Could cannabinoids reshape melanoma treatment through the microbiome?

Despite advances in targeted and immunotherapy for melanoma, resistance to treatment and severe adverse effects pose significant challenges. This necessitates the development of new treatment strategies, and cannabinoids, because of the extensive preclinical evidence for their cytotoxic action on carcinoma cells in a variety of cancers, can offer a novel therapeutic option when used appropriately. Indeed, the potential therapeutic benefits of cannabinoids were formally recognized in the world and much more recently in the United Kingdom when cannabis-based medicinal products were moved from Schedule 1 of the Misuse of Drugs Regulations 2001 to Schedule 2 in 2018. This move further encouraged scientists to look at more applications of cannabinoids in different disorders. Although the potential psychoactivity of cannabis as a Schedule 1 drug hinders research, more research could focus on non-psychoactive components such as cannabidiol (CBD) and cannabigerol (CBG). This review summarizes some past and current research on the relationship between the cannabinoid system and the microbiome in patients with metastatic melanoma who undergo immunotherapy. The review also provides a comprehensive background on the function of the cannabinoid system in normal and diseased skin, as well as future directions in using cannabinoids as an adjunct to chemotherapeutics in the treatment of the disease.