Certain atypical antipsychotic medications (particularly clozapine) or combinations of medications are useful to treat alcohol or other substance abuse, particularly in the general (non-schizophrenic) population. Generally stated, one aspect of the invention features a method of treating a patient suffering from alcohol or other substance abuse by administering to the patient medication effective to rectify an abuse-associated dysfunction in t he DA-mediated brain reward circuit. A second aspect of the invention features administering medication that strongly antagonizes .alpha.2 andrenergic receptors and weakly antagonizes dopamine D2 receptors. Preferably, the rati o of .alpha.2 receptor blockade to D2o receptor blockade is similar to that of clozapine. The medication may be a single compound (such as clozapine or risperidone), or it may include two or more compounds which together achieve the specified function. For example, the medication may include a first component which weakly blocks the D2 receptor (such as clozapine, quetiapine or ziprasidone or a low dose of another anti-psychotic that is a more potent D2 blocker) and a5 second component (such as clozapine, risperidone or idazoxan) which strongly blocks .alpha.2 receptors, particularly the .alpha. 2C receptor. Cocktails of the twocomponents are also disclosed.
TREATING ALCOHOL AND OR SUBSTANCE ABUSE BY ANTAGONIZING .ALPHA. 2 ADRENERGIC RECEPTORS WITH WEAK DOPAMINE BLOCKING