Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications

Roger G. Pertwee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)


The endocannabinoid system consists of cannabinoid CB1 and CB2 receptors, of endogenous agonists for these receptors known as "endocannabinoids', and of processes responsible for endocannabinoid biosynthesis, cellular uptake and metabolism. There is strong evidence first, that this system up-regulates in certain disorders as indicated by an increased release of endocannabinoids onto their receptors and/or by increases in the expression levels or coupling efficiency of these receptors, and second, that this up-regulation often appears to reduce or abolish unwanted effects of these disorders or to slow their progression. This discovery has raised the possibility of developing a medicine that enhances up-regulation of the endocannabinoid system associated with these disorders by inhibiting the cellular uptake or intracellular metabolism of an endocannabinoid following its "autoprotective' endogenous release. For inhibition of endocannabinoid metabolism, research has focused particularly on two highly investigated endocannabinoids, anandamide and 2-arachidonoyl glycerol, and hence on inhibitors of the main anandamide-metabolising enzyme, fatty acid amide hydrolase (FAAH), and of the main 2-arachidonoyl glycerol-metabolising enzyme, monoacylglycerol (MAG) lipase. The resulting data have provided strong preclinical evidence that selective FAAH and MAG lipase inhibitors would ameliorate the unwanted effects of several disorders, when administered alone or with a cyclooxygenase inhibitor, and that the benefit-to-risk ratio of a FAAH inhibitor would exceed that of a MAG lipase inhibitor or dual inhibitor of FAAH and MAG lipase. Promising preclinical data have also been obtained with inhibitors of endocannabinoid cellular uptake. There is now an urgent need for clinical research with these enzyme and uptake inhibitors.

Original languageEnglish
Pages (from-to)96-105
Number of pages10
JournalProceedings of the Nutrition Society
Issue number1
Early online date18 Oct 2013
Publication statusPublished - Feb 2014
EventThe Nutrition Society Scottish Section: Conference on ‘PUFA mediators: implications for human health’ Symposium 3: Cannabinoids in human health - Pollock Halls, Edinburgh, United Kingdom
Duration: 18 Mar 201319 Mar 2013

Bibliographical note

R. G. P. is grateful for financial support from both GW
Pharmaceuticals and the National Institute on Drug

Financial Support
The work was supported by Research grants from the
National Institute on Drug Abuse (grant numbers
DA-009789 and DA-03672) and funding from GW


  • Fatty acid amide hydrolase inhibitors
  • Monoacylglycerol lipase inhibitors
  • Endocannabinoids
  • Anandamide and 2-arachidonoyl glycerol
  • Cannabinoid CB1 and CB2 receptors


Dive into the research topics of 'Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications'. Together they form a unique fingerprint.

Cite this