2019
DOI: 10.1038/s41598-019-52336-w
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Cannabinoids Exacerbate Alcohol Teratogenesis by a CB1-Hedgehog Interaction

Abstract: We tested whether cannabinoids (CBs) potentiate alcohol-induced birth defects in mice and zebrafish, and explored the underlying pathogenic mechanisms on Sonic Hedgehog (Shh) signaling. The CBs, Δ9-THC, cannabidiol, HU-210, and CP 55,940 caused alcohol-like effects on craniofacial and brain development, phenocopying Shh mutations. Combined exposure to even low doses of alcohol with THC, HU-210, or CP 55,940 caused a greater incidence of birth defects, particularly of the eyes, than did either treatment alone. … Show more

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Cited by 83 publications
(102 citation statements)
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“…At this site, the difference in comorbid alcohol and marijuana use reported between mothers of FASD children and controls was not statistically significant, but substantial (6.5 vs. 1.4%). Given recent preclinical study findings (Fish et al, 2019), and the likelihood of underreporting, this is a concerning finding. Maternal alcohol use correlates significantly, but not strongly, with physical anomalies, poorer growth, and some neurobehavioral outcomes in this study and other studies (May et al, 2013b, 2016a, 2016b).…”
Section: Discussionmentioning
confidence: 88%
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“…At this site, the difference in comorbid alcohol and marijuana use reported between mothers of FASD children and controls was not statistically significant, but substantial (6.5 vs. 1.4%). Given recent preclinical study findings (Fish et al, 2019), and the likelihood of underreporting, this is a concerning finding. Maternal alcohol use correlates significantly, but not strongly, with physical anomalies, poorer growth, and some neurobehavioral outcomes in this study and other studies (May et al, 2013b, 2016a, 2016b).…”
Section: Discussionmentioning
confidence: 88%
“…Drinking 3 DDD or more prior to pregnancy is reported by many mothers of children with FASD, and this pattern may be continued by many individuals until relatively late pregnancy recognition and later visits to a healthcare provider than with other mothers. Prenatal alcohol exposure causes multiple problems for many of the children who are exposed at various levels and times during pregnancy, and it may also be exacerbated by comorbid exposure with other drugs (Brown et al, 2017; Fish et al, 2019; Hingson et al, 1982; Volkow et al, 2017). Children diagnosed with any of the diagnoses on the continuum of FASD manifested a variety of physical and neurobehavioral deficits not experienced by the typically developing children at age 7.…”
Section: Discussionmentioning
confidence: 99%
“…While alcohol is the most teratogenic of the drugs commonly used in the U.S., simultaneous other drug exposure is a public health concern due to synergistic drug effects which may increase harm to the developing fetus. Since tetrahydrocannabinol (THC) in marijuana has been demonstrated to be teratogenic, especially when used in combination with alcohol (Fish et al, 2019), comorbid alcohol and marijuana use reported by mothers of both the FASD and control maternal groups (6.3 vs. 1.6%) is troubling. Also, reports that many fathers had alcohol use problems raised questions of both social influence on mothers and an epigenetic effect on offspring.…”
Section: Discussionmentioning
confidence: 99%
“…Other drug use in pregnancy was highest among the mothers of children with ARND, and higher lifetime use was highest among mothers of children with FAS and PFAS. The former use may account for the poorer neurobehavioral performance of the ARND group (Fish et al, 2019).…”
Section: Discussionmentioning
confidence: 99%