Endocannabinoid signaling at the periphery: 50 years after THC

Trends Pharmacol Sci. 2015 May;36(5):277-96. doi: 10.1016/j.tips.2015.02.008. Epub 2015 Mar 18.


In 1964, the psychoactive ingredient of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC), was isolated. Nearly 30 years later the endogenous counterparts of THC, collectively termed endocannabinoids (eCBs), were discovered: N-arachidonoylethanolamine (anandamide) (AEA) in 1992 and 2-arachidonoylglycerol (2-AG) in 1995. Since then, considerable research has shed light on the impact of eCBs on human health and disease, identifying an ensemble of proteins that bind, synthesize, and degrade them and that together form the eCB system (ECS). eCBs control basic biological processes including cell choice between survival and death and progenitor/stem cell proliferation and differentiation. Unsurprisingly, in the past two decades eCBs have been recognized as key mediators of several aspects of human pathophysiology and thus have emerged to be among the most widespread and versatile signaling molecules ever discovered. Here some of the pioneers of this research field review the state of the art of critical eCB functions in peripheral organs. Our community effort is aimed at establishing consensus views on the relevance of the peripheral ECS for human health and disease pathogenesis, as well as highlighting emerging challenges and therapeutic hopes.

Keywords: bone; cardiovascular system; female and male reproductive system; gastrointestinal tract; immune system; liver; localization; muscle; signaling pathways; skin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cannabinoid Receptor Agonists / pharmacokinetics
  • Cannabinoid Receptor Agonists / pharmacology*
  • Cannabinoid Receptor Agonists / therapeutic use
  • Dronabinol / pharmacokinetics
  • Dronabinol / pharmacology*
  • Dronabinol / therapeutic use
  • Endocannabinoids / metabolism*
  • Humans
  • Organ Specificity
  • Signal Transduction*
  • Tissue Distribution


  • Cannabinoid Receptor Agonists
  • Endocannabinoids
  • Dronabinol