Δ9-tetrahydrocannabinol (Δ9-THC) prevents cerebral infarction via hypothalamic-independent hypothermia

Δ9-tetrahydrocannabinol (Δ9-THC), a primary psychoactive constituent of cannabis, has been reported to act as a neuroprotectant via the cannabinoid CB1 receptor. In this study, Δ9-THC significantly decreased the infarct volume in a 4 h mouse middle cerebral artery occlusion mouse model. The neuroprotective effect of Δ9-THC was completely abolished by SR141716, cannabinoid CB1 receptor antagonist, and by warming the animals to 31 °C. Δ9-THC significantly decreased the rectal temperature, and the hypothermic effect was also inhibited by SR141716 and by warming to 31 °C. At 24 h after cerebral ischemia, Δ9-THC significantly increased the expression level of CB1 receptor in both the striatum and cortex, but not in the hypothalamus. Warming to 31 °C during 4 h cerebral ischemia did not increase the expression of CB1 receptor at the striatum and cortex in MCA-occluded mice. These results show that the neuroprotective effect of Δ9-THC is mediated by a temperature-dependent mechanism via the CB1 receptor. In addition, warming to 31 °C might attenuate both the neuroprotective and hypothermic effects of Δ9-THC through inhibiting the increase in CB1 receptor in both the striatum and cortex but not in the hypothalamus, which may suggest a new thermoregulation mechanism of Δ9-THC.