{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T22:08:15Z","timestamp":1778882895393,"version":"3.51.4"},"reference-count":175,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Reports"],"abstract":"<jats:p>Introduction: Recent series of congenital anomaly (CA) rates (CARs) have showed the close and epidemiologically causal relationship of cannabis exposure to many CARs. We investigated these trends in Europe where similar trends have occurred. Methods: CARs from EUROCAT. Drug use from European Monitoring Centre for Drugs and Drug Addiction. Income data from World Bank. Results: CARs were higher in countries with increasing daily use overall (p = 9.99 \u00d7 10\u221214, minimum E-value (mEV) = 2.09) and especially for maternal infections, situs inversus, teratogenic syndromes and VACTERL syndrome (p = 1.49 \u00d7 10\u221215, mEV = 3.04). In inverse probability weighted panel regression models the series of anomalies: all anomalies, VACTERL, foetal alcohol syndrome, situs inversus (SI), lateralization (L), and teratogenic syndromes (TS; AAVFASSILTS) had cannabis metric p-values from: p &lt; 2.2 \u00d7 10\u221216, 1.52 \u00d7 10\u221212, 1.44 \u00d7 10\u221213, 1.88 \u00d7 10\u22127, 7.39 \u00d7 10\u22126 and &lt;2.2 \u00d7 10\u221216. In a series of spatiotemporal models this anomaly series had cannabis metric p-values from: 8.96 \u00d7 10\u22126, 6.56 \u00d7 10\u22126, 0.0004, 0.0019, 0.0006, 5.65 \u00d7 10\u22125. Considering E-values, the cannabis effect size order was VACTERL &gt; situs inversus &gt; teratogenic syndromes &gt; FAS &gt; lateralization syndromes &gt; all anomalies. 50\/64 (78.1%) E-value estimates and 42\/64 (65.6%) mEVs &gt; 9. Daily cannabis use was the strongest predictor for all anomalies. Conclusion: Data confirmed laboratory, preclinical and recent epidemiological studies from Canada, Australia, Hawaii, Colorado and USA for teratological links between cannabis exposure and AAVFASSILTS anomalies, fulfilled epidemiological criteria for causality and underscored importance of cannabis teratogenicity. VACTERL data are consistent with causation via cannabis-induced Sonic Hedgehog inhibition. TS data suggest cannabinoid contribution. SI&amp;L data are consistent with results for cardiovascular CAs. Overall, these data show that cannabis is linked across space and time and in a manner which fulfills epidemiological criteria for causality not only with many CAs, but with several multiorgan teratologic syndromes. The major clinical implication of these results is that access to cannabinoids should be tightly restricted in the interests of safeguarding the community\u2019s genetic heritage to protect and preserve coming generations, as is done for all other major genotoxins.<\/jats:p>","DOI":"10.3390\/pediatric15010009","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T05:37:31Z","timestamp":1675834651000},"page":"69-118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Patterns of Cannabis- and Substance-Related Congenital General Anomalies in Europe: A Geospatiotemporal and Causal Inferential Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3256-720X","authenticated-orcid":false,"given":"Albert Stuart","family":"Reece","sequence":"first","affiliation":[{"name":"Division of Psychiatry, University of Western Australia, Crawley, WA 6009, Australia"},{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary Kenneth","family":"Hulse","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University of Western Australia, Crawley, WA 6009, Australia"},{"name":"School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13892","DOI":"10.1038\/s41598-021-93411-5","article-title":"Epidemiological Overview of Multidimensional Chromosomal and Genome Toxicity of Cannabis Exposure in Congenital Anomalies and Cancer Development","volume":"11","author":"Reece","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_2","unstructured":"Reece, A.S., and Hulse, G.K. (2020, July 10). Available online: https:\/\/www.bing.com\/search?q=Cannabis+in+Pregnancy+%E2%80%93+Rejoinder%82C+Exposition+and+Cautionary+Tales&cvid=22538e20124c04711b92017489c92063214a&aqs=edge..92017469i92017457.92017439j92017480j92017481&pglt=92017443&FORM=ANSPA92017481&PC=U92017531."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1080\/15287390600748799","article-title":"Risk of Selected Birth Defects with Prenatal Illicit Drug Use, Hawaii, 1986\u20132002","volume":"70","author":"Forrester","year":"2006","journal-title":"J. Toxicol. Environ. Health Part A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1097\/ADM.0000000000000638","article-title":"Canadian Cannabis Consumption and Patterns of Congenital Anomalies: An Ecological Geospatial Analysis","volume":"14","author":"Reece","year":"2020","journal-title":"J. Addict. Med."},{"key":"ref_5","first-page":"1","article-title":"Cannabis Consumption Patterns Explain the East-West Gradient in Canadian Neural Tube Defect Incidence: An Ecological Study","volume":"6","author":"Reece","year":"2019","journal-title":"Glob. Pediatr. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1080\/15592294.2019.1633868","article-title":"Impacts of cannabinoid epigenetics on human development: Reflections on Murphy et. al. \u2018cannabinoid exposure and altered DNA methylation in rat and human sperm\u2019 epigenetics 2018; 13: 1208\u20131221","volume":"14","author":"Reece","year":"2019","journal-title":"Epigenetics"},{"key":"ref_7","first-page":"1","article-title":"Cannabinoid- and Substance-Relationships of European Congenital Anomaly Patterns: A Space-Time Panel Regression and Causal Inferential Study","volume":"8","author":"Reece","year":"2022","journal-title":"Environ. Epigenet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.35248\/2572-0775.19.4.154","article-title":"Effect of Cannabis Legalization on US Autism Incidence and Medium Term Projections","volume":"4","author":"Reece","year":"2019","journal-title":"Clin. Pediatr. Open Access"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.35248\/2572-0775.19.4.155","article-title":"Epidemiological Associations of Various Substances and Multiple Cannabinoids with Autism in USA","volume":"4","author":"Reece","year":"2019","journal-title":"Clin. Pediatr. Open Access"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1177\/0009922819861281","article-title":"Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends","volume":"58","author":"Reece","year":"2019","journal-title":"Clin. Pediatr."},{"key":"ref_11","unstructured":"Preedy, V., and Patel, V. (2022). Cannabis, Cannabinoids and Endocannabinoids, Elsevier. in press."},{"key":"ref_12","unstructured":"Preedy, V., and Patel, V. (2022). Cannabis, Cannabinoids and Endocannabinoids, Elsevier. in press."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s40360-020-00450-1","article-title":"Broad Spectrum epidemiological contribution of cannabis and other substances to the teratological profile of northern New South Wales: Geospatial and causal inference analysis","volume":"21","author":"Reece","year":"2020","journal-title":"BMC Pharmacol. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12887-021-02996-3","article-title":"Geotemporospatial and causal inference epidemiological analysis of US survey and overview of cannabis, cannabidiol and cannabinoid genotoxicity in relation to congenital anomalies 2001\u20132015","volume":"22","author":"Reece","year":"2022","journal-title":"BMC Pediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1186\/s12887-020-02431-z","article-title":"Contemporary epidemiology of rising atrial septal defect trends across USA 1991\u20132016: A combined ecological geospatiotemporal and causal inferential study","volume":"20","author":"Reece","year":"2020","journal-title":"BMC Pediatr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1186\/s12885-021-07924-3","article-title":"A geospatiotemporal and causal inference epidemiological exploration of substance and cannabinoid exposure as drivers of rising US pediatric cancer rates","volume":"21","author":"Reece","year":"2021","journal-title":"BMC Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1186\/s12885-021-08598-7","article-title":"Cannabinoid exposure as a major driver of pediatric acute lymphoid Leukaemia rates across the USA: Combined geospatial, multiple imputation and causal inference study","volume":"21","author":"Reece","year":"2021","journal-title":"BMC Cancer"},{"key":"ref_18","first-page":"n3114","article-title":"Rapid Response: Cannabinoid Genotoxic Trifecta\u2014Cancerogenesis, Clinical Teratogenesis and Cellular Ageing","volume":"376","author":"Reece","year":"2022","journal-title":"Br. Med. J."},{"key":"ref_19","first-page":"n3114","article-title":"Limblessness: Cannabinoids Inhibit Key Embryonic Morphogens both Directly and Epigenomically","volume":"376","author":"Reece","year":"2022","journal-title":"Br. Med. J."},{"key":"ref_20","first-page":"k3357","article-title":"Rapid Response: Known Cannabis Teratogenicity Needs to be Carefully Considered","volume":"362","author":"Reece","year":"2018","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100245","DOI":"10.1016\/j.lanepe.2021.100245","article-title":"Quadruple convergence\u2014Rising cannabis prevalence, intensity, concentration and use disorder treatment","volume":"10","author":"Reece","year":"2021","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100227","DOI":"10.1016\/j.lanepe.2021.100227","article-title":"Public health monitoring of cannabis use in Europe: Prevalence of use, cannabis potency, and treatment rates","volume":"10","author":"Manthey","year":"2021","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_23","unstructured":"United National Office of Drugs and Crime (2019). World Drug Report 2019, United National World Health Organization. Available online: https:\/\/wdr.unodc.org\/wdr2019\/index.html."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1139\/o92-162","article-title":"Cytoskeletal organization following cannabinoid treatment in undifferentiated and differentiated PC12 cells","volume":"70","author":"Tahir","year":"1992","journal-title":"Biochem. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0006-8993(98)00766-5","article-title":"Maternal exposure to delta9-tetrahydrocannabinol facilitates morphine self-administration behavior and changes regional binding to central mu opioid receptors in adult offspring female rats","volume":"807","author":"Vela","year":"1998","journal-title":"Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0304-3835(79)80088-9","article-title":"Mutagenic activity of marihuana smoke condensates","volume":"6","author":"Busch","year":"1979","journal-title":"Cancer Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.fct.2015.03.004","article-title":"Genotoxic properties of representatives of alkylindazoles and aminoalkyl-indoles which are consumed as synthetic cannabinoids","volume":"80","author":"Koller","year":"2015","journal-title":"Food Chem. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/0091-3057(91)90372-9","article-title":"Influence of marihuana on cellular structures and biochemical activities","volume":"40","author":"Tahir","year":"1991","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1159\/000137442","article-title":"Influence of cannabinoids on somatic cells in vivo","volume":"21","author":"Zimmerman","year":"1980","journal-title":"Pharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.taap.2014.03.014","article-title":"Investigation of the in vitro toxicological properties of the synthetic cannabimimetic drug CP-47,497-C8","volume":"277","author":"Koller","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.toxlet.2014.09.002","article-title":"Cannabinoid-induced changes in respiration of brain mitochondria","volume":"231","author":"Fisar","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1007\/s12031-015-0545-2","article-title":"Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria","volume":"56","author":"Singh","year":"2015","journal-title":"J. Mol. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s00204-018-2322-9","article-title":"Low doses of widely consumed cannabinoids (cannabidiol and cannabidivarin) cause DNA damage and chromosomal aberrations in human-derived cells","volume":"93","author":"Russo","year":"2018","journal-title":"Arch. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16057","DOI":"10.1038\/s41598-019-52336-w","article-title":"Cannabinoids Exacerbate Alcohol Teratogenesis by a CB1-Hedgehog Interaction","volume":"9","author":"Fish","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1007\/s00204-020-02821-3","article-title":"Following the adverse outcome pathway from micronucleus to cancer using H2B-eGFP transgenic healthy stem cells","volume":"94","author":"Pfannkuche","year":"2020","journal-title":"Arch. Toxicol."},{"key":"ref_36","unstructured":"(2020, June 12). VACTERL Association, Available online: https:\/\/www.gosh.nhs.uk\/conditions-and-treatments\/conditions-we-treat\/vacterl-association-0\/."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/eep\/dvab009","article-title":"Refraining from use diminishes cannabis-associated epigenetic changes in human sperm","volume":"7","author":"Schrott","year":"2021","journal-title":"Environ. Epigenet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/j.1360-0443.2005.01322.x","article-title":"Cannabis use and other illicit drug use: Testing the cannabis gateway hypothesis","volume":"101","author":"Fergusson","year":"2006","journal-title":"Addiction"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.drugalcdep.2015.02.015","article-title":"Tobacco smoking and cannabis use in a longitudinal birth cohort: Evidence of reciprocal causal relationships","volume":"150","author":"Badiani","year":"2015","journal-title":"Drug Alcohol. Depend."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1037\/adb0000094","article-title":"Gateway to curiosity: Medical marijuana ads and intention and use during middle school. Psychol","volume":"29","author":"Miles","year":"2015","journal-title":"Addict. Behav."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1007\/s00127-015-1070-x","article-title":"Psychosocial sequelae of cannabis use and implications for policy: Findings from the Christchurch Health and Development Study","volume":"50","author":"Fergusson","year":"2015","journal-title":"Soc. Psychiatry Psychiatr. Epidemiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/apa.12851","article-title":"The Gateway Hypothesis of substance abuse: Developmental, biological and societal perspectives","volume":"104","author":"Kandel","year":"2015","journal-title":"Acta. Paediatr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/ajad.12186","article-title":"A review of co-morbid tobacco and cannabis use disorders: Possible mechanisms to explain high rates of co-use","volume":"24","author":"Rabin","year":"2015","journal-title":"Am. J. Addict."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.drugpo.2014.07.011","article-title":"Probability and predictors of the cannabis gateway effect: A national study","volume":"26","author":"Jin","year":"2015","journal-title":"Int. J. Drug Policy"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.pmedr.2016.05.003","article-title":"\u201cGateway hypothesis\u201d and early drug use: Additional findings from tracking a population-based sample of adolescents to adulthood","volume":"4","author":"Minelli","year":"2016","journal-title":"Prev. Med. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6340","DOI":"10.2174\/1381612822666160813214023","article-title":"Cannabis Epidemiology: A Selective Review","volume":"22","author":"Anthony","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1093\/oxfordjournals.aje.a009666","article-title":"Attributable fraction for cardiac malformations","volume":"148","author":"Wilson","year":"1998","journal-title":"Am. J. Epidemiol."},{"key":"ref_48","first-page":"359","article-title":"Effects of Marijuana Inhalation on Spermatogenesis of the Rat","volume":"Volume 1","author":"Nahas","year":"1999","journal-title":"Marijuana in Medicine"},{"key":"ref_49","first-page":"347","article-title":"Effects of Cannabinoids on Spermatogensis in Mice","volume":"Volume 1","author":"Nahas","year":"1999","journal-title":"Marijuana in Medicine"},{"key":"ref_50","first-page":"25","article-title":"Effects of cannabis and natural cannabinoids on chromosomes and ova","volume":"44","author":"Morishima","year":"1984","journal-title":"NIDA Res. Monogr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0002-9378(16)33653-5","article-title":"Chromosome breakage in users of marihuana","volume":"118","author":"Stenchever","year":"1974","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/234227a0","article-title":"Morphological and cytochemical effects of marijuana cigarette smoke on epithelioid cells of lung explants from mice","volume":"234","author":"Leuchtenberger","year":"1971","journal-title":"Nature"},{"key":"ref_53","first-page":"371","article-title":"Hypoploid metaphases in cultured lymphocytes of marihuana smokers","volume":"22\u201323","author":"Morishima","year":"1978","journal-title":"Adv. Biosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/em.2860020206","article-title":"In vitro induction of segregational errors of chromosomes by natural cannabinoids in normal human lymphocytes","volume":"2","author":"Henrich","year":"1980","journal-title":"Environ. Mutagen."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/S0140-6736(09)61037-0","article-title":"Adverse health effects of non-medical cannabis use","volume":"374","author":"Hall","year":"2009","journal-title":"Lancet"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.mrfmmm.2016.05.002","article-title":"Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity","volume":"789","author":"Reece","year":"2016","journal-title":"Mutat. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1007\/s00204-015-1569-7","article-title":"Impact of a synthetic cannabinoid (CP-47,497-C8) on protein expression in human cells: Evidence for induction of inflammation and DNA damage","volume":"90","author":"Bileck","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.1007\/s00204-016-1664-4","article-title":"Genotoxic properties of XLR-11, a widely consumed synthetic cannabinoid, and of the benzoyl indole RCS-4","volume":"90","author":"Ferk","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s13402-013-0131-y","article-title":"Tumor protein D54 is a negative regulator of extracellular matrix-dependent migration and attachment in oral squamous cell carcinoma-derived cell lines","volume":"36","author":"Mukudai","year":"2013","journal-title":"Cell Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/etc.3575","article-title":"Increase in cannabis use may indirectly affect the health status of a freshwater species","volume":"36","author":"Parolini","year":"2017","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/BF01923013","article-title":"Mutagenicity testing of 3 hallucinogens: LSD, psilocybin and delta 9-THC, using the micronucleus test","volume":"34","year":"1978","journal-title":"Experientia"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature25432","article-title":"Chromosomal instability drives metastasis through a cytosolic DNA response","volume":"553","author":"Bakhoum","year":"2018","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S1043-6618(89)80051-9","article-title":"Genotoxicity of heroin and cannabinoids in humans","volume":"21","author":"Piatti","year":"1989","journal-title":"Pharmacol. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.scitotenv.2013.08.024","article-title":"Oxidative and genetic responses induced by Delta-9-tetrahydrocannabinol (Delta-9-THC) to Dreissena polymorpha","volume":"468\u2013469","author":"Parolini","year":"2014","journal-title":"Sci. Total Environ."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/BF00372766","article-title":"Delta-9-Tetrahydrocannabinol: Effect on macromolecular synthesis in human and other mammalian cells","volume":"35","author":"Blevins","year":"1976","journal-title":"Arch. Toxicol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0006-2952(81)90282-3","article-title":"Influence of psychoactive and nonpsychoactive cannabinoids on cell proliferation and macromolecular biosynthesis in human cells","volume":"30","author":"Mon","year":"1981","journal-title":"Biochem. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1016\/0006-2952(78)90553-1","article-title":"Influence of delta9-tetrahydrocannabinol on cell proliferation and macromolecular biosynthesis in human cells","volume":"27","author":"Mon","year":"1978","journal-title":"Biochem. Pharmacol."},{"key":"ref_68","first-page":"1748","article-title":"Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes","volume":"36","author":"Nahas","year":"1977","journal-title":"Fed. Proc."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1159\/000136610","article-title":"Action of delta 9-tetrahydrocannabinol on cell division and macromolecular synthesis in division-synchronized protozoa","volume":"14","author":"McClean","year":"1976","journal-title":"Pharmacology"},{"key":"ref_70","first-page":"241","article-title":"Protective and therapeutic effects of cannabis plant extract on liver cancer induced by dimethylnitrosamine in mice","volume":"50","author":"Hussein","year":"2014","journal-title":"Alex. J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/0006-2952(81)90282-3","article-title":"Influence of psychoactive and nonpsychoactive cannabinoids on chromatin structure and function in human cells","volume":"30","author":"Mon","year":"1981","journal-title":"Biochem. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"18707","DOI":"10.1074\/jbc.M113.545210","article-title":"Histone modifications are associated with Delta9-tetrahydrocannabinol-mediated alterations in antigen-specific T cell responses","volume":"289","author":"Yang","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1210\/jc.2004-1287","article-title":"Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function","volume":"90","author":"Rossato","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.biopsych.2011.06.027","article-title":"Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring","volume":"70","author":"DiNieri","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.biopsych.2021.09.017","article-title":"Prenatal \u0394(9)-Tetrahydrocannabinol Exposure in Males Leads to Motivational Disturbances Related to Striatal Epigenetic Dysregulation","volume":"92","author":"Ellis","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.biopsych.2015.09.014","article-title":"Epigenetic Effects of Cannabis Exposure","volume":"79","author":"Szutorisz","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/npp.2013.352","article-title":"Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation","volume":"39","author":"Szutorisz","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1038\/npp.2015.155","article-title":"Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated with Cross-Generational Effects of Adolescent THC Exposure","volume":"40","author":"Watson","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.neubiorev.2017.05.011","article-title":"High times for cannabis: Epigenetic imprint and its legacy on brain and behavior","volume":"85","author":"Szutorisz","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1080\/15592294.2018.1554521","article-title":"Cannabinoid exposure and altered DNA methylation in rat and human sperm","volume":"13","author":"Murphy","year":"2018","journal-title":"Epigenetics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/15592294.2019.1656158","article-title":"Cannabis use is associated with potentially heritable widespread changes in autism candidate gene DLGAP2 DNA methylation in sperm","volume":"15","author":"Schrott","year":"2019","journal-title":"Epigenetics"},{"key":"ref_82","first-page":"L1202","article-title":"Inhaled marijuana smoke disrupts mitochondrial energetics in pulmonary epithelial cells in vivo","volume":"290","author":"Sarafian","year":"2006","journal-title":"Am. J. Physiol."},{"key":"ref_83","first-page":"L298","article-title":"Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics","volume":"284","author":"Sarafian","year":"2003","journal-title":"Am. J. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"323706","DOI":"10.1155\/2015\/323706","article-title":"Tetrahydrocannabinol induces brain mitochondrial respiratory chain dysfunction and increases oxidative stress: A potential mechanism involved in cannabis-related stroke","volume":"2015","author":"Wolff","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(00)00170-9","article-title":"Changes in rat brain energetic metabolism after exposure to anandamide or Delta(9)-tetrahydrocannabinol","volume":"395","author":"Costa","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1016\/j.fertnstert.2008.03.075","article-title":"Cannabinoids inhibit the respiration of human sperm","volume":"91","author":"Badawy","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1056\/NEJMc1407928","article-title":"Adverse Health Effects of Marijuana Use","volume":"371","author":"Volkow","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"A19","DOI":"10.1016\/j.neurol.2014.01.081","article-title":"\u00c9tude de l\u2019effet du THC sur la respiration mitochondriale du cerveau de rat. Une piste de r\u00e9flexion pour expliquer le lien entre la consommation de cannabis et la survenue d\u2019infarctus c\u00e9r\u00e9bral chez l\u2019homme. Study of the effect of THC on mitochondrial respiration of the rat brain. One line of thought to explain the link between cannabis use and the occurrence of cerebral infarction in men Revue Neurologique, Neurological Review","volume":"170","author":"Wolff","year":"2014","journal-title":"Rev. Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s12035-011-8202-4","article-title":"Genes and pathways co-associated with the exposure to multiple drugs of abuse, including alcohol, amphetamine\/methamphetamine, cocaine, marijuana, morphine, and\/or nicotine: A review of proteomics analyses","volume":"44","author":"Wang","year":"2011","journal-title":"Mol. Neurobiol."},{"key":"ref_90","unstructured":"Eurocat Data (2020, June 12). Prevalence Charts and Tables. Available online: https:\/\/eu-rd-platform.jrc.ec.europa.eu\/eurocat\/eurocat-data\/prevalence_en."},{"key":"ref_91","unstructured":"(2020, June 12). Global Health Observatory. Available online: https:\/\/www.who.int\/data\/gho\/data\/indicators\/indicator-details\/GHO\/total-(recorded-unrecorded)-alcohol-per-capita-(15-)-consumption."},{"key":"ref_92","unstructured":"European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2020, June 12). Statistical Bulletin 2021\u2014Prevalence of Drug Use. Available online: https:\/\/www.emcdda.europa.eu\/data\/stats2021\/gps_en."},{"key":"ref_93","unstructured":"The World Bank: Crude Data (2020, June 12). Adjusted Net National Income per Capita (Current US$). Available online: https:\/\/data.worldbank.org\/indicator\/NY.ADJ.NNTY.PC.CD."},{"key":"ref_94","unstructured":"(2020, June 12). R: A Language and Environment for Statistical Computing. Available online: https:\/\/cran.r-project.org\/."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the Tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"439","DOI":"10.32614\/RJ-2018-009","article-title":"Simple Features for R: Standardized Support for Spatial Vector Data","volume":"10","author":"Pebesma","year":"2018","journal-title":"R J."},{"key":"ref_97","unstructured":"Viridis (2020, June 12). Default Color Maps from \u2018Matplotlib\u2019. Available online: https:\/\/CRAN.R-project.org\/package=viridis."},{"key":"ref_98","unstructured":"Colorplaner (2020, June 12). ggplot2 Extension to Visualize Two Variables per Color Aesthetic through Colorspace Projection. Available online: https:\/\/github.com\/wmurphyrd\/colorplaner."},{"key":"ref_99","unstructured":"Pinheiro, J., Bates, D., DebRoy, S., Sarkar, D., and R Core Team (2020). nlme: Linear and Nonlinear Mixed Effects Models. R Compr. R Arch. Netw., 1, Available online: https:\/\/CRAN.R-project.org\/package=nlme."},{"key":"ref_100","unstructured":"Broom.mixed (2020, June 12). Tidying Methods for Mixed Models. Available online: http:\/\/github.com\/bbolker\/broom.mixed."},{"key":"ref_101","unstructured":"Broom (2020, June 12). Convert Statistical Objects into Tidy Tibbles. Available online: https:\/\/CRAN.R-project.org\/package=broom."},{"key":"ref_102","unstructured":"Leeper, T.J. (2021). Margins: Marginal Effects for Model Objects, Massachusetts Institute of Technology. R Package Version."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v077.i01","article-title":"Ranger: A Fast Implementation of Random Forests for High Dimensional Data in C++ and R","volume":"77","author":"Wright","year":"2017","journal-title":"J. Stat. Softw."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"343","DOI":"10.32614\/RJ-2020-013","article-title":"Variable Importance Plots\u2014An Introduction to the vip Package","volume":"12","author":"Greenwell","year":"2021","journal-title":"R J."},{"key":"ref_105","unstructured":"(2020, January 12). Package \u2018Plm\u2019. Available online: https:\/\/cran.r-project.org\/web\/packages\/plm\/plm.pdf."},{"key":"ref_106","first-page":"1","article-title":"The spdep Package","volume":"1","author":"Bivand","year":"2007","journal-title":"Compr. R Arch. Netw."},{"key":"ref_107","first-page":"1","article-title":"splm: Spatial Panel Data Models in R","volume":"47","author":"Millo","year":"2012","journal-title":"J. Stast. Softw."},{"key":"ref_108","unstructured":"Millo, G., and Piras, G. (2018). Package \u2018Splm\u2019, CRAN (Central R-Archive Network). Available online: https:\/\/cran.r-project.org\/web\/packages\/splm\/splm.pdf."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Croissant, Y., and Millo, G. (2019). Panel Data Econometrics with R, John Wiley and Sons.","DOI":"10.1002\/9781119504641"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v043.i13","article-title":"ipw: An R Package for Inverse Probability Weighting","volume":"43","author":"Wal","year":"2011","journal-title":"J. Stat. Softw."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7326\/M16-2607","article-title":"Sensitivity Analysis in Observational Research: Introducing the E-Value","volume":"167","author":"VanderWeele","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1097\/EDE.0000000000001238","article-title":"E-values and incidence density sampling","volume":"31","author":"VanderWeele","year":"2020","journal-title":"Epidemiology"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1093\/ije\/dyaa094","article-title":"Commentary: Developing best-practice guidelines for the reporting of E-values","volume":"49","author":"VanderWeele","year":"2020","journal-title":"Int. J. Epidemiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/jci-2018-0007","article-title":"Technical Considerations in the Use of the E-Value","volume":"7","author":"VanderWeele","year":"2019","journal-title":"J. Causal Inference"},{"key":"ref_115","unstructured":"Pearl, J., and Mackaenzie, D. (2019). The Book of Why: The New Science of Cause and Effect, Basic Books. Available online: https:\/\/cran.r-project.org\/web\/packages\/EValue\/EValue.pdf."},{"key":"ref_116","first-page":"1","article-title":"Ethanol exposure induces neonatal neurodegeneration by enhancing CB1R Exon1 histone H4K8 acetylation and up-regulating CB1R function causing neurobehavioral abnormalities in adult mice","volume":"18","author":"Subbanna","year":"2014","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/jnc.13120","article-title":"Postnatal ethanol exposure alters levels of 2-arachidonylglycerol-metabolizing enzymes and pharmacological inhibition of monoacylglycerol lipase does not cause neurodegeneration in neonatal mice","volume":"134","author":"Subbanna","year":"2015","journal-title":"J. Neurochem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.alcohol.2017.01.014","article-title":"Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors","volume":"61","author":"Seleverstov","year":"2017","journal-title":"Alcohol Fayettev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3389\/fnmol.2018.00045","article-title":"CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice","volume":"11","author":"Subbanna","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/s41386-018-0181-y","article-title":"CB1R regulates CDK5 signaling and epigenetically controls Rac1 expression contributing to neurobehavioral abnormalities in mice postnatally exposed to ethanol","volume":"44","author":"Joshi","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1093\/ijnp\/pyaa017","article-title":"Postnatal Ethanol Exposure Activates HDAC-Mediated Histone Deacetylation, Impairs Synaptic Plasticity Gene Expression and Behavior in Mice","volume":"23","author":"Shivakumar","year":"2020","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Subbanna, S., and Basavarajappa, B.S. (2020). Postnatal Ethanol-Induced Neurodegeneration Involves CB1R-Mediated \u03b2-Catenin Degradation in Neonatal Mice. Brain Sci., 10.","DOI":"10.3390\/brainsci10050271"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Lussier, A.A., Bodnar, T.S., Moksa, M., Hirst, M., Kobor, M.S., and Weinberg, J. (2021). Prenatal Adversity Alters the Epigenetic Profile of the Prefrontal Cortex: Sexually Dimorphic Effects of Prenatal Alcohol Exposure and Food-Related Stress. Genes, 12.","DOI":"10.3390\/genes12111773"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"788630","DOI":"10.3389\/fnins.2021.788630","article-title":"Intersection of Epigenetic and Immune Alterations: Implications for Fetal Alcohol Spectrum Disorder and Mental Health","volume":"15","author":"Lussier","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/ajcn\/nqab081","article-title":"Polymorphisms in SLC44A1 are associated with cognitive improvement in children diagnosed with fetal alcohol spectrum disorder: An exploratory study of oral choline supplementation","volume":"114","author":"Smith","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.2174\/1570159X19666211101111430","article-title":"Transgenerational Abnormalities Induced by Paternal Preconceptual Alcohol Drinking. Findings from Humans and Animal Models","volume":"20","author":"Terracina","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e22035","DOI":"10.1096\/fj.202101131R","article-title":"Maternal background alters the penetrance of growth phenotypes and sex-specific placental adaptation of offspring sired by alcohol-exposed males","volume":"35","author":"Thomas","year":"2021","journal-title":"FASEB J."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Wall\u00e9n, E., Auvinen, P., and Kaminen-Ahola, N. (2021). The Effects of Early Prenatal Alcohol Exposure on Epigenome and Embryonic Development. Genes, 12.","DOI":"10.3390\/genes12071095"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"497","DOI":"10.4103\/1673-5374.314294","article-title":"Oligodendrocyte pathology in fetal alcohol spectrum disorders","volume":"17","author":"Darbinian","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"113919","DOI":"10.1016\/j.expneurol.2021.113919","article-title":"Potential roles of imprinted genes in the teratogenic effects of alcohol on the placenta, somatic growth, and the developing brain","volume":"347","author":"Gutherz","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMp2113319","article-title":"Methods of Public Health Research\u2014Strengthening Causal Inference from Observational Data","volume":"385","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_132","unstructured":"Reece, A.S., and Hulse, G.K. (2022). Epidemiological Overview of Cannabis- and Substance-Carcinogenesis in Europe: A Lagged Causal Inferential Panel Regression Modelling and Marginal Effects Study. Mendeley Data, manuscript submitted."},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Reece, A.S., and Hulse, G.K. (2023). Novel Insights into Potential Cannabis-Related Cancerogenesis from Recent Key Whole Epigenome Screen of Cannabis Dependence and Withdrawal: Epidemiological Comment and Explication of Schrott et al. Genes, 14.","DOI":"10.3390\/genes14010032"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1186\/s13690-022-00811-8","article-title":"Geotemporospatial and Causal Inferential Epidemiological Overview and Survey of USA Cannabis, Cannabidiol and Cannabinoid Genotoxicity Expressed in Cancer Incidence 2003\u20132017: Part 1\u2014Continuous Bivariate Analysis","volume":"80","author":"Reece","year":"2022","journal-title":"Arch. Public Health"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13690-022-00812-7","article-title":"Geotemporospatial and Causal Inferential Epidemiological Overview and Survey of USA Cannabis, Cannabidiol and Cannabinoid Genotoxicity Expressed in Cancer Incidence 2003\u20132017: Part 2\u2014Categorical Bivariate Analysis and Attributable Fractions","volume":"80","author":"Reece","year":"2022","journal-title":"Arch. Public Health"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13690-022-00813-6","article-title":"Geotemporospatial and Causal Inferential Epidemiological Overview and Survey of USA Cannabis, Cannabidiol and Cannabinoid Genotoxicity Expressed in Cancer Incidence 2003\u20132017: Part 3\u2014Spatiotemporal, Multivariable and Causal Inferential Pathfinding and Exploratory Analyses of Prostate and Ovarian Cancers","volume":"80","author":"Reece","year":"2022","journal-title":"Arch. Public Health"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e01160","DOI":"10.7554\/eLife.01160","article-title":"MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons","volume":"2","author":"Engelhard","year":"2013","journal-title":"eLife"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"763","DOI":"10.7326\/L17-0067","article-title":"Marijuana Use During Stages of Pregnancy in the United States","volume":"166","author":"Volkow","year":"2017","journal-title":"Ann. Intern. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1001\/jama.2016.18612","article-title":"The Risks of Marijuana Use During Pregnancy","volume":"317","author":"Volkow","year":"2017","journal-title":"JAMA"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1183\/09031936.00065707","article-title":"Cannabis use and risk of lung cancer: A case-control study","volume":"31","author":"Aldington","year":"2008","journal-title":"Eur. Respir J."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/01243894-200607000-00013","article-title":"Risk of lung cancer and past use of cannabis in Tunisia","volume":"1","author":"Voirin","year":"2006","journal-title":"J. Thorac. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1097\/JTO.0b013e31818ddcde","article-title":"Cannabis smoking and risk of lung cancer in men: A pooled analysis of three studies in Maghreb","volume":"3","author":"Berthiller","year":"2008","journal-title":"J. Thorac. Oncol."},{"key":"ref_143","first-page":"1071","article-title":"Marijuana use and increased risk of squamous cell carcinoma of the head and neck","volume":"8","author":"Zhang","year":"1999","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"103S","DOI":"10.1002\/j.1552-4604.2002.tb06010.x","article-title":"Marijuana smoking and head and neck cancer","volume":"42","author":"Hashibe","year":"2002","journal-title":"J. Clin. Pharmacol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1023\/A:1018427320658","article-title":"Marijuana use and cancer incidence (California, United States)","volume":"8","author":"Sidney","year":"1997","journal-title":"Cancer Causes Control."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/cncr.24159","article-title":"Association of marijuana use and the incidence of testicular germ cell tumors","volume":"115","author":"Daling","year":"2009","journal-title":"Cancer"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1023\/B:NEON.0000024746.87666.ed","article-title":"The risk for malignant primary adult-onset glioma in a large, multiethnic, managed-care cohort: Cigarette smoking and other lifestyle behaviors","volume":"68","author":"Efird","year":"2004","journal-title":"J. Neuro-Oncol."},{"key":"ref_148","first-page":"165","article-title":"Transitional cell carcinoma in a young heavy marihuana smoker","volume":"54","year":"2001","journal-title":"Arch. Esp. Urol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.urology.2005.07.005","article-title":"Association between marijuana use and transitional cell carcinoma","volume":"67","author":"Chacko","year":"2006","journal-title":"Urology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.urology.2005.08.006","article-title":"Transitional cell carcinoma associated with marijuana: Case report and review of the literature","volume":"67","author":"Nieder","year":"2006","journal-title":"Urology"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40360-021-00505-x","article-title":"Causal inference multiple imputation investigation of the impact of cannabinoids and other substances on ethnic differentials in US testicular cancer incidence","volume":"22","author":"Reece","year":"2021","journal-title":"BMC Pharmacol. Toxicol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"dvac006","DOI":"10.1093\/eep\/dvac006","article-title":"Geospatiotemporal and Causal Inference Study of Cannabis and Other Drugs as Risk Factors for Female Breast Cancer USA 2003\u20132017","volume":"8","author":"Reece","year":"2022","journal-title":"Environ. Epigenet."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Reece, A.S., and Hulse, G.K. (2022). Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph192416721"},{"key":"ref_154","unstructured":"Hulse, G.K., White, J., and Cape, G. (2002). Management of Alcohol and Drug Problems, Oxford University Press. [1st ed.]."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3596","DOI":"10.1210\/EN.2015-1315","article-title":"Lipid Abundance in Zebrafish Embryos Is Regulated by Complementary Actions of the Endocannabinoid System and Retinoic Acid Pathway","volume":"156","author":"Fraher","year":"2015","journal-title":"Endocrinology"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"219","DOI":"10.24869\/psyd.2019.219","article-title":"Genetic Susceptibility to Posttraumatic Stress Disorder: Analyses of the Oxytocin Receptor, Retinoic Acid Receptor-Related Orphan Receptor A and Cannabinoid Receptor 1 Genes","volume":"31","author":"Agani","year":"2019","journal-title":"Psychiatr. Danub."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1440-1746.2011.07007.x","article-title":"Retinoic acids and hepatic stellate cells in liver disease","volume":"27","author":"Lee","year":"2012","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/abbs\/gmx073","article-title":"Effects of cannabidiol interactions with Wnt\/beta-catenin pathway and PPARgamma on oxidative stress and neuroinflammation in Alzheimer\u2019s disease","volume":"49","author":"Vallee","year":"2017","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1089\/can.2018.0010","article-title":"Identification of Synergistic Interaction Between Cannabis-Derived Compounds for Cytotoxic Activity in Colorectal Cancer Cell Lines and Colon Polyps That Induces Apoptosis-Related Cell Death and Distinct Gene Expression","volume":"3","author":"Nallathambi","year":"2018","journal-title":"Cannabis. Cannabinoid. Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.brainresbull.2017.07.004","article-title":"Identifying novel members of the Wntless interactome through genetic and candidate gene approaches","volume":"138","author":"Petko","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"7503","DOI":"10.2147\/OTT.S181706","article-title":"miR-23b-3p and miR-130a-5p affect cell growth, migration and invasion by targeting CB1R via the Wnt\/beta-catenin signaling pathway in gastric carcinoma","volume":"11","author":"Xian","year":"2018","journal-title":"OncoTargets Ther."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.neuron.2019.06.003","article-title":"Non-canonical Wnt Signaling through Ryk Regulates the Generation of Somatostatin- and Parvalbumin-Expressing Cortical Interneurons","volume":"103","author":"McKenzie","year":"2019","journal-title":"Neuron"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.bmcl.2019.03.013","article-title":"Analyzing the role of cannabinoids as modulators of Wnt\/beta-catenin signaling pathway for their use in the management of neuropathic pain","volume":"29","author":"Nalli","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.plipres.2012.08.001","article-title":"Manipulating molecular switches in brown adipocytes and their precursors: A therapeutic potential","volume":"52","author":"Birerdinc","year":"2013","journal-title":"Prog. Lipid Res."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.2741\/3786","article-title":"Brown fat biology and thermogenesis","volume":"16","author":"Richard","year":"2011","journal-title":"Front. Biosci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1016\/j.cellsig.2013.07.025","article-title":"Orexin receptors: Multi-functional therapeutic targets for sleeping disorders, eating disorders, drug addiction, cancers and other physiological disorders","volume":"25","author":"Xu","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1016\/j.cellsig.2014.04.008","article-title":"Ubiquitination-dependent CARM1 degradation facilitates Notch1-mediated podocyte apoptosis in diabetic nephropathy","volume":"26","author":"Kim","year":"2014","journal-title":"Cell. Signal."},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Xapelli, S., Agasse, F., Sarda-Arroyo, L., Bernardino, L., Santos, T., Ribeiro, F.F., Valero, J., Braganca, J., Schitine, C., and de Melo Reis, R.A. (2013). Activation of type 1 cannabinoid receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063529"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"34709","DOI":"10.1074\/jbc.M112.350678","article-title":"The endocannabinoid, anandamide, augments Notch-1 signaling in cultured cortical neurons exposed to amyloid-beta and in the cortex of aged rats","volume":"287","author":"Tanveer","year":"2012","journal-title":"J. Biol. Chem"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.neuron.2013.02.036","article-title":"Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling","volume":"78","author":"Foldy","year":"2013","journal-title":"Neuron"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"23892","DOI":"10.1074\/jbc.M700678200","article-title":"The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor proliferation and neurogenesis","volume":"282","author":"Aguado","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1083\/jcb.200210164","article-title":"The FGF receptor uses the endocannabinoid signaling system to couple to an axonal growth response","volume":"160","author":"Williams","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_173","unstructured":"Willsher, K. (2020, June 10). Baby Arm Defects Prompt Nationwide Investigation in France. Available online: https:\/\/www.theguardian.com\/world\/2018\/oct\/31\/baby-arm-defects-prompt-nationwide-investigation-france."},{"key":"ref_174","unstructured":"Agence France-Presse in Paris (The Guardian, 2018). France to Investigate Cause of Upper Limb Defects in Babies, The Guardian."},{"key":"ref_175","unstructured":"Gant, J. (Daily Mail, 2019). Scientists are Baffled by Spatter of Babies Born without Hands or Arms in France, as Investigation Fails to Discover a Cause, Daily Mail."}],"container-title":["Pediatric Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2036-7503\/15\/1\/9\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:27:18Z","timestamp":1760120838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2036-7503\/15\/1\/9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,7]]},"references-count":175,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["pediatric15010009"],"URL":"https:\/\/doi.org\/10.3390\/pediatric15010009","relation":{},"ISSN":["2036-7503"],"issn-type":[{"value":"2036-7503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,7]]}}}