Possible pharmacological probes for predicting and preventing relapse in treated alcoholics.

Relapse is a frequent problem for recovered alcoholics since up to 80% do so within 6 months of completing treatment. Although the mechanisms underlying relapse are unknown, several internal and external cues have been associated with it. Desire (or craving) for alcohol is an internal cue which may precipitate relapse and is amenable to physiological and pharmacological studies. Recent studies have indicated that pharmacological manipulations of the serotonergic system can produce variations in craving for alcohol. For example, when challenged with the putative serotonin1 (5-HT1) agonist, m-chlorophenylpiperazine (m-CPP), alcoholics report increases in craving and desire for alcohol (George et al, 1990). In our studies with moderately dependent alcoholics, 5-HT uptake inhibitors (e.g., citalopram) reduced both the craving for and the consumption of alcohol. Studies are underway to identify the mechanism underlying these findings. Other systems may also regulate alcohol craving. However, some agents which allegedly decreased alcohol intake in animals, such as enalapril, an angiotensin converting enzyme inhibitor, showed no effect on desire for or intake of alcohol in humans. A better understanding of the neural and systemic mechanisms underlying alcohol craving may help us in the prediction and/or prevention of relapse in treated alcoholics.