Missing Pieces to the Endocannabinoid Puzzle.

Mauro Maccarrone

Journal: Trends in molecular medicine 2021;26(3):263-272

PMID: 31822395

Full Text on Elsevier Science View on PubMed

Abstract

The most bioactive ingredient of cannabis (Cannabis sativa or indica) extracts, Δ-tetrahydrocannabinol (THC), was identified in the 1960s as one of more than 110 phytocannabinoids. It activates receptors of chemically different endogenous ligands (endocannabinoids) that, unlike THC, are metabolized by several enzymes of the endocannabinoid system. Here, the complexity of the plant-derived and endogenous cannabinoids (eCBs) is discussed, to better appreciate the challenge of: (i) dissecting their mutual interactions; (ii) understanding their impact on human pathophysiology; and (iii) exploiting them for human disease. To this aim, missing pieces to the eCB puzzle must be urgently found, by solving the 3D structures of key components, and interrogating noncanonical modes of regulation and trafficking of these lipid signals.

Address: Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy; European Center for Brain Research, IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Rome, Italy. Electronic address: [email protected].

DOI: 10.1016/j.molmed.2019.11.002

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MeSH Terms: Cannabis, Dronabinol, Endocannabinoids, Humans, Receptors, Cannabinoid, Signal Transduction