Topiramate for Alcohol and Cocaine Dependence (TOP2)

Inclusion Criteria: Male and females, 18 years or older. Meets DSM(Diagnostic and Statistical Manual)-IV criteria for current diagnoses of cocaine and alcohol dependence, determined by the SCID (Structured Clinical Interview for the DSM)-IV. In the past 30 days, used no less than $200-worth of cocaine and meets the following drinking criteria as measured by the Timeline Followback (TLFB) (Sobell and Sobell, 1995) a. drank within 30 days of intake day, b. reports a minimum of 48 standard alcoholic drinks (avg. 12 drinks/wk) in a consecutive 30-day period over the 90-day period prior to starting intake (i.e., a minimum of 40% days drinking), and c. has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males and 4 or more drinks per day in females) in this same pre-treatment period. Two consecutive days of abstinence from cocaine and alcohol, determined by self-reports and confirmed by negative urine toxicology screens, a negative breathalyzer tests, and collateral report, a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan et al., 1989) score below eight,. Subjects will be encouraged to achieve 3 consecutive days of abstinence, however, subjects who have achieved 2 consecutive days of abstinence will be included with the approval of the principal investigator. We anticipate that these subjects will comprise less than 5% of total enrolled subjects. Subjects will be given 2 additional weeks beyond the screening week to attain the appropriate period of cocaine and alcohol abstinence prior to randomization. Lives a commutable distance from the Treatment Research Center (TRC) and agrees to attend all research visits including follow-up visits. Speaks, understands, and prints in English. Exclusion Criteria: Abstinent from cocaine or alcohol for 30 consecutive days prior to signing consent form. Meets DSM-IV criteria for dependence on any substance other than cocaine and alcohol (except nicotine and cannabis), determined by the SCID. Needs treatment with any psychoactive medications including any anti-seizure medications (with the exception of Benadryl used sparingly, if necessary, for sleep). Current use of phenytoin or any drug of similar class. Meets DSM-IV criteria for schizophrenia or any psychotic disorder, or organic mental disorder. Subject meets current DSM-IV diagnosis of any other clinically significant psychiatric disorder that will interfere with study participation. Has evidence of a history of significant hematological, pulmonary, endocrine, cardiovascular, renal or gastrointestinal disease. Severe physical or medical illnesses such as AIDS, active hepatitis, significant hepatocellular injury as evidenced by elevated bilirubin levels (>1.3), or elevated levels (over 3.5x normal) of aspartate aminotransferase (AST), and serum glutamic-pyruvic transaminase (SGPT) after the required 3 days of abstinence, or severe renal disease, severe respiratory diseases or severe diarrhea with resulting metabolic acidosis, serum bicarbonate (< 20 milliequivalent (mEq)/L) History of epilepsy or seizure disorder. Use of an investigational medication in the 30 days prior to randomization. History of nephrolithiasis (kidney stones). History of hypersensitivity to topiramate. Is female and tests positive on a pregnancy test, is contemplating pregnancy in the next 6 months, is nursing, or is not using an effective contraceptive method (if relevant). Acceptable methods of contraception include barrier methods (diaphragm or condom with spermicide, intrauterine progesterone contraceptive system, levonorgestrel implant, and medroxyprogesterone acetate contraceptive injection). Current use of a carbonic anhydrase inhibitor. A history of glaucoma