Cocaine Dependence
Conditions
Keywords
Vigabatrin, GABA levels, Smoked cocaine
Brief summary
The objective of this study is to determine if vigabatrin will decrease cocaine self-administration, cardiovascular effects, subjective effects and craving compared to placebo.
Detailed description
Two recent open label clinical trials have reported that the anticonvulsant, gamma vinyl-GABA (GVG; vigabatrin), decreases relapse to cocaine use (Brodie et al., 2003, 2005). Vigabatrin increases neural GABA levels by irreversibly inhibiting the primary GABA degradation enzyme, GABA-transaminase; the hypothesized mechanism by which vigabatrin decreases cocaine relapse is by increasing GABA levels, thereby decreasing the effects of cocaine and cocaine-associated environmental cues on extracellular dopamine concentrations in the mesolimbic dopaminergic pathway (Morgan and Dewey, 1998). We are proposing to use our model of repeated dose cocaine self-administration to assess the interaction between vigabatrin and smoked cocaine under controlled laboratory conditions. This 57-day outpatient/inpatient /outpatient/inpatient protocol will evaluate the effects of vigabatrin maintenance (0, 3 g/day) on cocaine craving, subjective effects, and self-administration using a within-subjects design. Non-treatment seeking cocaine-dependent volunteers will be maintained outpatient for 14 days of vigabatrin maintenance prior to beginning each inpatient study phase. During the inpatient phases, volunteers will live on a hospital clinical research unit and will participate in laboratory sessions in which they will have the opportunity to purchase doses of smoked cocaine (0, 12, 25, 50 mg; $5/administration). In addition to measuring cocaine self-administration, we will measure the cardiovascular and subjective effects of repeated cocaine administration and cocaine craving under each vigabatrin maintenance condition. Determining vigabatrin's effects on a range of smoked cocaine doses will provide essential data on the mechanism of the vigabatrin-cocaine interaction.
Interventions
DRUGVigabatrin
DRUGCocaine
Sponsors
Novel Cocaine Pharmacotherapies
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Meets DSM-IV criteria for current cocaine abuse * Average use of smoked cocaine is at least 2x/week for past 6 mos; currently spends at least $70 per week on cocaine * Has patterns of smoked cocaine use in terms of frequency and amounts which parallel or exceed those administered in the study * Age 21-45 * Able to give informed consent, and comply with study procedures * Agrees to practice an effective form of contraception
Exclusion criteria
* Current seizure disorder or heart disease * Currently meeting DSM-IV criteria for all major psychiatric/psychotic disorders. Volunteers with a history of depression or psychosis will also be excluded (p. 43, Investigator's brochure) * Dependence on substances other than cocaine or nicotine * Request for drug treatment * Judged to be noncompliant with study protocol * Clinical laboratory tests outside normal limits that are unacceptable to the study physician (e.g., BP \> 140/90; BUN, creatinine, LFTs \> 1.5 ULN; hematocrit \< 34 for women, \< 36 for men; pseudocholinesterase deficiency) * Current parole or probation * Recent history of significant violent or suicidal behavior * Pregnancy or lactation * Baseline visual field defects
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Subjective effects | — |
| Cardiovascular effects | — |
| Cravings | — |
| Cocaine Administration | — |
Countries
United States
Outcome results
None listed