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

Endocannabinoid signaling at the periphery: 50 years after THC.

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Center of Integrated Research, Campus Bio-Medico University, Rome, Italy; Center for Brain Research, Santa Lucia Foundation IRCCS, Rome, Italy. Electronic address:
Bone Laboratory, Hebrew University Medical Faculty, Jerusalem, Israel; Institute for Drug Research, Hebrew University Medical Faculty, Jerusalem, Israel.
DE-MTA 'Lendület' Cellular Physiology Research Group, Department of Physiology, Medical Faculty, University of Debrecen, Debrecen, Hungary.
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA, USA.
Division of Reproductive Sciences, Cincinnati Children's Research Foundation, Cincinnati, OH, USA.
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Council of Research, Pozzuoli, Italy.
Department of Obstetrics and Gynaecology, Sidra Medical and Research Center, Doha, Qatar.
National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA.
Institute for Drug Research, Hebrew University Medical Faculty, Jerusalem, Israel.
Hotchkiss Brain Institute, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Alberta, Canada.
Institute of Molecular Psychiatry, University of Bonn, Bonn, Germany.


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.


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

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