One form of Cannabis defense is the up-regulation of cannabinoids and specialized terpenes in response to differing biotic stressors in the environment such as pests and predation. In a study from 2019, tobacco hornworm larvae were fed on an artificial diet of wheat germ containing a cannabis agent. The results showed that on average, significantly high dosages of CBD in the new diet may have decreased survival rates of the larvae. In addition, Maduca sexta larvae avoids eating plants containing high amounts of CBD, allowing for the indication that CBD may be a natural pest deterrent. However, research also has shown when the plant is subjected to mechanical wounds from certain insects, CBD levels were unchanged and even decreased. This observation may be due to difference in the species of insect and chemical secretions, thus providing a new hypothesis that CBD levels vary in response to certain species or even have no effect.
Phytocannabinoid and terpene content in the leaves and flowers of C. sativa rises when under attack by Tetranychus urticae, a common pest for the genus.  When compared to a control of Cannabis sativa without any pest damage, research from 2022 demonstrated an overall increase of secondary metabolites in plants exposed to Tetranychus urtivae infestation and measured this metabolite rise using liquid and gas chromatograph mass spectrometers. The increase was found to be significant, and is attributed as a defense mechanism in the plant.
The induction and up-regulation of cannabinoids as defense genes in Cannabis can be induced by elicitors. In a study from 2019, salicylic acid (SA) was used with GABA as an elicitor to determine its effects on the expression of metabolites involved in THC and CBD biosynthesis. SA and GABA were demonstrated to effectively up-regulate the expression of THCAS, a cannabigerolic acid used to form THC, which resulted in higher levels of THC. These results support the mechanism in which cannabis elicitors such as salicylic acid and GABA triggers a signal cascade for increased expression of defense genes in response to stress.
One line of defense is the release of volatile organic compounds (VOCs) into the air to defend against herbivores by warning neighboring plants. The release of VOCs may begin with the jasmonic (JA) pathway pathway which up-regulates defensive genes. Jasmonic acid, also called jasmonate, is a hormone linked to wound signaling in plants. Rapid wound signaling involves an influx of calcium after the arrival of an action potential. The increase of calcium triggers a regulatory protein, calmodulin, to turn on a protein kinase releasing JASMONATE-ASSOCIATED VQ-MOTIF GENE1 (JAV1) by combining it with phosphoric acid. From a study in 2020, in response to the necrotrophic pathogen gray mold, JA mediated markers were up-regulated in the leaves that were infected, from beginning of infection to the end. Through a series of signals, the plant detects the presence of fungal elicitors/pathogens, then through the JA pathway the expression of defense genes are increased.