Cannabinoids and pain responses: a possible role for prostaglandins

The principal metabolite of Δ 1 ‐THC, Δ 1 ‐THC‐7‐oic acid exhibits significant analgesic action in the mouse hot plate test. The parent Δ 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 Δ 1 ‐THC‐7‐oic acid, presumably because of their ability to inhibit eicosanoid synthesis. Administration of prostaglandin E 2 (PGE 2 ), at doses that were a small fraction of the Δ 1 ‐THC given, resulted in a strong hyperalgesic response. Unlike Δ 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.— B urstein , S. H.; H ull , K.; H unter , S. A.; L atham , V. Cannabinoids and pain responses: a possible role for prostaglandins. FASEB J. 2: 3022‐3026; 1988.