Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes

Abstract

Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. that is attracting pharmacological interest because it is non-psychotropic and is abundant in some industrial hemp varieties. The aim of this work was to investigate in parallel the binding properties of CBG to cannabinoid CB1 (CB1R) and CB2 (CB2R) receptors and the effects of the compound on agonist activation of those receptors and of CB1–CB2 heteroreceptor complexes. Using [3H]-CP-55940, CBG competed with low micromolar Ki values the binding to CB1R and CB2R. Homogeneous binding in living cells, which is only technically possible for the CB2R, provided a 152 nM Ki value. Also interesting, CBG competed the binding of [3H]-WIN-55,212-2 to CB2R but not to CB1R (Ki: 2.7 versus >30 μM). The phytocannabinoid modulated signaling mediated by receptors and receptor heteromers even at low concentrations of 0.1–1 μM. cAMP, pERK, β-arrestin recruitment and label-free assays in HEK-293T cells expressing the receptors and treated with endocannabinoids or selective agonists proved that CBG is a partial agonist of CB2R. The action on cells expressing heteromers was similar to that obtained in cells expressing the CB2R. The effect of CBG on CB1R was measurable but the underlying molecular mechanisms remain uncertain. The results indicate that CBG is indeed effective as regulator of endocannabinoid signaling.

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…Cannabigerol is derived from its acidic precursor cannabigerolic acid (CBGA), which also serves as the precursor molecule for the production of THC and CBD. Recently, cannabigerol has attracted more attention for its use in therapeutics due to its lack of intoxicating effects, and more commercial hemp varieties have been developed with CBG and CBGA as the main phytocannabinoids present [139]. As of yet, only a handful of studies have been done to investigate the anti-cancer potential of cannabigerol.…”

Phytocannabinoids: Useful Drugs for the Treatment of Obesity? Special Focus on Cannabidiol

“…Cannabis plants produce cannabigerolic acid (CBGA), which is a direct precursor of cannabinoids: 9 -THC, CBC and CBD (44,45). Preliminary studies, using plasma membranes isolated from the CHO and HEK-293 cells expressing human CB 1 and CB 2 receptors, have shown that CBG acts as a partial agonist of both cannabinoid receptors (46). Similarly to other phytocannabinoids CBG has an ability to interact with endocannabinoidome receptors, such as TRPV1, 2, TRPA1, and TRPM8 channels (26).…”

Cannabinoids in the Pathophysiology of Skin Inflammation

“…The cutaneous ECS is involved in skin differentiation, proliferation, and survival through the actions of AEA and 2-AG that are produced in various skin structures and modulate multiple functions of the skin and its appendages, including hair growth, maintaining the skin barrier integrity, immune response, and the processing of sensory input such as pruritus and pain [69][70][71][72]. Table 1 summarizes cannabinoid types, classes, and their receptor interactions [73][74][75][76][77][78][79][80][81][82][83].…”