Charting the Cannabis plant chemical space with computational metabolomics

Introduction: The chemical classification of Cannabis is typically confined to the cannabinoid content, whilst Cannabis encompasses diverse chemical classes that vary in abundance among all its varieties. Hence, neglecting other chemical classes within Cannabis strains results in a restricted and biased comprehension of elements that may contribute to chemical intricacy and the resultant medicinal qualities of the plant. Objectives: Thus, herein, we report a computational metabolomics study to elucidate the Cannabis metabolic map beyond the cannabinoids. Methods: Mass spectrometry-based computational tools were used to mine and evaluate the methanolic leaf and flower extracts of two Cannabis cultivars: Amnesia haze (AMNH) and Royal dutch cheese (RDC). Results: The results revealed the presence of different chemical compound classes including cannabinoids, but extending it to flavonoids and phospholipids at varying distributions across the cultivar plant tissues, where the phenylpropnoid superclass was more abundant in the leaves than in the flowers. Therefore, the two cultivars were differentiated based on the overall chemical content of their plant tissues where AMNH was observed to be more dominant in the flavonoid content while RDC was more dominant in the lipid-like molecules. Additionally, in silico molecular docking studies in combination with biological assay studies indicated the potentially differing anti-cancer properties of the two cultivars resulting from the elucidated chemical profiles. Conclusion: These findings highlight distinctive chemical profiles beyond cannabinoids in Cannabis strains. This novel mapping of the metabolomic landscape of Cannabis provides actionable insights into plant biochemistry and justifies selecting certain varieties for medicinal use.