5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid

It has been recently reported that cannabidiol (CBD), a nonpsychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation. However, the underlying biochemical mechanisms were not clarified. In the present study, we performed biochemical analysis of the effect of CBD both in vivo, by using glioma tumor tissues excised from nude mice, and in vitro, by using U87 glioma cells. In vivo exposure of tumor tissues to CBD significantly decreased the activity and content of 5-lipoxygenase (LOX, by similar to 40%), and of its end product leukotriene B-4 (similar to 25%). In contrast cyclooxygenase (COX)-2 activity and content, and the amount of its end product prostaglandin E-2, were not affected by CBD. In addition, in vivo treatment with CBD markedly stimulated (similar to 175%) the activity of fatty acid amide hydrolase (FAAH), the main anandamide-degrading enzyme, while decreasing anandamide content (similar to 30%) and binding to CB, cannabinoid receptors (similar to 25%).