Comparative characterization in the rat of the interaction between cannabinoids and opiates for their immunosuppressive and analgesic effects

In the present work, we investigated in the rat the possibility of function al interaction between opiate and cannabinoid systems at immune level compa ratively with the central nervous system (CNS). Moderate analgesic doses of the synthetic cannabinoid compound CP-55,940 (0.2 mg/kg, i.p.) and morphin e (5 mg/kg, s.c.) significantly inhibited the ConA-induced splenocyte proli feration and natural killer (NK) cytolytic activity. The acute co-administr ation of the two drugs resulted in an enhancement of antinociception while they did not yield any additive inhibition of the immune parameters. The CB I cannabinoid receptor antagonist N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-( 2,4-dichlorophenyl)-4-methy1-1H-pyrazole-3-carboxamide (SR141716A, 3 mg/kg, i.p.) and the CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethhyl bicycl o[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazol e-3-carboxamide (SR144528; 3 mg/kg, i.p.) did not block the central nor the immune effects of morphine; similarly, the opioid receptor antagonist nalo xone did not attenuate CP-55,940-induced effects. Animals tolerant to CP-55 ,940-induced (0.2 mg/kg, Lp. twice a day for 4 days) or morphine-induced an algesia (5 mg/kg, s.c.; twice a day for 6 days) also developed tolerance to their acute immunosuppressive effects. Concomitantly, animals became cross -resistant to the immunosuppressive effects while an asymmetric cross-toler ance developed for analgesia. Our data demonstrated the existence of an int eraction between cannabinoids and opiates at the immune level that differs from the interaction present in the CNS. (C) 2001 Elsevier Science B.V. All rights reserved.