Impacts of cannabinoid epigenetics on human development: reflections on Murphy et. al. ‘cannabinoid exposure and altered DNA methylation in rat and human sperm’ epigenetics 2018; 13: 1208-1221.

Abstract

Recent data from the Kollins lab (‘Cannabinoid exposure and altered DNA methylation in rat and human sperm’ Epigenetics 2018; 13: 1208–1221) indicated epigenetic effects of cannabis use on sperm in man parallel those in rats and showed substantial shifts in both hypo- and hyper-DNA methylation with the latter predominating. This provides one likely mechanism for the transgenerational transmission of epigenomic instability with sperm as the vector. It therefore contributes important pathophysiological insights into the probable mechanisms underlying the epidemiology of prenatal cannabis exposure potentially explaining diverse features of cannabis-related teratology including effects on the neuraxis, cardiovasculature, immune stimulation, secondary genomic instability and carcinogenesis related to both adult and pediatric cancers. The potentially inheritable and therefore multigenerational nature of these defects needs to be carefully considered in the light of recent teratological and neurobehavioural trends in diverse jurisdictions such as the USA nationally, Hawaii, Colorado, Canada, France and Australia, particularly relating to mental retardation, age-related morbidity and oncogenesis including inheritable cancerogenesis. Increasing demonstrations that the epigenome can respond directly and in real time and retain memories of environmental exposures of many kinds implies that the genome-epigenome is much more sensitive to environmental toxicants than has been generally realized. Issues of long-term multigenerational inheritance amplify these concerns. Further research particularly on the epigenomic toxicology of many cannabinoids is also required.

Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis

“…The present finding may have arisen either because most of the cardiac defects are higher in high cannabis using areas, or because some of the commoner defects are elevated and these suffice to increase the whole group significantly. This latter was the pattern recently observed in Colorado where atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA) were all found to be dramatically increased in a temporal pattern closely tracking the increased availability of cannabis in that state ( Colorado: Department of Public Health and the Environment, 2018 ; Reece and Hulse, 2019a, 2019c, 2019d ). Moreover, in the most recent Colorado dataset all cardiovascular anomalies have also risen both against time and against cannabis use ( Colorado: Department of Public Health and the Environment, 2018 ; Reece and Hulse, 2019a, 2020a ).…”

“…Both the American Academy of Pediatrics and the American Heart Association have previously issued a position statement which notes increased rates of ventricular septal defect and Ebstein's anomaly in association with cannabis use ( Jenkins et al, 2007 ). Colorado has recently reported a tripling of the rate of atrial septal defect in that state ( Colorado: Department of Public Health and the Environment, 2018 ; Reece and Hulse, 2019a, 2019d ), and indeed atrial septal defect is noted to be more common in cannabis liberal states across USA based on the National Birth Defects Prevention Network publicly available dataset ( National Birth Defects Prevention Network, 2018 ; Reece and Hulse, 2020d ). A large Hawaiian study of over 300,000 births found that hypoplastic left heart, tetralogy of Fallot, pulmonary valve atresia and or stenosis, ventricular septal defect and atrial septal defect were all increased after prenatal cannabis exposure ( Forrester and Merz, 2007 ).…”

“…Now that the commonest class of congenital defects, all cardiovascular defects, have been linked with cannabis use in Hawaii, Colorado and Canada the implications are likely to be very far reaching indeed. The large subject of epigenomics was shown in a recent review to be a particularly important factor in cardiovascular morphogenesis and presumably teratogenesis ( Reece et al, 2018 ; Reece and Hulse, 2019a, 2019c, 2019d ) and was recently shown to widely implicated in cannabinoid molecular and cellular pathways ( Reece and Hulse, 2016 ; Murphy et al, 2018 ; Reece and Hulse, 2019a, 2019c, 2019d ).…”

“…Down's syndrome has been reported in one previously published epidemiological study in association with prenatal cannabis exposure which was in Hawaii ( Forrester and Merz, 2007 ). It was also found to be rising in the Colorado dataset both against time and against cannabis use ( Colorado: Department of Public Health and the Environment, 2018 ; Reece and Hulse, 2019a, 2019c, 2019d ). It was similarly found to be elevated across USA ( Reece and Hulse, 2020d ).…”

America Addresses Two Epidemics – Cannabis and Coronavirus and their Interactions: An Ecological Geospatial Study

“…Cannabinoids are known to interact with the immune system at multiple points including CB1 and CB2 receptors, six vanilloid channels, peroxisome proliferator-activated receptors (PPAR's), serotonin, adenosine, histamine, glycine, sphingosine, dopamine and opioid receptors, three class A orphan G-protein coupled receptors (GPCR's), toll-like receptors, Tcells, B-cells, macrophages and regulatory cells, effects on sodium channels and several types of potassium and calcium channels, modulation of GABA signalling and inhibition of cyclooxygenase and lipoxygenase enzymes, bind directly to mitochondria and cannabinoid receptors also form heterodimers with opioid, adenosine, dopamine, GABA and other GPCR's and have myriad and major epigenetic effects [13][14][15][16][17][18][19][20][33][34][35][36][37][38] .…”