Cocaine- and methamphetamine-induced acute cerebral vasospasm: an angiographic study in rabbits

Stroke is a frequently reported, though uncommon, complication of drug abuse, primarily cocaine. The pathogenesis is uncertain, although such cerebrovascular events may result from sympathetically mediated vasoconstriction of cerebral vessels. Amphetamine, another sympathomimetic amine that is commonly abused, may also cause strokes by producing cerebral vasospasm and/or vasculitis. Amphetamine and its derivatives are frequent adulterants of illegally obtained cocaine and may also be used concurrently; the effect(s) of this combination of drugs upon the cerebral vasculature is not known. Our aim was to develop an animal model that would enable us to study the ability of these drugs to produce acute cerebral vasospasm and to observe the response to IV administration of amphetamine and cocaine, either alone or together. Magnified basilar artery arteriograms were obtained in 12 New Zealand white rabbits before and after IV administration of cocaine, methamphetamine, or both, at various dosages. Low doses produced mild vasodilatation. At higher doses, the animals who received cocaine and methamphetamine alone showed little or no basilar artery spasm, but coadministration produced definite basilar artery vasospasm, reflecting a synergistic vasoconstrictive effect. If a similar response exists in the human cerebral vasculature, then this could help explain the cause of strokes associated with drug abuse.