Dorin Harpaz  ^_ Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel; Department of Postharvest Science, Institute of Postharvest and Food Sciences, The Volcani Center, Agricultural Research Organization, Bet Dagan, 50250, Israel.
Boris Veltman  ^_ Institute of Biochemistry, Food Science and Nutrition, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel; Department of Postharvest Science, Institute of Postharvest and Food Sciences, The Volcani Center, Agricultural Research Organization, Bet Dagan, 50250, Israel.
 Yael Sadeh  ^_ Institute of Soil Water and Environmental Sciences, Volcani Center, Agricultural Research Organization, POBox 6, Bet-Dagan, 50250, Israel.
Robert S Marks  ^_ Department of Biotechnology Engineering, Faculty of Engineering Science, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel; National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel; The Ilse Katz Center for Meso and Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel.
Nirit Bernstein  ^_ Institute of Soil Water and Environmental Sciences, Volcani Center, Agricultural Research Organization, POBox 6, Bet-Dagan, 50250, Israel. 
Evgeni Eltzov  ^_ Department of Postharvest Science, Institute of Postharvest and Food Sciences, The Volcani Center, Agricultural Research Organization, Bet Dagan, 50250, Israel.

The world acceptance of medical cannabis slowly widens. Cannabinoids are known as the main therapeutic active compounds in the cannabis plant, yet their bioactive physiological effects are still unknown. In this study, the mode of action of nine selected cannabinoids was examined using a bioluminescent bacterial panel, as well as the extracts of six different cannabis varieties and cannabinoids standards artificial mixtures. The bacterial panel was composed of genetically modified E. coli bacteria that is commonly found in the gut microbiome, to which a lux operon was added to various stress promoters. The panel was exposed to the cannabinoids in order to identify bacterial defense mechanism, via the aforementioned specific stress types response. This enables the understanding of the toxicity mode of action of cannabinoids. From all the tested cannabinoids, only delta-9-tetrahydrocannabinol (THC) and delta-9-tetrahydrocannabinolic acid A (THCA) produced a genotoxic effect, while the other tested cannabinoids, demonstrated cytotoxic or oxidative damages. Unlike pure cannabinoids, cannabis plant extracts exhibited mostly genotoxicity, with minor cytotoxicity or oxidative stress responses. Moreover, cannabinoids standards artificial mixtures produced a different response patterns compared to their individual effects, which may be due to additional synergistic or antagonistic reactions between the mixed chemicals on the bacterial panel. The results showed that despite the lack of cannabigerol (CBG), cannabidivarin (CBDV), cannabinol (CBN), and cannabichromene (CBC) in the artificial solution mimicking the CN6 cannabis variety, a similar response pattern to the cannabinoids standards mixture was obtained. This work contributes to the understanding of such correlations and may provide a realistic view of cannabinoid effects on the human microbiome.