Although a great amount of research has been conducted to resolve cocaine dependence, an effective treatment has yet to be discovered. Topiramate is a drug that was found to be useful in treating alcohol dependence. The purpose of this study is to determine the effectiveness of topiramate in treating cocaine dependent individuals.

Despite considerable scientific effort in the last two decades to develop treatment for cocaine dependent individuals, no medication has proven to be effective for treating cocaine dependence. Cocaine's rewarding effects are primarily a result of altering nerve pathways involving dopamine, a naturally-occurring chemical in the brain. Past research has focused on developing medications that either block dopamine or inhibit its release. However, these medications have not proven effective in treating cocaine dependence. This study will evaluate a new strategy of treating cocaine dependence by altering dopamine's functional expression. Dopamine-associated expression may be mediated through inhibition of gamma-aminobutyric acid (GABA), another brain chemical. Topiramate is a GABA inhibitor that has proven effective in treating alcohol dependent individuals. The purpose of this study is to determine the efficacy of topiramate in treating cocaine dependent individuals.

Participants will be randomly assigned to receive either 300 mg per day of topiramate or placebo. In addition, participants will receive weekly cognitive behavioral therapy for 12 weeks. Follow-up visits will occur at 2 weeks and 1, 2, and 3 months following completion of treatment, and will include evaluations of cocaine use and psychosocial functioning.

Inclusion Criteria:

• Current DSM-IV diagnosis of cocaine dependence
• Seeking treatment for cocaine dependence
• At least one positive urine drug screen, within the 2 weeks prior to study entry
• If female, a negative pregnancy test prior to study entry
• Agrees to use an effective method of contraception for the duration of the study
• Reads and writes English
• Willing to participate in behavioral treatment for cocaine dependence

Exclusion Criteria:

• Current DSM-IV diagnosis of dependence on any psychoactive substance other than cocaine, alcohol, nicotine, caffeine, or marijuana
• Physiological dependence on alcohol and requires medical detoxification
• Neurological or psychiatric disorders
• Organic brain disease
• Dementia
• Bulimia and/or anorexia nervosa
• Seizure disorders or epilepsy
• History of suicide attempts and/or current suicidal ideation, as determined by the SCID, within the 30 days prior to study entry
• Mandated by the court to obtain treatment for cocaine dependence
• Expected to relocate from the study area
• AIDS diagnosis, or a CD4 cell count less than 500 mm
• Active or history of syphilis
• Severe or life-threatening adverse reaction to any medications the year prior to study entry
• Currently receiving active treatment with topiramate
• Use of a drug with known potential for toxicity to a major organ system (e.g., isoniazid, methotrexate), within 30 days prior to study entry
• Pregnant or breastfeeding
• Concurrent pharmacotherapy with psychotropics, including antidepressants, anxiolytics, antipsychotics, anticonvulsants, and psychomotor stimulant-type medications, within the two weeks prior to study entry
• Use of St. John's Wort, yohimbine, ginko biloba, horehound, or any other central nervous system active herbal preparations within the 2 weeks prior to study entry
• Use of any opiate substitutes (e.g., methadone, levo-alpha acetyl methadol, buprenorphine), within the month prior to study entry
• Clinically significant test results that, in the investigator's opinion, may interfere with study participation
• Fever of unknown origin or neuroleptic malignant syndrome
• Serious medical co-morbidity requiring medical intervention or close supervision
• Received inpatient or outpatient treatment for cocaine dependence within the 4 weeks prior to study entry
• Past participation in a clinical trial utilizing topiramate
• Treatment with electroconvulsive therapy within the 3 months prior to study entry
• Member of the same household of an individual enrolled in the present study