Is lipid signaling through cannabinoid 2 receptors part of a protective system?

Abstract

The mammalian body has a highly developed immune system which guards against continuous invading protein attacks and aims at preventing, attenuating or repairing the inflicted damage. It is conceivable that through evolution analogous biological protective systems have been evolved against non-protein attacks. There is emerging evidence that lipid endocannabinoid signaling through cannabinoid 2 (CB 2 ) receptors may represent an example/part of such a protective system/ armamentarium. Inflammation/tissue injury triggers rapid elevations in local endocannabinoid levels, which in turn regulate signaling responses in immune and other cells modulating their critical functions. Changes in endocannabinoid levels and/or CB 2 receptor expressions have been reported in almost all diseases affecting humans, ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, auto-immune, lung disorders to pain and cancer, and modulating CB 2 receptor activity holds tremendous therapeutic potential in these pathologies. While CB 2 receptor activation in general mediates immunosuppressive effects, which limit inflammation and associated tissue injury in large number of pathological conditions, in some disease states activation of the CB 2 receptor may enhance or even trigger tissue damage, which will also be discussed alongside the protective actions of the CB 2 receptor stimulation with endocannabinoids or synthetic agonists, and the possible biological mechanisms involved in these effects.

Genomic and Chemical Diversity inCannabis

“…When heated, THCA is converted to delta-9-tetrahydrocannabinol (THC), which has potent psychoactive (Volkow et al, 2014), appetite-stimulating (Berry and Mechoulam, 2002), analgesic (Zogopoulos et al, 2013) and antiemetic (Tram er et al, 2001) effects. These effects are mediated through interactions with human endocannabinoid CB1 receptors found in the brain (Di Marzo et al, 2004), and CB2 receptors, which are concentrated in peripheral tissues (Pacher and Mechoulam, 2011). Other THC receptor binding locations are hypothesized as well (De Petrocellis et al, 2011).…”

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…In summary, the neuronal expression of functional CB2 receptors is still being debated (see Ref. 647 for a comprehensive review) and, possibly as a consequence of this controversy, the role of CB2 in the healthy brain is less characterized than that of the CB1 receptor.…”

Du cannabis aux agonistes sélectifs du récepteur CB2

“…La localisation du CB 2 R expliquerait donc ses fonctions : CB 2 R module la libération des cytokines et la migration des cellules immunitaires et diminue la présentation d'antigènes, ce qui explique l'intérêt thérapeutique grandissant pour cette cible dans diverses pathologies (cancer, douleur, inflammation) [16]. Ces dernières années, l'existence d'un récepteur CB supplémentaire, le GPR55 (G protein-coupled receptor 55), un récepteur couplé aux protéines G orphelin activé par des cannabinoïdes atypiques ne se liant ni au CB 1 R ni au CB 2 [20], la douleur, les cancers, l'ostéoporose ou les maladies du foie par exemple [21]. Dans cette revue, nous n'évoquerons que le potentiel anti-inflammatoire, analgésique et anticancéreux des agonistes sélectifs du CB 2 R.…”