Medical Cannabis augments neutrophil functions and bacterial killing by inducing neutrophil extracellular traps

Cannabis has now long been used by cancer patients as a natural palliative treatment for chemotherapy and anti-cancer-related side effects. Cannabis consummation has beneficial alleviate effects on nausea, pain, loss of sleep, and appetite, improving many aspects of patient quality of life. On the other hand, cannabis consumption shows potent immunoregulatory properties which modulate the immune system in numerous clinical trials, when its full impact on the immune system is far from been elucidated. Here, we unveiled the properties of cannabis as a dominant molecule that amplifies many arms of neutrophil anti-microbial effector function as a potent neutrophil activator. We show that extracts of CBD-rich cannabis strains enhance neutrophil extracellular trap (NET’s or NETosis), augmenting both the overall amount of NETotic cells and NET’s area. CBD-rich cannabis extracts lead to neutrophils intracellular signaling involving mTORC1, JNK, RSK-1, MAPK/ERK kinase pathway activation, enhanced ROS production, and rapid deployment of extracellular DNA in cannabinoid receptors or THC/CBD independent pathway. Such enhancement of neutrophils effector functions results in killing twice more bacteria than uninduced neutrophils from healthy donors. The addition of DNAse-1, which digest the extracellular chromatin NET’s, effectively abrogates the cannabis-associated NETosis and abolishes the cannabis-mediated enhanced bacterial killing by neutrophils. Nonetheless, since NETosis is implicated in cancer progression when cancer cells abuse NETosis to escape host immune surveillance, evade immunotherapy, mediate metastasis, awaken dormant cancer cells, or promote thrombosis, its consumption needs to be carefully considered in patients when malignancy is diagnosed.