Immunosuppressive effects of 8,9-epoxyhexahydrocannabinol (EHHC)

Abstract

8,9-Epoxyhexahydrocannabinol (EHHC)-treated mice showed an inhibition of both humoral and cell-mediated immunity. The hemolytic plaque forming assay was employed to determine both the IgM and IgG antibody response. The effect of EHHC on IgM antibody production was measured in BDG1 male mice given X 10(8) sheep erythrocytes i.p. followed 24 and 48 hours later by i.p. injections of EHHC. EHHC produced a dose-dependent inhibition of plaque forming cells (PFC)/10(6) spleen cells and PFC/spleen on days 3, 4 and 5 after antigen administration. On day 4 the ED50 for PFC/10(6) spleen cells and PFC/spleen was 28 and 18 mg/kg, respectively. Peak response to IgG antibody production was observed on day 9. EHHC (100 mg/kg) administered i.p. 48 hours after antigen produced a 58 and 46% suppression of PFC/10(6) leucocyte on days 7 and 9, respectively. CDF1 male mice received 100 microng of Cornybacterium parvum in the left footpad. Two days after sensitization, EHHC was administered in doses of 0.75 to 50 mg/kg i.p. A challenge dose of 100 microng of Cornybacterium parvum was injected into the right footpad on day 6 and footpad swelling was measured 24 hours later by mercury displacement. EHHC at a dose of 0.78 mg/kg produced a 95% inhibition of the delayed-type hypersensitivity response. These studies showed that EHHC inhibits both the humoral and cellular arm of the immune response.