Antagonism to the actions of platelet activating factor by a nonpsychoactive cannabinoid

A recent report from our laboratory gave evidence showing that tetrahydrocannabinol (THC)-7-oic acid has antinociceptive activity in the mouse. We also pointed out that this substance, which is a major metabolite of THC in most species including humans, is probably responsible for the well known analgesic properties of the parent drug. The present report contains findings that suggest THC-7-oic acid may have considerable activity as an antagonist to platelet activating factor, which may also explain the known properties of THC as a bronchodilator, antipyretic and antirheumatic agent. In the mouse ear edema test, THC-7-oic acid appeared to be about as efficacious as phenidone; however, its potency was less than either phenidone or indomethacin. When compared with the parent drug, THC, in the platelet activating factor-induced paw edema assay, it acted more quickly and produced a greater reduction of edema. This is consistent with the possibility that THC must be metabolized to the 7-oic acid for activity to be seen. Its activity in preventing platelet activating factor-induced mortality was comparable to naproxen. In vitro studies suggest that THC-7-oic acid can inhibit both cyclooxygenase and 5-lipoxygenase activities in intact cells.