New Medications to Treat Alcohol Dependence
Condition: Alcoholism
MeSH terms: Alcoholism
Study type: Interventional
Phase: Phase 2

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.
    


Intervention name(s): Topiramate
Intervention type(s): Drug
Intervention description(s): 200mg twice a day
Other intervention name(s): Topamax
Intervention MeSH terms: Topiramate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: alcoholism /alcohol abuse; alcoholism antagonist; anticonvulsant; cognition; neuropharmacology; substance abuse related behavior; craving; euphoria; relapse /recurrence; patient oriented research