C. elegans as a test system to study relevant compounds that contribute to the specific health-related effects of different cannabis varieties

Abstract

The medicinal effects of cannabis varieties on the market cannot be explained solely by the presence of the major cannabinoids Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD). Evidence for putative entourage effects caused by other compounds present in cannabis is hard to obtain due to the subjective nature of patient experience data. Caenorhabditis elegans (C. elegans) is an objective test system to identify cannabis compounds involved in claimed health and entourage effects. From a medicinal cannabis breeding program by MariPharm BV, the Netherlands a set of 12 varieties were selected both THC rich varieties as well as CBD rich varieties. A consecutive extraction process was applied resulting in a non-polar (cannabinoid-rich) and polar (cannabinoid-poor) extract of each variety. The test model C. elegans was exposed to these extracts in a broad set of bioassays for appetite control, body oscillation, motility, and nervous system function. Exposing C. elegans to extracts with a high concentration of cannabinoids (> 1 μg/mL) reduces the life span of C. elegans dramatically. Exposing the nematodes to the low-cannabinoid (< 0.005 μg/mL) polar extracts, however, resulted in significant effects with respect to appetite control, body oscillation, motility, and nervous system-related functions in a dose-dependent and variety-dependent manner. C. elegans is a small, transparent organism with a complete nervous system, behavior and is due to its genetic robustness and short life cycle highly suitable to unravel entourage effects of Cannabis compounds. Although C. elegans lacks an obvious CB1 and CB2 receptor it has orthologs of Serotonin and Vanilloid receptor which are also involved in (endo)cannabinoid signaling. By using C. elegans, we were able to objectively distinguish different effects of different varieties despite the cannabinoid content. C. elegans seems a useful test system for studying entourage effects, for targeted medicinal cannabis breeding programs and product development.