Interaction between Opioids and Cannabinoids in the Immune System: Functional Evidence in the Rat

Cannabinoids and opioids share several pharmacological properties, including antinociception, hypothermia, sedation, hypotension and inhibition of immune function. It has been demonstrated that chronic morphine treatment in rats produced hypersensitivity to Δ9-tetrahydrocannabinol analgesia. As a consequence of those results and the fact that drug abusers often use marijuana and morphine concurrently, we have investigated the possibility of functional interaction between opioid and cannabinoid systems at immune level in the rat. We have evaluated splenocyte proliferative response to a mitogen and natural killer cytolytic activity following chronic administration of the synthetic cannabinoid compound CP-55,940, and morphine. A psychotropic dose of CP-55,940 (0.2 mg kg−1, i.p.) significantly inhibited the splenocyte proliferative response to Concanavalin A and natural killer activity. Similar to the effects of CP-55,940, morphine (5 mg kg−1, s.c.) administration was also accompanied by a significant suppression of both parameters. Animals that received daily injection of either CP-55,940 or morphine developed tolerance to their acute immunosuppressive effects. Once tolerance to the suppressive effects of either cannabinoid or morphine was achieved, animals became cross-resistant to the suppressive effect of either drug. These data suggest the possibility that morphine and CP-55,940 have a common underlying mechanism for the suppression of splenocyte proliferation and natural killer activity.