Endocannabinoid signaling at the periphery: 50 years after THC

Mauro Maccarrone, Itai Bab, Tamás Bíró, Guy A. Cabral, Sudhansu K. Dey, Vincenzo Di Marzo, Justin C. Konje, George Kunos, Raphael Mechoulam, Pal Pacher, Keith A. Sharkey, Andreas Zimmer

Research output: Review article

267 Citations (Scopus)


In 1964, the psychoactive ingredient of Cannabis sativa, Δ9-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.

Original languageEnglish
Article number1213
Pages (from-to)277-296
Number of pages20
JournalTrends in Pharmacological Sciences
Issue number5
Publication statusPublished - máj. 1 2015

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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    Maccarrone, M., Bab, I., Bíró, T., Cabral, G. A., Dey, S. K., Di Marzo, V., Konje, J. C., Kunos, G., Mechoulam, R., Pacher, P., Sharkey, K. A., & Zimmer, A. (2015). Endocannabinoid signaling at the periphery: 50 years after THC. Trends in Pharmacological Sciences, 36(5), 277-296. [1213]. https://doi.org/10.1016/j.tips.2015.02.008