Psychoactive and non-psychotropic cannabinoid constituents of marijuana have been discovered by this lab to possess potential value as antiischaemic agents. These compounds were identified to be potent antioxidants, which appears to account for their protective activity in cell culture models of cerebral ischaemia. The precise mechanism(s) by which cannabinoids protect have been evaluated and will continue to be examined over the course of the next year. We have ascertained a direct role for cannabinoids as free radical scavengers, and are currently examining their specificity as antiinflamatory enzyme inhibitors and their involvement in preventing cytokine release. Investigation of the non-psychoactive cannabinoid, Cannabidiol, as a treatment for cerebral ischaemia and head injury is also underway due to collaborative efforts with physicians at George Washington University and USUHS (respectively). Preliminary results indicate that a single dose of cannabidiol (administered immediately post- injury) can reduce ischaemic damage and neurological impairment by 60%. In addition, studies to examine the physiological role of the cannabinoid receptor are being undertaken. Cannbinoid receptor activation appears to protect neurons from AMPA/kainate type glutamate toxicity by a mechanism independent of calcium channels. Other G-protein coupled receptors are currently being examined, in order to ascertain whether cannabinoid receptors are unique in their ability to protect against glutamate toxicity or whether this is a property common to many Gi-protein coupled receptors.
