RT Journal Article
SR Electronic
T1 HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 66
OP 75
DO 10.1124/jpet.115.226100
VO 355
IS 1
A1 Christeene G. Haj
A1 Percy F. Sumariwalla
A1 Lumír Hanuš
A1 Natalya M. Kogan
A1 Zhana Yektin
A1 Raphael Mechoulam
A1 Mark Feldmann
A1 Ruth Gallily
YR 2015
UL http://jpet.aspetjournals.org/content/355/1/66.abstract
AB Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ9-tetrahydrocannabinol (Δ9-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ9-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ9-THC–like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ9-THC–like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases.