“…The effects of cannabinoids through GPR55 have been investigated using different pharmacological approaches such as the [ 35 S]GTPγS-binding assay (measurement of GPR55 agonist-induced GDP-GTP exchange as an indicator of receptor activation), intracellular Ca 2+ transients, phosphorylation of ERK or activation of GTPase proteins and β-arrestin recruitment models (Oka et al 2007, 2009, Ryberg et al 2007, Lauckner et al 2008, WaldeckWeiermair et al 2008, Henstridge et al 2009, Kapur et al 2009, Ross 2009, 2011, Pertwee et al 2010, Whyte et al 2015, Zeng et al 2015. Moreover, in vivo studies have allowed a better knowledge of the physiological relevance of GPR55 signaling in processes such as energy metabolism (Romero-Zerbo et al 2011, Moreno-Navarrete et al 2012, Imbernon et al 2014, inflammation (Staton et al 2008), vascular function (Daly et al 2010), bone physiology (Whyte et al 2009), cancer (Perez-Gomez et al 2012, Andradas et al 2016 and GI disorders (Hasenoehrl et al 2016). Taking into account the large amount of physiological systems in which GPR55 is involved, the design of potent and tissue-specific GPR55 ligands remains an important field to develop new drugs.…”