Cannabinoidomics – An Analytical Tool to Understand the Effect of Medical Cannabis Treatment in Clinical and Pre-clinical Studies

Paula Berman, Biology, Technion - Israel Institute of Technology, Haifa, Israel (bermansh@gmail.com)
Liron Sulimani, Cannasoul Analytics, Caesarea, Israel
Anat Gelfand, Biology, Technion - Israel Institute of Technology, Haifa, Israel
Keren Amsalem, Biology, Technion - Israel Institute of Technology, Haifa, Israel
Gil Lewitus, Biology, Technion - Israel Institute of Technology, Haifa, Israel
David Meiri, Biology, Technion - Israel Institute of Technology, Haifa, Israel

Cannabis is a complex plant composed of several hundred compounds of various chemical classes and wide concentrations. Among these, phytocannabinoids, the natural cannabinoids found in Cannabis, are unique to this plant. Their biological mechanisms of action are attributable mainly to their interactions with the endocannabinoid system (ECS), either by activating/inhibiting cannabinoid and non-cannabinoid receptors, metabolic (biosynthesizing or degrading) endocannabinoid enzymes and/or fatty acid binding proteins. In order to study the pharmacological effects of whole Cannabis extracts on the endocannabinoid metabolome we have developed an accurate high-resolution liquid chromatography-mass spectrometry (HR-LC-MS/MS) tool for identification and quantification of endocannabinoids and other endogenous cannabimimetic lipids, phytocannabinoids, and their metabolites in various biological matrices.

In this study, identification of target compounds by HR-LC-MS/MS was performed according to the retention times and MS/MS fragmentation patterns of available analytical standards as a reference for the identification of additional compounds from all subclasses. Overall, we identified (a) over 90 different phytocannabinoids from all 10 different phytocannabinoid subclasses by screening various natural and decarboxylated Cannabis flowers; (b) over 90 endocannabinoids and cannabimimetic lipids from 20 different lipid families by screening mice serum and tissues (brain, liver and spleen); and (c) 20 (-)-Δ9-trans-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) metabolites in mice serum and liver samples following treatment with Cannabis extracts. Extraction methods were then developed and validated for quantifying the identified compounds in various biological fluids, tissues, and cells. This cannabinoidomic tool can be used to accurately determine changes in the levels of endocannabinoid metabolites as a result of Cannabis treatment for diverse physiological and pathological conditions.

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Abstract Reference & Short Personal Biography of Presenting Author

Paula has a BSc in Biotechnology Engineering, and MSc and PhD in Environmental Engineering, all from Ben Gurion University of the Negev in Israel. For the last three years Paula has been working as a postdoctoral fellow at the Laboratory of Cancer Biology and Cannabinoid Research in the Technion - Israel Institute of Technology (advisor: Prof. David Meiri). Paula's research involves the development of LC/MS/MS methods to study the effects of Cannabis on the endocannabinoid metabolome by means of “cannabinoidomics” (phytocannabinoid and endocannabinoid “omics”).