Effectiveness of GABA Agonists in Reducing the Reinforcing Effects of Cocaine

GABA Agonists as Pharmacotherapies for Cocaine Abuse

Cocaine abuse continues to represent a significant public-health concern. Cocaine likely creates its addictive effects by increasing levels of dopamine, a chemical found in the brain. GABA agonists are chemicals that have the opposite effect of cocaine by inhibiting the release of dopamine. The purpose of this study is to determine whether GABA agonists reduce the psychological and physiological reinforcing effects of cocaine.

Cocaine likely creates its reinforcing and addictive effects by increasing levels of dopamine, a brain neurotransmitter. GABA agonists are chemicals that have the opposite effect by inhibiting the release of dopamine. Increasing GABA activity may result in greater inhibition of dopamine systems, which may lead to new treatments for cocaine abuse. The purpose of this study is to determine whether pretreatment with GABA agonists reduces the psychological and physiological reinforcing effects of cocaine. Specifically, the study will look at three different GABA agonists: tiagabine, baclofen, and trazolam.

This double-blind, placebo-controlled study will involve three separate experimental phases; each phase will last 4 weeks and will test one of three GABA agonists (tiagabine, baclofen, or trazolam). Daily testing sessions will last approximately 6 hours. One of four GABA agonist dose treatments will be administered. Participants will then be introduced to a sample dose of intranasal cocaine. This will allow the participants to become acquainted with the drug effects of the corresponding cocaine dose for that day (0.444, 5, 10, or 20 mg). Subjective, physiological, and performance measures will be obtained. This will be followed by a period of cocaine self-administration. Participants will be given the opportunity to work on a computer to obtain additional single unit doses of cocaine. A total of 8 unit doses of cocaine will be available during each daily session. At the end of the daily session, additional subjective measures will be evaluated with questionnaires. Overall, a total of 16 GABA agonist-cocaine dose combinations will be administered on 16 different days. A subgroup of participants will also undergo similar procedures with the option to acquire money instead of cocaine. At the end of the study, all participants will be offered a referral to an appropriate drug-abuse treatment program.

Inclusion Criteria:

• Recent use of cocaine
• Meets DSM-IV diagnostic criteria for psychoactive substance abuse or dependence for cocaine
• Positive drug urine screen for cocaine at time of initial screening interview
• Reports self-administration of at least 1,260 mg of cocaine during the 4 weeks prior to study start date
• Body Mass Index (BMI) of less than 29
• Females must use an effective form of contraception throughout the study

Exclusion Criteria:

• Meets DSM-IV diagnostic criteria for psychoactive substance dependence for substances other than cocaine or nicotine
• Currently seeking treatment for substance abuse/dependence
• Current or past history of physical disease, impaired cardiovascular functioning, chronic obstructive pulmonary disease
• History of seizure, head traumas, or central nervous system tumors
• Current or past history of serious psychiatric disorder other than substance abuse or dependence
• Family history of cardiovascular disease or seizure disorders