Cannabidiol, a non-psychoactive constituent of cannabis, has been reported as a neuroprotectant. Cannabidiol and Δ 9-tetrahydrocannabinol, the primary psychoactive constituent of cannabis, significantly decreased the infarct volume at 4 h in the mouse middle cerebral artery occlusion model. The neuroprotective effects of Δ 9-tetrahydrocannabinol but not cannabidiol were inhibited by SRI41716, a cannabinoid CBI receptor antagonist, and were abolished by warming of the animals to the levels observed in the controls. Δ 9-Tetrahydrocannabinol significantly decreased the rectal temperature, and the hypothermic effect was inhibited by SRI41716. These results surely show that the neuroprotective effect of Δ 9- tetrahydrocannabinol are via a CBI receptor and temperature-dependent mechanisms whereas the neuroprotective effects of cannabidiol are independent of CBI blockade and of hypothermia.
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