Hyporesponsiveness to the immunosuppressant effects of delta-8-tetrahydrocannabinol

Delta-9-tetrahydrocannabinol (delta 9-THC) and delta 8-THC have previously been shown to suppress humoral immunity in mice. The purpose of these investigations was to determine whether a hyporesponsiveness develops to the immunosuppressive effect of delta 8-THC. BALB/c mice were administered 60 mg/kg delta 8-THC i.p. 2 days after an i.p. immunizing dose of sheep erythrocytes (sRBC). Significant inhibition of direct hemolytic plaque-forming cells (PFC)/spleen was observed on days 3--6, with peak day of inhibition occurring on day 4. The effective inhibiting dose 50 (ED50) measured on peak day of response was 40 mg/kg for PFC/10(6) spleen cells and 38 mg/kg for PFC/spleen. When mice were pretreated daily for 5 days with different doses of delta 8-THC, similar ED50's were detected. Under this pretreatment regimen, 5 or 10 mg/kg produced no immunosuppression. Daily treatment with 5 or 10 mg/kg delta 8-THC for 5 days prior to sRBC and varying doses of delta 8-THC administered 2 days after sRBC resulted in significantly higher ED50's and increased values for the slopes of the dose response curves. These results suggest that a hyporesponsiveness develops to the immunosuppressive activity of delta 8-THC.