Influence of pyschoactive and nonpsychoactive cannabinoids on cell proliferation and macromolecular biosynthesis in human cells

Epidemiological overview of multidimensional chromosomal and genome toxicity of cannabis exposure in congenital anomalies and cancer development

“…Cannabidiol and cannabidivarin in low doses have been shown to directly oxidize DNA bases which is a highly oncogenic and mutagenic action 97 . Cannabinoids have long been recognized to reduce the synthesis of major macromolecules of life including DNA, RNA proteins and histones 13 , 18 , 60 , 99 – 104 . Reduction in the linker histone H1 has recently been shown to comprise a major oncogenic mechanism by making genes more accessible for transcription 105 .…”

“…Cannabinoid-induced genotoxicity was first demonstrated by researchers in the 1960’s who showed multiple congenital defects developing in prenatally exposed animals 1 – 3 , cannabinoid-induced micronucleus formation from chromosomal mis-segregation errors and mitotic spindle disruption 4 , ring and chain chromosomal malformations in sperm 5 , nuclear blebbing and bridging of oocytes and lymphocytes during cytokinesis 6 , 7 and direct and indirect multimodal mitochondrial toxicities with downstream direct and indirect epigenetic effects 4 , 8 – 12 . It has long been known that cannabinoids reduce histone formation and protamine substitution and synthesis resulting in a more open chromosomal conformation which is more subject to mutagenicity and is also pro-oncogenic as more genes are available for transcription 13 – 18 . Cannabis has a large epigenetic footprint with major alterations of DNA methylation, a change inheritable to subsequent generations in both mice and man 9 , 19 – 26 .…”