The purpose of the study was to evaluate the effect of delta-9-tetrahydrocannabinol (THC), the major psychoactive constituent of marijuana, on ischemic neuronal injury. A 12-min ischemic insult was induced by a reduction in systolic blood pressure to a mean of 50 mm Hg, followed by bilateral carotid artery occlusion at a middle ear temperature of 37.5 degrees C. THC at either a low (0.1 mg/kg; n=8) or high (10 mg/kg; n=8) dose was injected i.p. every 12 h for 7 days prior to ischemia. Non-treated ischemic (n=8) animals formed the control group. The animals were sacrificed 3 weeks post-ischemia for quantitative histopathology. THC at either dose did not significantly reduce ischemic neuronal damage in the hippocampus. The high dose THC-treated group showed significantly less neocortical injury, compared to either the control or low-dose THC groups (p<0.05). The striatum was markedly protected by both low and high dose THC (p<0.001). This regionally specific protection implies that either the hippocampus undergoes suprathreshold ischemic injury or that mechanisms of ischemic injury vary in different brain regions.