The Potential of Inhibitors of Endocannabinoid Metabolism for Drug Development: A Critical Review

  • Christopher J. FowlerEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 231)


The endocannabinoids anandamide and 2-arachidonoylglycerol are metabolised by both hydrolytic enzymes (primarily fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL)) and oxygenating enzymes (e.g. cyclooxygenase-2, COX-2). In the present article, the in vivo data for compounds inhibiting endocannabinoid metabolism have been reviewed, focussing on inflammation and pain. Potential reasons for the failure of an FAAH inhibitor in a clinical trial in patients with osteoarthritic pain are discussed. It is concluded that there is a continued potential for compounds inhibiting endocannabinoid metabolism in terms of drug development, but that it is wise not to be unrealistic in terms of expectations of success.


2-Arachidonoylglycerol Anandamide Cyclooxygenase-2 Drug development Fatty acid amide hydrolase Monoacylglycerol lipase Pain 









Arachidonoyl ethanolamide, anandamide




Fatty acid amide hydrolase


Fatty acid binding protein 5


Guanosine 5′-O-(3-[35S]thio)triphosphate






Monoacylglycerol lipase


N-Acylethanolamine-hydrolyzing acid amidase




Nonsteroidal anti-inflammatory drug






Transient receptor potential (vanilloid) 1 ion channels



The author thanks the Swedish Science Council (Grant no. 12158, medicine) and the Research Funds of the Medical Faculty, Umeå University, for their financial support of his research.


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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Pharmacology and Clinical NeuroscienceUmeå UniversityUmeåSweden

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