CELLULAR IMMUNE FUNCTION IN MICE TOLERANT TO OR ABSTINENT FROM L-TRANS-DELTA(9)-TETRAHYDROCANNABINOL

The effects of tolerance to l-trans-Delta(9)-tetrahydrocannabinol (THC ) following repeated administration and of subsequent abstinence follo wing drug withdrawal on the cellular immune function were determined i n female B6C3F1 mice. Mice were injected with THC (10 mg/kg s.c.) twic e daily for 4 days. On day 5, analgesic response to various doses of T HC was determined using the tail flick test. Similarly, hypothermic re sponse to THC was also determined. Multiple injections of THC resulted in the development of tolerance to both the analgesic and hypothermic effects of THC, Immune function studies were performed on mice render ed tolerant to or abstinent from THC by these procedures. Neither tole rance nor abstinence subsequent to a 4-day THC administration had any effect on either body weight or thymus weight and cellularity, althoug h both spleen weight and cellularity were decreased in THC-abstinent a nimals. Likewise, no significant effects on B cell proliferation were observed in either tolerant or abstinent mice. The production of the c ytokine interleukin-2 by T helper cells was markedly suppressed in bot h tolerant and abstinent mice, whereas the production of interleukin-4 was significantly suppressed only in THC-abstinent mice. Significant suppression of tumor cell cytolysis mediated by cytotoxic T cells and natural killer cells was only observed in THC-abstinent mice. These re sults suggest that THC-mediated modulation of the immune response may result from a differential effect on cellular populations.