MOLECULAR PHARMACOLOGY, 50:334-341 (1996). Attenuation of Inducible Nitric Oxide Synthase Gene Expression by L\9-Tetrahydrocannabinol Is Mediated through the Inhibition of Nuclear Factor-KB/Rel Activation

9-Tetrahydrocannabinol (9-THC), a prototypic compound belonging to the family of agents known as cannabinoids, produces a wide variety of biological effects, including inhibi-tion of immune function. The putative mechanism for cannabi-noid biological action involves binding to cannabinoid receptor types 1 and 2 (CB1 and CB2) to negatively regulate adenylate cyclase and inhibit intracellular signaling via the cAMP cas-cade. In the current study, we show that z9-THC produces a marked inhibition of inducible nitric oxide synthase (iNOS) tran-scription and nitric oxide production by the macrophage line RAW 264.7 in response to lipopolysaccharide (LPS). Analysis of RAW 264.7 cell RNA demonstrated transcripts for CB2 but not CB1. Treatment of RAW 264.7 with z9-THC inhibited forskolin-stimulated cAMP production in a dose-related manner, verify-ing the expression of functional cannabinoid receptors by thi