Genotoxicity of heroin and cannabinoids in humans

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

“…Cannabis has been shown to work on developing organisms by a number of complex pathways which have been summarized elsewhere ( Reece et al, 2016 ; Reece and Hulse, 2016 ; Reece, 2018 ; Reece and Hulse, 2019b, 2020b, 2020c ). Briefly stated cannabinoids have been shown to work via: interference with synapse formation by interruption of neurexin / neuroligin scaffolding ( Foldy et al, 2013 ; Anderson et al, 2015 ; Wang, 2016 ); impeding notch signaling ( Lu et al, 2006 ; Newton et al, 2009 ; Tanveer et al, 2012 ; Kim et al, 2014 ) an important morphogen for cardiac, vascular, brain, and hemopoietic tissues ( Carlson, 2014 ); impeding robo/slit signaling with effects on human neocortical exuberant outgrowth, nerve and blood vessel guidance, tissue development in kidney, breast, lung and muscle ( Alpar et al, 2014 ; Blockus and Chedotal, 2016 ), spinal cord midline guidance, several neurodevelopmental disorders including dyslexia ( Galaburda et al, 2006 ) and psychopathy ( Viding et al, 2010 ); impeding axonal guidance by interference with stathmin signaling ( Tortoriello et al, 2014 ); cytoskeletal impairment affecting the actin cytoskeleton ( Wang et al, 2011 ; Miller et al, 2019 ) and microtubule structure and function ( Wang et al, 2011 ; Miller et al, 2019 ); defects on egg and sperm development including gross sperm deformities involving head and tail malformations ( Morishima, 1984 ; Hembree et al, 1999 ; Szutorisz and Hurd, 2016 ; Johnson et al, 2017 ; Murphy et al, 2018 ); impairment of mitochondrial function ( Sarafian et al, 2003 ; Sarafian et al, 2006 ); impairment of sperm mitochondrial function ( Rossato et al, 2005 ); impairment of replacement of sperm histones by protamines ( Chioccarelli et al, 2010 ); epigenetic effects ( Yang et al, 2014 ) and micronucleus effects ( Van Went, 1978 ; Piatti et al, 1989 ; Parolini and Binelli, 2014 ; Reece and Hulse, 2016 ) including cytoplasmic bridges and nuclear blebbing ( Morishima, 1984 ; Huang et al, 1999 ; Russo et al, 2018 ).…”

Cannabis Consumption Patterns Explain the East-West Gradient in Canadian Neural Tube Defect Incidence: An Ecological Study

“…Cannabis has long been known to test positive in the micronuclear assay and this is believed to be on the basis of its interference with microtubular function. [42][43][44] Cannabis also perturbs notch signaling, which is a key morphogen for both embryonic neuraxis and cardiovascular formation. 45,46 Closure of the neural tube initiates at the level of the human hindbrain on post-fertilization day 22 and proceeds bidirectionally cephalad and caudal.…”

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.

“…Cannabis has long been known to test positive in the micronuclear assay due to interference with the function of the mitotic spindle [138][139][140]. This is a major cause of chromosomal disruption and downstream severe genetic damage in surviving cells [141,142], has previously been linked with teratogenesis and carcinogenesis, and which is also potently proinflammatory by releasing dsDNA into the cytoplasm and stimulating cGAS-STING (Cyclic GMP-AMP synthase -STimulator of INterferon Gamma) signalling and downstream innate immune pathways [143][144][145][146].…”