International Multi-Centre Research suggests that Cannabidiol could be a Modulator of Endocannabinoid Signalling

Binding and signalling studies reveal cannabinoid a potential allosteric site for cannabidiol in type-2 cannabinoid receptors

Cordoba, Spain – November 17, 2017 – Recent evidence presents the endocannabinoid system as one of the most relevant in mammals for homeostatic control of energy expenditure and temperature, and for regulating innate and acquired immunity and neural transmission.

Phytoplant Research S.L participated on a first-of-its-kind collaborative study to explore the possibility that the cannabis-derived molecule, cannabidiol (CBD), acts as an allosteric ligand of type-2 cannabinoid receptors (CB2) by checking its ability to modulate the binding and functional effect of CB2 agonists. In fact, allosteric modulators can impact both on the affinity of the orthosteric binding pocket and in the intracellular signalling responses, in either a positive or negative direction. 

Results arising from this study indicate that CBD acts as a negative modulator of the CB2 receptors, probably acting at an allosteric site. CBD at nanomolar levels was able to modify the binding and the activation of the CB2 agonists without acting at the orthosteric site of the receptor. The effect of a selective CB2 agonist was modulated by CBD at physiologically relevant (nanomolar) concentrations. 

The participation of a third component, acting as a mediator of CBD effects on CB2 signalling cannot be ruled out. In the absence of consensus data showing a direct interaction between CBD and cannabinoid receptors, only indirect evidence suggests that CBD could be a modulator of endocannabinoid signalling. Further experimental effort is needed to identify common motives for endocannabinoid action on ligand-gated and G-protein-coupled receptors (GPCRs), or to identify molecules interacting with these receptors and acting as mediators of the allosteric-like effect disclosed by CBD. 

The Laboratory of Molecular Neurobiology of the University of Barcelona, headed by Rafael Franco in Europe, pioneered the research on the biochemical, pharmacological and functional aspects of GPCRs such as cannabinoid receptors. Significant advances have been achieved in those aspects and also on the expression and differential function of cannabinoid receptors in neurodegeneration. One of the main achievements is the identification of those receptors as targets of diseases affecting the central nervous system (CNS) and the design and proposal of novel therapeutic drugs.

“We are very glad to be deciphering the health benefits of the components of Cannabis sativa while remembering how in the 70's my grandfather used his hands to build hemp shoe soles,” said Prof. Rafael Franco of the Department of Biochemistry and Molecular Biomedicine of the University of Barcelona.

“It is essential to understand in-depth the mechanism of action of these compounds that may imply an improvement in the health and well-being of the population. This is important in those cases in which the treatment with a compound “gifted” by nature could improve fundamental aspects of a patient’s quality of life,” said Dr. Carlos Ferreiro Vera, manager of the analytical Department at Phytoplant Research S.L.

Finding binding motives for CBD in cannabinoid receptors or other, non-GPCR, CBD targets could help in understanding some of the actions reported for endocannabinoids and for natural cannabinoids such as Δ9-tetrahydrocannabinol (THC)and CBD. GPCRs constitute the target of 40–45% of current medicines that act, as agonists or antagonists, via the orthosteric centre. The discovery of GPCR allosteric modulators or of modulators of signalling at concentrations 1–2 orders of magnitude below the IC50 values obtained in competing with the binding of orthosteric compounds, would open new perspectives for therapeutic benefit.

About The University of Barcelona:

The Laboratory of Molecular Neurobiology headed by Prof. Rafael Franco belongs to the Department of Biochemistry and Molecular Biomedicine of the University of Barcelona, which is the Spanish Institution with the highest score in research rankings. Its research is devoted to decipher the structure and function of GPCRs and their heteroreceptor complexes, with the aim of identifying therapeutic targets to combat neurodegenerative diseases, especially Parkinson’s and Alzheimer’s diseases.  Among the different GPCRs under scrutiny, cannabinoid receptors offer unique challenges due to the lipid nature of endocannabinoids. Using a myriad of technological approaches the laboratory has been able to uncover allosteric sites in those receptors that may explain some of therapeutic-like effects of cannabis components.

Media Contact:

Name: Rafael Franco

Phone: 610 30 61 23

Email: rfranco@ub.edu

About The University of Ferrara:

The Laboratory of Cellular and Molecular Pharmacology of the University of Ferrara, directed by Prof. Katia Varani, focuses its research on the ligand-receptor interaction. The research group is committed to the identification of novel pharmacological targets involved in different pathologies such as neurodegenerative disorders, chronic inflammatory diseases, ischemia and cancer. The laboratory has at its disposal the most advanced instruments for the study of the cellular and molecular pathogenic mechanisms and their modulation by means of a receptor-based approach. From several years, the research group is also specialized in binding and functional studies aimed to the evaluation of the affinity, selectivity and potency of novel potential ligands, in particular in the G-protein coupled receptor field.

About The University of Oviedo:

Dr. Eva Martínez-Pinilla, a former postdoc in the Molecular and Cell Neurobiology group in CIMA (Pamplona, Spain) is now integrated in the Aging Brain and Neurodegenerative Diseases group (GECYEN) directed by Prof. J. Tolivia in the Neurosciences and Health Research Institutes (INEUROPA/ISPA) of the Principality of Asturias (ISPA) at the University of Oviedo. The research interest of the group focuses on the study of the central nervous system, from the normal cytoarchitectonic characteristics in various mammals, including humans, to the modifications caused by normal aging. The laboratory also focuses on the effects on neural homeostasis induced by neurodegenerative diseases. One of the aspects under scrutiny is the expression of Apolipoproteins in normal aging and in neurodegenerative conditions. The overall aim is to look for targets to afford neuroprotection. In this sense, the development of new drugs and the knowledge of their mechanism of action are fundamental in the fight against neurodegenerative diseases.

About Phytoplant Research S.L:

Phytoplant Research S.L. is a privately owned Spanish company founded in 2008 and active in the field of phytotherapy research. It specializes in developing the industrial chain of medicinal plants, from selection and breeding to registration, cultivation of registered varieties and obtaining derived products. The company focuses on R&D products that contain plant material and extracts, as well as essential and seed oils. These products represent significant economic potential for the pharmaceutical, nutraceutical and dermocosmetic industries. They also ensure the industrial supply of phyto-pharmaceutical quality raw materials through the cultivation of medicinal plants and extraction of plant material, with the objective of isolating, purifying and manufacturing naturally active ingredients (psychotropic and non-psychotropic), semi-synthetic, biotransformed, pharmaceutically acceptable salts and derivatives.

Media Contact:

Name: Stefan Martin Meyer

Phone: (0034) 957 10 16 29

Email: media@phytoplant.es