Assessment of Tolerance to Immunosuppressive Activity of Δ9-Tetrahydrocannabinoll in Rats

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Abstract
Immunosuppression evoked by Δ9-tetrahydrocannabinol (Δ9-THC) has been a consistent finding in rats but the development of tolerance to this phenomenon has not been explored. Therefore, Fischer rats of both sexes were orally given Δ9-THC at 6 or 12 mg/kg or sesame oil as vehicle control for 5–26 days before and after I.P. antigenic stimulation with sheep red blood cells (SRBC). Δ9-THC doses were relevant to those of man and produced mild CNS-inhibition followed by CNS-stimulation, tolerance developing to both behavioral phases. The primary immune response was evaluated by determining splenic antibody-forming cells (AFC), hemagglutinin (HT) and/or hemolysin (HS) titers. Simultaneous administration of Δ9-THC and SE induced dose-related splenic atrophy and reduced AFC proliferation as well as HT and HS responses. These changes were not elicited by sesame oil. Tolerance did not develop to imnunosuppression during 26 days of cannabinoid treatment. A9-THC given 3 days post SEBC inoculation induced immunosuppression at 12 but not 6 mg/kg. Immunosuppression was directly related to Δ9-THC rather than to non-specific debilitating factors since body weights are stable. The inductive phase of the primary immune response was most sensitive to impairment although the reproductive phase was also affected at the high dose level.