Alcoholism
Conditions
Keywords
alcoholism /alcohol abuse, alcoholism antagonist, anticonvulsant, cognition, neuropharmacology, substance abuse related behavior, craving, euphoria, relapse /recurrence, patient oriented research
Brief summary
In the last decade, there has been an explosion of new knowledge of the neuroscientific basis of alcohol-seeking behavior. Briefly, medications that modulate mesolimbic dopamine pathways by facilitating gamma amino butyric function and inhibiting the action of excitatory amino acids should reliably diminish alcohol's rewarding effects. Topiramate (a sulfamate-substituted fructo-pyranose derivative) has these characteristics. In support of this concept, we have shown in a phase-II-type medications clinical trial that topiramate is significantly superior to placebo at improving drinking outcomes and decreasing craving among (N = 150) alcohol-dependent individuals. Using the carefully controlled environment of the human laboratory, we are submitting a revised application containing a set of systematic studies to assess directly the mechanistic neuropharmacological processes that are associated with topiramate's anti-drinking effects. This will provide a more comprehensive understanding of the neurobiology of alcohol-seeking behavior and aid in the development of even more effective compounds for the treatment of alcohol dependence. Thus, the specific aims of the project are to: 1) determine the dose-relationship of acute effects of topiramate to reduce alcohol effects related to its abuse and addiction potential. We hypothesize that topiramate will reduce alcohol-induced craving, reward, and euphoria; 2) determine whether chronic treatment with an acutely effective dose of topiramate produces substantial reductions in alcohol-related cue-induced craving, thereby decreasing the potential for treatment relapse. We hypothesize that chronic topiramate administration will desensitize (reduce) alcohol craving produced by alcohol-related sensory cues; and 3) determine whether topiramate interactions with and without alcohol are associated with neurocognitive impairment. Clinical studies including ours have suggested that topiramate use may be associated with neurocognitive effects such as loss of concentration and memory impairment. In our own study, these effects were mild and not associated with reduced treatment compliance. Since alcohol's ability to produce neurocognitive impairment may be mediated through similar ionic mechanisms to that of topiramate, the proposed human laboratory setting affords us the unique opportunity to more clearly delineate topiramate's neurocognitive effects in both the presence and absence of alcohol. This study supports NIAAA's goal to develop effective medications for treating alcoholism and to understand the basic underpinnings of the disease.
Interventions
DRUGTopiramate
200mg twice a day
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institutes of Health (NIH)
Bankole Johnson
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* DSM-IV-R diagnosis of alcohol dependence. * Drinking on average ≥14 and ≥21 drinks/week in the 30 days prior to enrollment for women and men, respectively, and describing a liking for and frequent use of beer as the alcohol-containing beverage. * Good physical health as determined by a complete physical examination, electrocardiogram within normal limits, and laboratory screening tests within acceptable range (see
Exclusion criteria
). * Negative pregnancy test at intake. Women of childbearing potential will be placed on oral contraceptives and also will be expected to use barrier and spermicide as an additional form of contraception if sexually active. * Literate in English language, and able to read, understand, and complete rating scales and questionnaires accurately. * Willingness to comply with study procedures and protocol including agreement to overnight stay at the human laboratory. Compliance with the alcohol, tobacco, and drug-free environment regulations at the human laboratory is also a condition of enrollment. * Written informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Reduction of alcohol-induced craving,reward,and euphoria | During testing days |
Secondary
| Measure | Time frame |
|---|---|
| Reductions in alcohol-related cue-induced associated with relapse | During testing days |
| Determine whether topiramate interactions with and without alcohol are associated with neurocognitive impairment | During testing days |
Countries
United States
Outcome results
None listed