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.
Burstein
S H
SH
Department of Biochemistry, University of Massachusetts Medical School, Worcester.
Audette
C A
CA
Doyle
S A
SA
Hull
K
K
Hunter
S A
SA
Latham
V
V
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D051379:Mice; D009288:Naproxen / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D001095:Arachidonic Acids; D002186:Cannabinoids; D006893:Hydroxyeicosatetraenoic Acids; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D009288:Naproxen; D013759:Dronabinol