychiatric disorder that will interfere with study participation, as determined by the study physician or PI (Drs. Kyle Kampman, Charles Dackis and Helen Pettinati).
6. Female subjects who are pregnant or lactating, or female subjects of childbearing potential who are not using acceptable methods of birth control. Acceptable methods of birth control include: barrier (diaphragm or condom) with spermicide, intrauterine progesterone contraceptive system, levonorgestrel implant, medroxyprogesterone acetate contraceptive injection, and oral contraceptives.
7. Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits that are clinically unacceptable to the Principal Investigator. 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. Eligibility will be determined by most recent lab results collected prior to randomization.
8. Subjects with impaired renal function as indicated by corrected creatinine clearance below 80 ml/min/70 kg as determined by the modified Cockcroft equation (Center for Disease Control, 1986).
9. Subjects who have any disease of the gastrointestinal tract, liver or kidneys that could result in a possibility of altered metabolism or excretion of the study drug. As it is not possible to enumerate the many conditions which might impair absorption, metabolism, or excretion, the investigators will be guided by evidence such as: History of major gastrointestinal tract surgery (gastrectomy, gastrostomy, bowel resection, etc) or a history of an active peptic ulcer or chronic disease of the GI tract (ulcerative colitis, regional enteritis, or gastrointestinal bleeding).
10. History of significant heart disease (an arrhythmia which required medication, angina pectoris, documented history of myocardial infarction, or heart failure).
11. Known hypersensitivity to acamprosate.
12. Subjects having participated in any investigational drug trial within 30 days prior to randomizing into the study.
13. Subjects with any serious illnesses that may require hospitalization during the study, as determined by the study physician or PI (Drs. Kyle Kampman, Charles Dackis and Helen Pettinati).