Integrating analytical methods for endocannabinoid system exploration: Determination of endogenous and plant cannabinoids in relevant matrices

A growing body of evidence highlights the relevance of the endocannabinoid system (ECS) in various physiological and disease states [1]. Phytocannabinoids, notably Δ9-tetrahydrocannabinol (Δ9-THC) were firstly studied to investigate mechanisms of action associated with Cannabis sativa L., their prolific natural source. Such biological effects were attributed to the modulation of the ECS, which was found to be subject to pleiotropic signaling by endogenous ligands, referred to as endocannabinoids. The complex role of this system and related molecules in different biological substrates is yet to be elucidated. In view of this, reliable determination of both endo- and phytocannabinoids is of crucial importance, considering the various analytical challenges involved.

In this work, efficient chromatographic methods were developed and validated in physiologically relevant matrices, providing required performance characteristics in terms of sensitivity and cost-effectiveness. Liquid chromatography high-resolution mass spectrometry (LC-HRMS) was employed for identification and quantification of major endocannabinoids 1-AG, 2-AG and anandamide in biological samples. With respect to C. sativa biomass, major bioactive cannabinoids such as Δ9-THC, CBD and their biogenetic precursors THCA, and CBDA were determined using an optimized UPLC-PDA methodology. Both approaches effectively overcome the well-reported limitations [2] associated with separation and stability of the studied compounds, through optimized protocols for sample preparation and analysis. It is envisioned that the developed integrated approach will enable further exploration of the ECS and ultimately drive therapeutic interventions based on this multifaceted system.

The authors declare no conflict of interest; Funding: CANNABinAutism (ERDF & Greek National Funds, ID: Τ2ΕΔΚ-02 075).

Publikationsverlauf

Artikel online veröffentlicht:
12. Dezember 2022

• References

• 1 di Marzo V. New approaches and challenges to targeting the endocannabinoid system. Nature Reviews Drug Discovery 2018; 17: 623-639
• 2 Berman P, Sulimani L, Gelfand A. et al. Cannabinoidomics – An analytical approach to understand the effect of medical Cannabis treatment on the endocannabinoid metabolome. Talanta 2020; 219: 121336