Cannabinomics: Application of Metabolomics in Cannabis (Cannabis sativa L.) Research and Development

Abstract

Cannabis (Cannabis sativa L.) is a complex, polymorphic plant species, which produces a vast array of bioactive metabolites, the two major chemical groups being cannabinoids and terpenoids. Nonetheless, the psychoactive cannabinoid tetrahydrocannabinol (Δ ⁹ -THC) and the non-psychoactive cannabidiol (CBD), are the two major cannabinoids that have monopolized the research interest. Currently, more than 600 Cannabis varieties are commercially available, providing access to a multitude of potent extracts with complex compositions, whose genetics are largely inconclusive. Recently introduced legislation on Cannabis cultivation in many countries represents a great opportunity, but at the same time, a great challenge for Cannabis research and development (R&D) toward applications in the pharmaceutical, food, cosmetics, and agrochemical industries. Based on its versatility and unique capabilities in the deconvolution of the metabolite composition of complex matrices, metabolomics represents an ideal bioanalytical tool that could greatly assist and accelerate Cannabis R&D. Among others, Cannabis metabolomics or cannabinomics can be applied in the taxonomy of Cannabis varieties in chemovars, the research on the discovery and assessment of new Cannabis-based sources of bioactivity in medicine, the development of new food products, and the optimization of its cultivation, aiming for improvements in yield and potency. Although Cannabis research is still in its infancy, it is highly foreseen that the employment of advanced metabolomics will provide insights that could assist the sector to face the aforementioned challenges. Within this context, here, the current state-of-the-art and conceptual aspects of cannabinomics are presented.

Keywords: cannabinoids; cannabis terpenoids; chemovars; drug discovery; medicinal cannabis; plant chemotaxonomy; plant metabolomics.

FIGURE 1

Cannabis sativa L.; One-week old seedling of the hemp dioecious strain “Finola” (A), 4 weeks old plant of the strain “BIK” (B), and plants at the flowering stage (C). Close up photo of a flower of the strain “Skunk” (D), and big capitate-sessile trichomes as shown in the stereomicroscope (E).

FIGURE 2

Publications grouped in various disciplines including the term “cannabis” (A) and the corresponding total number of publications (B), and the number of citations acquiring for the terms “cannabis” and “metabolomics” (C). Data were acquired from the data base of the ISI Web of Science (Clarivate Analytics, Philadelphia, PA, United States).

FIGURE 3

Chemical structures of major Cannabis (Cannabis sativa L.) cannabinoids.

FIGURE 4

Biosynthesis of Cannabis (Cannabis sativa L.) mono-, sesqui, and triterpenoids.

FIGURE 5

Biosynthetic pathway of Cannabis (Cannabis sativa L.) cannabinoids.

FIGURE 6

GC/EI/MS (A) total ion chromatograms of Cannabis sativa L. var Finola flower extracts. Approximately 220 metabolite features were discovered and (B) Cellular overview of the metabolite composition of Cannabis using the Plantcyc tools (Karp et al., 2009; Caspi et al., 2015).

FIGURE 7

Conceptual pipeline of the biomarker-assisted selection of Cannabis (Cannabis sativa L.) chemovars based on the desired traits, performing metabolomics