5-hydroxy-6-8-11-14-eicosatetraenoic-acid and 11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic-acid

Cannabinoids have been shown to affect various aspects of arachidonic acid metabolism both in vivo and in vitro. Eicosanoid metabolites of arachidonate and related octadecanoate are believed to be involved in cell adhesion processes as agonists in some instances and as antagonists in other cases. This report shows data in which cannabinoids exhibit marked inhibitory effects on the adhesion of mouse peritoneal cells to polystyrene culture dishes. The effects could be seen by in vivo administration of the drugs as well as by direct exposure of the cells in vitro. The data suggest that this inhibition of adhesion is mediated by one or more products generated by stimulation of a lipoxygenase pathway.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Cell Adhesion; Cells, Cultured; Dronabinol; Ethanol; Hydroxyeicosatetraenoic Acids; Indomethacin; Isomerism; Leukocytes; Male; Masoprocol; Mice; Mice, Inbred Strains; Prostaglandins; Reference Values

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.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Cannabinoids; Dronabinol; Edema; Female; Hydroxyeicosatetraenoic Acids; Mice; Naproxen; Platelet Activating Factor; Structure-Activity Relationship