Influence of psychoactive and nonpsychoactive cannabinoids on chromatin structure and function in human cells

Cannabinoid and substance relationships of European congenital anomaly patterns: a space-time panel regression and causal inferential study

“…It has been shown both in classical focussed investigations of histone synthesis [ 28–30 , 41 , 168 , 169 ] and of proteomic screens [ 40 ] that histone synthesis in cannabis-exposed tissues is greatly reduced, sometimes by as much as 50%. This has far-reaching implications for epigenomic dysregulation but remains relatively unexplored by modern methods.…”

“…Cannabis-induced changes to histone phosphorylation and acetylation states have also previously been documented [ 41 ]. The serious changes induced in sperm motility by altered tubulin glycosylation have also recently been documented and were alluded to above as part of the important ‘tubulin code’ [ 42 ].…”

“…Several studies have also shown cannabis to have a major effect perturbing DNA methylation [ 31–37 ], with these changes shown to be inheritable to subsequent generations [ 31–37 ], to perturb DNA methylation in the nucleus accumbens of offspring and affect behaviour [ 33 , 34 ], to be seen in human sperm [ 31 , 32 ] and to improve in both rats and humans after cessation of cannabis exposure [ 32 ]. Cannabis has an adverse effect on protein synthesis including histone formation, a change which necessarily opens up chromatin for aberrant gene expression [ 40 , 41 ]. Thus cannabinoids derange the ‘histone code’.…”

Cannabinoid exposure as a major driver of pediatric acute lymphoid Leukaemia rates across the USA: combined geospatial, multiple imputation and causal inference study

“…Cannabinoids themselves carry a large epigenomic footprint. THC has been shown to reduce the level of synthesis of nuclear histones, sometimes by half [ 84 , 85 ]. Marked epigenomically-mediated reduction of brain D2-dopamine receptors has been demonstrated in F1 rodent offspring following PCE [ 86 ].…”

European Epidemiological Patterns of Cannabis- and Substance-Related Body Wall Congenital Anomalies: Geospatiotemporal and Causal Inferential Study

“…Multiple pathways to cannabinoid genotoxicity have been described, some of them for many decades, including the induction of severe dysmorphology of sperm [ 20 , 21 ]; the severe inhibition of oocyte division [ 22 ]; single- and double-stranded DNA breaks; chromosomal breakages [ 23 , 24 , 25 ]; and end-to-end fusions, including ring and chain translocations [ 21 ]; the oxidation of DNA bases [ 23 ]; interference with sperm histone-protamine exchange [ 26 ]; the inhibition of oviduct function [ 27 ]; the inhibition of Sertoli cell function [ 27 ]; the reduction in DNA, RNA, and protein synthesis [ 28 , 29 , 30 , 31 , 32 , 33 ]; the alteration of DNA methylation patterns [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]; the reduction in histone synthesis [ 26 ]; the reduction in phospho- and acetylated-activated histone production [ 29 , 30 , 43 ]; and the heritable passage of altered patterns of DNA and histone expression to subsequent generations [ 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 44 ].…”