{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T02:37:05Z","timestamp":1780367825321,"version":"3.54.1"},"reference-count":94,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Atrial septal defect (ASD) affects 1:11.3 children in some US states; however, the antecedents of these trends are yet to be identified. A total of 1882 ASD rates (ASDRs) for 2003\u20132020 were sourced from the National Birth Defects Prevention Network reports. A total of 406,893 ASDs are reported. Substance (cigarettes, binge alcohol, cannabis, cannabinoids, analgesics, cocaine) exposure data were taken from the National Survey of Drug Use and Health. Income and ethnicity data were derived from the US Census. Adjustment was performed by mixed effects, survey and generalized additive regression. Causal analysis was by inverse probability weighting and E-values. Data were analyzed in RStudio. The highest ASDR of 884\/10,000 live births was amongst Non-Hispanic Asians and Pacific Islanders in Nevada in 2016\u20132020. The 2005\u20132018 median ASDR rose &gt;12-fold in Nevada and New Mexico, &gt;6-fold in New York, and 4.2-fold nationally 1989\u20132020; it doubled in NY from 2012\u20132016 to 2016\u20132020. The average state ASDR rose supra-exponentially (p = 0.0075) and was associated with higher cannabis use states (p = Zero, Cohen\u2019s D = 1.24), apparently driven by cannabis legalization (p = Zero). Estimated exposures to \u03949THC, cannabidiol and cannabigerol were implicated (from p = 2.67 \u00d7 10\u201368). Cannabis-legal states were compared with others (mean ASDR (C.I.) 178.15 (131.68, 224.62) vs. 74.28 (70.60, 77.96), p = Zero; O.R. 1.82 (1.81, 1.84), E-values 3.04 (lower C.I. 3.02), Cohen\u2019s D 1.29 (0.96, 1.62)). Overall, 29\/39 (74.4%) E-value estimates were &gt;4; 39\/39 (100%) were &gt;1.25. Cannabis, cannabinoids and cannabis legalization are strong candidates for driving the US ASDR supra-exponentially. Estimates of many cannabinoids, including cannabidiol, \u03949THC, and cannabigerol, are implicated. The results are consistent with other large epidemiological studies. The importance of the results is magnified by the increasing legalization and penetration of cannabinoids into the US population. Since therapeutic abortion is not practiced for ASD, it may be used as a bellwether index of heritable transgenerational cannabinoid genotoxicity and epigenotoxicity associated with cannabinoid exposure.<\/jats:p>","DOI":"10.3390\/jox16020043","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:06:59Z","timestamp":1772467619000},"page":"43","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Cannabis and Cannabis Legalization on US Atrial Septal Defect Rates"],"prefix":"10.3390","volume":"16","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, 35 Stirling Hwy., Crawley, WA 6009, Australia"},{"name":"School of Medical and Health Sciences, Edith Cowan University, 27 Joondalup Dr., Joondalup, WA 6027, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7907-0233","authenticated-orcid":false,"given":"Gary Kenneth","family":"Hulse","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University of Western Australia, 35 Stirling Hwy., Crawley, WA 6009, Australia"},{"name":"School of Medical and Health Sciences, Edith Cowan University, 27 Joondalup Dr., Joondalup, WA 6027, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,1]]},"reference":[{"key":"ref_1","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. 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