Cannabinoids and pain responses: a possible role for prostaglandins.
The principal metabolite of delta 1-THC, delta 1-THC-7-oic acid exhibits significant analgesic action in the mouse hot plate test. The parent delta 1-THC has a similar effect when measured at later time points; however, 10 min after drug administration, a pronounced hyperalgesia is seen. This hyperalgesia can be inhibited by prior administration of either indomethacin or delta 1-THC-7-oic acid, presumably because of their ability to inhibit eicosanoid synthesis. Administration of prostaglandin E2 (PGE2), at doses that were a small fraction of the delta 1-THC given, resulted in a strong hyperalgesic response. Unlike delta 1-THC, the metabolite does not produce a cataleptic state in the mouse, which eliminates this as a basis for the hot plate response. The evidence presented is consistent with a mechanism in which the metabolite inhibits eicosanoid synthesis whereas the parent drug elevates tissue levels of prostaglandins.
Burstein
S H
SH
Department of Biochemistry, University of Massachusetts Medical School, Worcester 01655.
Hull
K
K
Hunter
S A
SA
Latham
V
V
D000698:Analgesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D006358:Hot Temperature; D006930:Hyperalgesia / Q000503:physiopathology*; D006941:Hyperesthesia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D010146:Pain / Q000503:physiopathology*; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*
D011453:Prostaglandins; C016780:11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid; D013759:Dronabinol; D007213:Indomethacin