Effectiveness of GABA Agonists in Reducing the Reinforcing Effects of Cocaine

This study has been completed.
Sponsor:
Information provided by:
National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier:
NCT00218166
First received: September 16, 2005
Last updated: December 31, 2007
Last verified: December 2007
  Purpose

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.


Condition Intervention Phase
Cocaine-Related Disorders
Drug: GABA Agonists
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: GABA Agonists as Pharmacotherapies for Cocaine Abuse

Further study details as provided by National Institute on Drug Abuse (NIDA):

Primary Outcome Measures:
  • Progressive-ratio break point [ Time Frame: Measured during each experimental session ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Subjective effects of cocaine [ Time Frame: Measured during each experimental session ] [ Designated as safety issue: No ]
  • Physiological measures [ Time Frame: Measured throughout the study ] [ Designated as safety issue: Yes ]

Enrollment: 78
Study Start Date: August 2001
Study Completion Date: May 2005
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: A
Within subject design
Drug: GABA Agonists
GABA drugs administered acutely by mouth
Other Name: Triazolam, tiagabine, baclofen

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00218166

Locations
United States, Kentucky
University of Kentucky Medical Center
Lexington, Kentucky, United States, 40536 0086
Sponsors and Collaborators
Investigators
Principal Investigator: Craig Rush ACT
  More Information

No publications provided

Responsible Party: Craig R. Rush, University of Kentucky
ClinicalTrials.gov Identifier: NCT00218166     History of Changes
Other Study ID Numbers: DA013567, R01-13567-1, DPMC
Study First Received: September 16, 2005
Last Updated: December 31, 2007
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Additional relevant MeSH terms:
Cocaine-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Substance-Related Disorders
GABA Agonists
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014