Structure-activity relationships of natural and synthetic cannabinoids in suppression of humoral and cell-mediated immunity.

Delta-9-Tetrahydrocannabinol (delta-9-THC) a psychoactive constituent of marihuana, has been shown in previous studies to suppress humoral and cell-mediated immunity. The objective of this study was to determine whether structural modification of delta-9-THC would result in a more potent immunosuppressant agent devoid of central nervous system activity. The ED50 for reduction of the humoral immune response to sheep erythrocytes as measured by spleen plaque forming cells/10(6) spleen cells was 70 mg/kg for delta-9-THC. Delta-8-THC, 1-methyl delta-8-THC and abnormal delta-8-THC were more potent with ED50 values of 14, 13 and 8 mg/kg, respectively. Cell-mediated immunity was evaluated by a delayed-type hypersensitivity response to sheep erythrocytes. At doses of 100 mg/kg s.c. for 4 days, the cannabinoids suppressed the delayed-type hypersensitivity response from 35 to 64%. These data show that the cannabinoids can cause immunosuppression which is not related to central nervous system activity since 1-methyl delta-8-THC and abnormal delta-8-THC have minimal central nervous system activity.