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. 2021 Oct 28;15:747229. doi: 10.3389/fnins.2021.747229

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Copyright © 2021 de Melo Reis, Isaac, Freitas, de Almeida, Schuck, Ferreira, Andrade-da-Costa and Trevenzoli.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The endocannabinoid system (ECS) is composed of lipid endocannabinoids (eCBs), allosteric (lipoxins and resolvins) and peptide (hemopressin derivatives) mediators, their receptors (the cannabinoid type 1 (CB1) and type 2 (CB2), which are activated by phyto- (THC, CBD, and possibly many others) and synthetic cannabinoids (represented by WIN55,212-2, a mixed agonist), metabolic enzymes (FAAH and MAGL, and others) and membrane transporters. Upon activation, CB1 and CB2 signal through fast (Ca²⁺ and K⁺ currents) and/or slow pathways, as cyclic AMP-protein kinase A (cAMP-PKA), ıextracellular signal-regulated (ERK), beta-arrestin, mitogen-activated protein kinase (MAPK) and PI3K; in addition, gene transcription is also turned on by nuclear receptors (PPARγ and others).