The enhancement of morphine antinociception in mice by Δ9-tetrahydrocannabinol

We have previously reported that intracerebroventricular or intrathecal administration of inactive doses of dg-tetrahydrocannabinol (THC) greatly enhance the antinociceptive potency of morphine in the mouse tail-flick test. Experiments were conducted to test the hypothesis that morphine's potency would be enhanced in mice receiving THC and morphine by conventional per os (PO) and subcutaneously (SC) routes of administration. Antinociception was measured in the tail-flick test of radiant heat after administration of different combinations of THC and morphine PO and SC Subcutaneous administration of THC (4 and 25 mg/kg) increased the potency of SC morphine 8.5- and 22.3-fold, respectively, while SC THC (25 mg/kg) increased the potency of PO morphine 3.1-fold. Per os administration of THC (10 and 20 mg/kg) increased the potency of SC and PO morphine 11.4-fold and 7.6-fold, respectively. Thus, morphine's potency was significantly increased regardless of the enteral and parenteral routes of THC and morphine administration. The synthetic receptor selective cannabinoid CP-55, 940 (0.1 mg/kg, SC) also enhanced morphine's potency. Finally, the ability of the CB1 receptor antagonist SR141716A to antagonize the enhancement of morphine by THC indicates that THC was acting through a cannabinoid receptor mechanism. (C) 1998 Elsevier Science Inc.