Inhibition of macrophage nitric oxide production by tetrahydrocannabinol in vivo and in vitro.

delta 9-Tetrahydrocannabinol (THC, 10 micrograms) was administered intraperitoneally to thioglycollate-treated mice. After 18 h, peritoneal macrophages were harvested and nitric oxide (NO.) production was induced by lipopolysaccharide (LPS, 1 microgram/ml) and interferon-gamma (IFN-gamma, 0.1-10 U/ml). Macrophages from THC-treated mice produced about half as much NO. as controls. THC (1 microgram/ml) added in vitro caused further inhibition. Greater inhibition was observed at the lower (0.1-0.3 U/ml) IFN-gamma concentrations. The results suggest that the use of THC can reduce NO. production and thereby affect host defense mechanisms, inflammation and autoimmune responses.