The principal metabolite of Δ1-THC, Δ1-THC-7-oic acid exhibits significant analgesic action in the mouse hot plate test. The parent Δ1-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 Δ1-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 Δ1-THC given, resulted in a strong hyperalgesic response. Unlike Δ1-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.; Hull, K.; Hunter, S. A.; Latham, V. Cannabinoids and pain responses: a possible role for prostaglandins. FASEB J. 2: 3022-3026; 1988.