Congenital Gastrointestinal Anomalies in Europe 2010–2019: A Geo-Spatiotemporal and Causal Inferential Study of Epidemiological Patterns in Relationship to Cannabis- and Substance Exposure

Abstract

Introduction: Congenital anomalies (CA’s) of most of the gastrointestinal tract have been linked causally with prenatal or community cannabis exposure. Therefore, we studied this relationship in Europe. Methods: CA data were from Eurocat. Drug-use data were sourced from the European Monitoring Centre for Drugs and Drug Addiction. Income data were taken from the World Bank. Results: When countries with increasing rates of daily cannabis use were compared with those which were not, the overall rate of gastrointestinal CA’s (GCA’s) was higher in the former group (p = 0.0032). The five anomalies which were related to the metrics of cannabis exposure on bivariate analysis were bile duct atresia, Hirschsprungs, digestive disorders, annular pancreas and anorectal stenosis or atresia. The following sequence of GCA’s was significantly linked with cannabis metrics at inverse-probability-weighted-panel modelling, as indicated: esophageal stenosis or atresia, bile duct atresia, small intestinal stenosis or atresia, anorectal stenosis or atresia, Hirschsprungs disease: p = 1.83 × 10−5, 0.0046, 3.55 × 10−12, 7.35 × 10−6 and 2.00 × 10−12, respectively. When this GCA series was considered in geospatial modelling, the GCA’s were significantly cannabis-related from p = 0.0003, N.S., 0.0086, 6.652 × 10−5, 0.0002, 71.4% of 35 E-value estimates and 54.3% minimum E-values (mEVv’s) > 9 (high zone) and 100% and 97.1% > 1.25 (causality threshold). The order of cannabis sensitivity by median mEVv was Hirschsprungs > esophageal atresia > small intestinal atresia > anorectal atresia > bile duct atresia. Conclusions: Seven of eight GCA’s were related to cannabis exposure and fulfilled the quantitative criteria for epidemiologically causal relationships. Penetration of cannabinoids into the community should be carefully scrutinized and controlled to protect against exponential and multigenerational genotoxicity ensuing from multiple cannabinoids.

Perturbation of 3D nuclear architecture, epigenomic dysregulation and aging, and cannabinoid synaptopathy reconfigures conceptualization of cannabinoid pathophysiology: part 1–aging and epigenomics

“…The involvement of key developmental processes Wnt, HoxA, and sonic hedgehog in the above results explains for stroke the implication of cannabinoids in a wide variety of teratogenic, developmental, and neurodevelopmental congenital anomalies, as documented in Colorado, Hawaii, the USA, Canada, Australia, and Europe (27-29, 191-205, 207). This description fits well with the wide variety of congenital anomalies that have been linked with cannabis, including those of the cardiovascular, central nervous, gastrointestinal, chromosomal, limb, uronephrological, body wall, and orofacial systems, as well as in the general embryo (27)(28)(29)(191)(192)(193)(194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204)(205). Congenital anomalies that have been linked to cannabis exposure in the USA were anophthalmia/microphthalmia, anotia/microtia, aortic valve stenosis, atrial septal defect, biliary atresia, bladder extrophy, choanal atresia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, cleft lip with or without cleft palate, cloacal extrophy, club foot, coarctation of the aorta, common truncus, congenital cataract, congenital dislocation of the hip, congenital posterior urethral valve, deletion of 22q11.2, diaphragmatic hernia, Ebstein's anomaly, encephalocele, epispadias, esophageal atresia with or without tracheesophageal atresia, Hirschsprung's disease, congenital megacolon, hydrocephalus without spina bifida, hypospadias, interrupted aortic arch, microcephalus, obstructive genitourinary defect, omphalocele, patent ductus arteriosus, pulmonary valve atresia, pulmonary valve atresia and stenosis, rectal and large intestinal atresia and stenosis, reduction deformity upper limbs, reduction deformity lower limbs, renal agenesis and hypoplasia, small intestinal atresia/stenosis, trisomy 13, trisomy 18, trisomy 21 (Down's syndrome), Turner's syndrome, and ventricular septal defect (192,202,205).…”

“…. Twenty stigmata of aging in cannabis dependence Fifteen hallmarks of aging have been described in cannabis dependence, including (1) increased acute and chronic physical and mental illness (138), (2) acceleration of cardiovascular and organismal age (15), (3) endocrine disruption, particularly of the hypothalamo-pituitary-gonadal axis (139, 140), (4) mitochondrial inhibition (141-144), (5) DNA hypomethylation and advanced epigenetic age (14,(145)(146)(147), ( 6) neuroinflammation accompanying cannabis-associated mental illnesses (148-173), (7) cirrhosis (174-176), (8) degeneration of oocytes and sperm (177,178), (9) increased carcinogenesis (28, [179][180][181][182][183][184][185][186][187][188][189][190], (10) heightened rates of many congenital anomalies and teratologic syndromes (27)(28)(29)(191)(192)(193)(194)(195)(196)(197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207), (11) telomerase inhibition (11,208), (12) chromosomal damage (2,4,8,<...…”

Cannabis- and Substance-Related Carcinogenesis in Europe: A Lagged Causal Inferential Panel Regression Study

“…Reports from the congenital anomaly literature describe the implication of cannabis exposure with various trisomies/monosomies affecting chromosomes 13, 18, 21 and X and this sums up to (113 + 76 + 46 + 153=) 388 megabases or 12.9% of the human genome [ 44 , 45 , 46 , 49 , 50 , 51 , 53 , 57 , 59 , 63 ].…”

“…It is therefore highly relevant that tripling levels of community cannabis exposure have been linked with a tripling of total birth defect rates in Canada’s northern provinces, and increased levels of cannabis exposure have been linked with higher rates of dozens of congenital anomalies in Hawaii, Colorado, Australia and the USA [ 44 , 45 , 46 , 47 , 48 , 49 ], affecting most major organ systems (cardiovascular, gastrointestinal, genitourinary, respiratory, neurological and body wall), including limbs and chromosomal anomalies, trisomies and monosomy [ 44 , 45 , 46 , 47 , 48 , 49 ]. Much data have come to light recently as a result of large studies of national and transnational datasets on this subject [ 44 , 46 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ].…”

Shared and unique 3D genomic features of substance use disorders across multiple cell types

“…The apparent involvement of pancreatic alpha and beta cells in SUDs represents a novel and intriguing insight into their pathology, underscoring the interplay between metabolic regulation and addictive behaviors. Chronic exposure to substances like alcohol, opioids, and cannabinoids can disrupt pancreatic function, leading to dysregulated glucose metabolism and increased risk of metabolic disorders like diabetes [77][78][79]. Chronic alcohol consumption increases risk of pancreatic diseases such as pancreatitis and pancreatic cancer, likely due to the toxic effects of alcohol on pancreatic tissue.…”