This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a small, open-label pilot study of memantine in the treatment of alcohol dependence. The primary objective of this study is to compare post-treatment versus pre-treatment drinking behaviors and craving (quantity and frequency, as well as desire to drink), as assessed by the TLFB method, and the AUQ, in subjects treated with memantine and coping skills therapy.
The Specific Aim i s to conduct an open-label, 8-week pilot study of the tolerability and potential efficacy of memantine, a non-competetive NMDA receptor antagonist at a flexible dosage of 5-20 mg/day in 20 subjects with alcohol dependence receiving ambulatory psychosocial treatment. Memantine is a non-competetive NMDA receptor antagonist which is FDA approved for the treatment of moderate-to-severe Alzheimer's disease. The drug has demonstrated safety and tolerability in thousands of patients in Europe and the United States (M2003, Parsons et al. 1999). It has been postulated that memantine may also be of benefit in a number of other conditions, including other neurodegenerative disorders, brain injury, HIV dementia, chronic pain, among others (Parsons et al. 1999). Several recent experiments with memantine and other non-competitive NMDA receptor antagonists in rats have demonstrated a possible role for these compounds in reducing alcohol craving, preventing the development of physiological alcohol dependence, and reducing alcohol intake in alcohol-dependent animals (H lter et al. 1996, 2000; Kotli ska, 2001). This, combined with its demonstrated safety and tolerability when administered with alcohol (Bisaga and Evans 2004) and its low abuse potential (Parsons et al. 1999), makes memantine a candidate for the treatment of alcoholism. Although there are no reports of memantine trials in alcoholism, the drug is similar to acamprosate, another non-competitive NMDA receptor antagonist, which has shown efficacy in the treatment of alcoholism. Numerous European studies of acamprosate have shown benefit in the maintenance of abstinence and the reduction of relapse risk in alcoholism (Anton and Swift 2003). In addition to its effects on NMDA receptors, memantine also has been shown in vitro to be a 5-HT3 receptor antagonist at concentrations that produce NMDA receptor antagonism (Rammes et al 2001). Ondansetron, a 5-HT3 receptor antagonist, has demonstrated efficacy in reducing relapse and craving in early-onset alcoholics (Johnson et al. 2000; Kranzler et al. 2003), Based on these findings and memantine's activity at 5-HT3 receptors, the drug could have its greatest effects among early-onset alcoholics.
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