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.
D000818:Animals; D000893:Anti-Inflammatory Agents; D002186:Cannabinoids / Q000494:pharmacology*; D005260:Female; D007109:Immunity / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D002186:Cannabinoids; D007166:Immunosuppressive Agents