@article {Gallily918, author = {Ruth Gallily and Aviva Yamin and Yaakov Waksmann and Haim Ovadia and Joseph Weidenfeld and Avi Bar-Joseph and Anat Biegon and Raphael Mechoulam and Esther Shohami}, title = {Protection Against Septic Shock and Suppression of Tumor Necrosis Factor α and Nitric Oxide Production by Dexanabinol (HU-211), a Nonpsychotropic Cannabinoid}, volume = {283}, number = {2}, pages = {918--924}, year = {1997}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Dexanabinol, HU-211, a synthetic cannabinoid devoid of psychotropic effects, improves neurological outcome in models of brain trauma, ischemia and meningitis. Recently, HU-211 was found to inhibit brain tumor necrosis factor (TNFα) production after head injury. In the present study, we demonstrate the ability of HU-211 to suppress TNFα production and to rescue mice and rats from endotoxic shock after LPS (Escherichia coli 055:B5) inoculation. In BALB/c mice, a dose of 10 mg/kg LPS, injected i.p., caused 57\% and 100\% mortality, at 24 and 48 hr, respectively. HU-211, administered i.p. 30 min before lipopolysaccharide (LPS), reduced lethality to 9 and 67\% at these time points (P \< .05). When coinjected withd-galactoseamine (i.p.), LPS was 100\% lethal within 24 hr, whereas eight hourly injections of HU-211 caused mortality of C57BL/6 mice to drop to 10\% (P \< .001). Administration of LPS to Sprague-Dawley rats resulted in a 30\% reduction in the mean arterial blood pressure within 30 min, which persisted for 3 hr. HU-211, given 2 to 3 min before LPS, completely abolished the typical hypotensive response. Furthermore, the drug also markedly suppressed in vitro TNFα production and nitric oxide generation (by \>90\%) by both murine peritoneal macrophages and rat alveolar macrophage cell line exposed to LPS. HU-211 may, therefore, have therapeutic implications in the treatment of TNFα-mediated pathologies. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/283/2/918}, eprint = {https://jpet.aspetjournals.org/content/283/2/918.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }