The AAPS Journal

, Volume 11, Issue 1, pp 39–44 | Cite as

Targeting Fatty Acid Amide Hydrolase (FAAH) to Treat Pain and Inflammation

  • Joel E. Schlosburg
  • Steven G. Kinsey
  • Aron H. Lichtman
NIDA Symposium: Drugs of Abuse: Special Topics in Drug Development


The endogenous cannabinoid N-arachidonoyl ethanolamine (anandamide; AEA) produces most of its pharmacological effects by binding and activating CB1 and CB2 cannabinoid receptors within the CNS and periphery. However, the actions of AEA are short lived because of its rapid catabolism by fatty acid amide hydrolase (FAAH). Indeed, FAAH knockout mice as well as animals treated with FAAH inhibitors are severely impaired in their ability to hydrolyze AEA as well as a variety of noncannabinoid lipid signaling molecules and consequently possess greatly elevated levels of these endogenous ligands. In this mini review, we describe recent research that has investigated the functional consequences of inhibiting this enzyme in a wide range of animal models of inflammatory and neuropathic pain states. FAAH-compromised animals reliably display antinociceptive and anti-inflammatory phenotypes with a similar efficacy as direct-acting cannabinoid receptor agonists, such as Δ9-tetrahydrocannabinol (THC), the primary psychoactive constituent of Cannabis sativa. Importantly, FAAH blockade does not elicit any apparent psychomimetic effects associated with THC or produce reinforcing effects that are predictive of human drug abuse. The beneficial effects caused by FAAH blockade in these models are predominantly mediated through the activation of CB1 and/or CB2 receptors, though noncannabinoid mechanisms of actions can also play contributory or even primary roles. Collectively, the current body of scientific literature suggests that activating the endogenous cannabinoid system by targeting FAAH is a promising strategy to treat pain and inflammation but lacks untoward side effects typically associated with Cannabis sativa.

Key words

anandamide CB1 cannabinoid receptor CB2 cannabinoid receptor endogenous cannabinoid fatty acid amide hydrolase (FAAH) inflammatory pain neuropathic pain 



This research was supported by the following grants from the NIH: P50DA005274, R01DA015197, R01DA015683, P01DA009789, and T32DA007027.


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Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Joel E. Schlosburg
    • 1
  • Steven G. Kinsey
    • 1
  • Aron H. Lichtman
    • 1
  1. 1.Department of Pharmacology and Toxicology, Medical College of Virginia CampusVirginia Commonwealth UniversityRichmondUSA

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