Minor cannabinoid major impact: Role of varins in cannabis aphid resistance

Plants protect themselves from threats by generating numerous toxic secondary metabolites. This leads to insect herbivores to respond by developing counter-adaptations to these metabolites. Hemp (Cannabis sativa) is known for having a multitude of secondary metabolites including cannabinoids. The two most well-known cannabinoids in hemp are Tetrahydrocannabinol (THC) and cannabidiol (CBD), but there are more than 100 other cannabinoids known. These cannabinoids have natural variation levels in different Cannabis genotypes. The evolutionary development of cannabinoids is believed to be a novel herbivory defense adaptation. Here we investigated the role of a minor cannabinoid that is naturally less abundant, cannabidivarinic acid (CBDVA). CBDVA is part of the varin series of cannabinoids and has a shorter carbon side chain but follows the same synthesis pathway as most cannabinoids. Cannabis aphid performance was studied on different lines of hemp (high and low CBDVA) and aphids performed significantly better low CBDVA hemp compared to the high CBDVA hemp. In contrast to positive effects observed after CBD supplementation in artificial diets, supplementation of CBDVA in artificial diets decreased cannabis aphid survival and fecundity. This negative trend of CBDVA supplementation was also observed in aphids not adopted to hemp. The negative impacts observed by CBDVA indicate that cannabis aphids have adapted to some but not all cannabinoids and less prominent cannabinoids need further investigation as potential insecticides.