This four week inpatient, placebo controlled, randomized clinical trial is designed to assess the effects of once daily amiloride (10 mg) or aspirin (325 mg) on regional cerebral blood flow (rCBF) defects identified in 75 chronic cocaine users. Previous work by our group and others have identified persistent decreases in CBF with specific focal defects that may be partially reversible after four weeks of pharmacotherapy. The rationale for use of amiloride and aspirin is our recent finding that cocaine abusers have significant activation of platelets that predisposes them to aggregate and form thrombi in small blood vessels. These platelet thrombi may be the basis for the reversible defects in rCBF. Aspirin through dense granule activity and amiloride through alpha granule activity can reverse this platelet activation and more rapidly dissolve these cocaine induced thrombi. In pilot work we found that cocaine users with focal rCBF defects had a 29% improvement in these defects when treated with aspirin for 4 weeks. Defects in rCBF were assessed using technetium 99m-D, L-hexamethyl propyleneamine oxime (HMPAO) and single photon emission computed tomography (SPECT). Our group and others have also found neuropsychological testing abnormalities (NPA) in cocaine abusers. The relationship of these rCBF deficits to NPA will also be ascertained at baseline and after 2 and 4 weeks of this trial.
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