Novel Insights into Potential Cannabis-Related Cancerogenesis from Recent Key Whole Epigenome Screen of Cannabis Dependence and Withdrawal: Epidemiological Commentary and Explication of Schrott et al.

Whilst the cannabis-cancer link has been traditionally described as controversial recent whole nation and whole continent studies have demonstrated that well documented laboratory-based multimodal cannabinoid genotoxicity is indeed reflected in numerous cancer types in larger epidemiological series. A recent longitudinal human sperm epigenome-wide DNA methylation screen in both cannabis dependence and cannabis withdrawal has revealed remarkable insights into the manner in which widespread perturbations of DNA methylation may lead to cancerogenic changes in both the exposed and subsequent generations as a result of both cannabis exposure and withdrawal. These results therefore powerfully strengthen and further robustify the causal nature of the relationship between cannabinoid exposure and cancerous outcomes well beyond the previously published extensive mechanistic literature on cannabinoid genotoxicity. The reported epigenomic results are strongly hypothesis generating and call powerfully for further work to investigate oncogenic mechanisms in many tissues, organs and preclinical models. These epigenomic results provide an extraordinarily close predictive account for the epidemiologically observed pattern of cannabis-related malignant disease and indicate that malignant and multigenerational cannabinoid epigenotoxicity is potentially a significant and major public health concern.