THE ENHANCEMENT OF MORPHINE ANTINOCICEPTION IN MICE BY DELTA(9)-TETRAHYDROCANNABINOL

We have previously reported that intracerebroventricular or intratheca l administration of inactive doses of dg-tetrahydrocannabinol (THC) gr eatly enhance the antinociceptive potency of morphine in the mouse tai l-flick test. Experiments were conducted to test the hypothesis that m orphine's potency would be enhanced in mice receiving THC and morphine by conventional per os (PO) and subcutaneously (SC) routes of adminis tration. Antinociception was measured in the tail-flick test of radian t heat after administration of different combinations of THC and morph ine PO and SC Subcutaneous administration of THC (4 and 25 mg/kg) incr eased the potency of SC morphine 8.5- and 22.3-fold, respectively, whi le SC THC (25 mg/kg) increased the potency of PO morphine 3.1-fold. Pe r 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, morphin e's potency was significantly increased regardless of the enteral and parenteral routes of THC and morphine administration. The synthetic re ceptor selective cannabinoid CP-55, 940 (0.1 mg/kg, SC) also enhanced morphine's potency. Finally, the ability of the CB1 receptor antagonis t SR141716A to antagonize the enhancement of morphine by THC indicates that THC was acting through a cannabinoid receptor mechanism. (C) 199 8 Elsevier Science Inc.