Selective inhibition of FAAH produces antidiarrheal and antinociceptive effect mediated by endocannabinoids and cannabinoid-like fatty acid amides
J. Fichna, M. Sałaga, J. Stuart, D. Saur, M. Sobczak, H. Zatorski, J. -P. Timmermans, H. B. Bradshaw, K. Ahn and M. A. Storr
Article first published online: 3 DEC 2013 | DOI: 10.1111/nmo.12272
The endogenous cannabinoid system (ECS) is implicated in several physiological and pathophysiological functions in the gastrointestinal (GI) tract, including motility and pain signaling. Finding that natural and synthetic cannabinoid (CB) receptor ligands are able to penetrate into the central nervous system (CNS) causing adverse side effects, such as impaired cognition and motor control, prompted the search for novel safer therapeutics targeting the ECS. The main finding of the study is that selective inhibition of fatty acid amide hydrolase (FAAH) activity regulates intestinal motility and pain signaling in physiological and pathophysiological conditions indirectly, through the CB receptors and possibly also the non-CB sites via changes in the levels of endogenous cannabinoids. Moreover, there were no CNS-related side effects of selective inhibition of FAAH. Our observations give new opportunities for the design of novel treatments for functional GI ailments, including diarrhea-predominant irritable bowel syndrome (IBS-D).