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Effects of Cannabigerol Revealed for the First Time

Published: Jun 25, 2018   
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Phytoplant Research participated in a first-ever pioneering collaborative project to investigate the ability of cannabinoid cannabigerol (CBG), the molecular precursor of Δ9-tetrahydrocannabinol (Δ 9-THC) and cannabidiol (CBD). The study investigated the ability of the above to modulate the affinity and functionality of type-1 and type-2 cannabinoid receptors (CB1 and CB2, respectively) and CB1–CB2heteroreceptor complexes. It concluded that CBG significantly modulates CB2R- and CB1R/CB2R-mediated endocannabinoid action, while the effects are weak in CB1R-expressing cells.

The results of this research, published in the journal Frontiers in Pharmacology, show that CBG, a non-psychotropic phytocannabinoid, at nanomolar concentrations, is capable of acting as a competitive partial agonist of the CB2R. Regarding its action on CB1R, it is not possible to rule out a potential allosteric action, since the blocking of intracellular signalling of CB1R agonists occurs at concentrations of CBG lower than those necessary for its binding to the orthostatic site of the receptor.

These findings reopen the discussion about the ability of other phytocannabinoids, whose mechanism of action was unknown, to bind directly to cannabinoid receptors as Δ 9-THC does. In the study, researchers obtained results using different approaches that include the classic radioligand ligand binding, new fluorescent-based binding techniques and the measurement of signalling pathways. In these assays, CBG was able to modify the affinity and activity of selective CB1R and CB2R agonists at concentrations with physiological relevance (nanomolar).

The results also suggest that the partial agonism on the CB2R is regulated by the presence of the CB1R. However, more complex alternative scenarios cannot be ruled out as CBG may act on the orthosteric site of the CB1R protomer and as protean agonist of the CB1R protomer within the CB1R/CB2R heteromer.

The Molecular Neurobiology Laboratory at the University of Barcelona, directed by Rafael Franco, is a pioneer in Europein the research of the biochemical, pharmacological and functional aspects of G protein-coupled receptors (GPCRs), including cannabinoid receptors, as well as the expression and differential function of cannabinoid receptors during neurodegeneration. One of its main achievements has been the characterization of these receptors as possible therapeutic targets for the design and development of new drugs to treat diseases that affect the central nervous system.

"Natural compounds present in Cannabis sativa L. and acting on cannabinoid receptors are guiding the search for novel drugs to combat neurodegenerative diseases," said Professor Rafael Franco of the Department of Biochemistry and Molecular Biomedicine of the University of Barcelona.

"With these findings, we demonstrate clearly that CBG is active at the cannabinoid receptors CB1 and CB2 and that it exerts its effects through those receptors. We have deepened the knowledge about phytocannabinoids and reopened the discussion about the interaction between the Cannabis plant compounds," said Dr. Xavier Nadal, Director of the R & D -  Extraction Department at Phytoplant Research S.L.      

The results of the study indicate that CBG is indeed effective as a regulator of endocannabinoid signalling and may exert beneficial actions with therapeutic potential via cannabinoid receptors.

This article has been republished from materials provided by Phytoplant Research. Note: material may have been edited for length and content. For further information, please contact the cited source.


Navarro, G., Varani, K., Reyes-Resina, I., Sánchez de Medina, V., Rivas-Santisteban, R., Sanchez-Carnerero Callado, C., ... & Borea, P. A. (2018). Cannabigerol action at cannabinoid CB1 and CB2 receptors and at CB1-CB2 heteroreceptor complexes. Frontiers in Pharmacology, 9, 632.


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