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. Consistent with the hypothesis that these defects are caused by deficient Shh, we found that CBs reduced Shh signaling by inhibiting Smoothened (Smo), while Shh mRNA or a CB1 receptor antagonist attenuated CB-induced birth defects. Proximity ligation experiments identified novel CB1-Smo heteromers, suggesting allosteric CB1-Smo interactions. In addition to raising concerns about the safety of cannabinoid and alcohol exposure during early embryonic development, this study establishes a novel link between two distinct signaling pathways and has widespread implications for development, as well as diseases such as addiction and cancer.
Fetal Alcohol Spectrum Disorder (FASD) is common; recent conservative prevalence rates range from 1–5%1. Binge alcohol drinking (i.e. more than 4 or 5 drinks in two hours for women and men, respectively) is increasingly popular among young people, and is especially damaging to the embryo during the third to fourth weeks of pregnancy, when most pregnancies are unrecognized2,3. Alcohol exposure during this period causes characteristic craniofacial malformations of Fetal Alcohol Syndrome (FAS) including small palpebral fissures (micropthalmia), a smooth philtrum, and brain malformations in the holoprosencephaly spectrum3.
ffMarijuana use is also rising4, and about 4% of pregnancies are marijuana-exposed5, through either recreational use or as an anti-nausea self-medication. However, some subgroups of pregnancies have considerably more exposure6,7 and nearly 20% of a cohort of pregnant women in California, aged 18–24, report marijuana use8. As marijuana and other cannabinoids (CBs), such as cannabidiol (CBD), become increasingly legalized for medical or recreational purposes, and they remain perceived as low-risk substances9 safe to use during pregnancy, the incidence of CB-exposed pregnancies will rise even further. A recent study of births in Colorado found that the incidence of several birth defects has risen in the state during the period of marijuana legalization10.
Anne Russell thought it was safe to drink alcohol while pregnant with her son, Seth, but her actions led to him being born with Foetal Alcohol Spectrum Disorder (FASD) — a condition she believes pushed him into the criminal justice system.
Experts are calling for all children in Australia's criminal justice system to be assessed for FASD
It is believed up to 40 per cent of inmates in Australian prisons may have the disability, but most are undiagnosed
A federal inquiry into FASD support, prevention and diagnosis is due to release its findings next month
Ms Russell does not know what happened to her son in prison, but she says he has never been the same since.
Seth*, now 37, does not talk about the experience — in fact, he doesn't talk much at all. "He stays in his caravan 24/7," Ms Russell said. "He doesn't come out, he doesn't socialise. "That was basically the end of him being able to live a relatively normal life.
The fear that many more children have the condition but are undiagnosed has sparked calls for sweeping changes to Australia's criminal justice system.
Ms Russell said it was vital that children were assessed for FASD when they came into contact with youth justice and child protection systems.
"Early diagnosis, looking at target groups is so important," she said.
University of Queensland research fellow Natasha Reid said diagnosing patients with FASD could prevent them from reoffending.
Alcohol sales have spiked during the past month. It has long been acknowledged that Scotland has an ‘unhealthy relationship with alcohol’. Too much drinking carries with it heavy personal, economic, health and societal costs. The combination of being home-bound, feeling extraordinary stress or fear, as well as the cultural tendency to turn to both sex and alcohol for comfort and relief makes increasingly risky behaviour a near certainty.
One example of predictable ‘collateral damage’ from the current pandemic will be a significant rise in the cases of Fetal Alcohol Spectrum Disorders (FASD) across Scotland.
Alcohol exposure in utero is the world’s leading cause of neurodevelopmental (brain and nervous system) damage, learning disabilities and behavioural problems. FASD cannot be cured, reversed or outgrown, as it permanently compromises lives and life chances, e.g. by school failure, substance abuse, as well as being troubled and in trouble.
In fact, FASD is invisible in 90 per cent of the people affected and can be difficult to confirm, which means it is often misdiagnosed or simply overlooked – for instance, while the Scottish Government estimates that approximately 172,000 children, young and adults across Scotland are currently affected, there are between 500 and 1,000 undiagnosed FASD cases for every one officially confirmed.
There is no risk-free time during pregnancy, no safe type of alcohol or risk-free amount - which is why all four UK Chief Medical Officers advise that no alcohol should be consumed during pregnancy or if likely to conceive (including in the weeks/months before pregnancy is confirmed). Yet FASD is preventable in either of two ways: by not drinking during pregnancy - or by not getting pregnant while continuing to drink.
Is anything being said - or, better still, being done - to help prevent this specific ‘collateral damage’? Since most people are riveted on new information about what can be done to avoid harm during this pandemic, there is a great opportunity in this moment to prevent FASD.
Five Things You Should Know about Drinking Alcohol during Pregnancy
Drinking alcohol during pregnancy can cause miscarriage, stillbirth, and a range of lifelong physical, behavioral, and intellectual disabilities. These disabilities are known as fetal alcohol spectrum disorders, or FASDs. People with FASDs can have learning disabilities, hyperactivity, difficulty with attention, speech and language delays, low IQ, and poor reasoning and judgment skills. They can also have problems with their organs, including the heart and kidneys.
There is no known safe amount of alcohol use during pregnancy or while trying to get pregnant. All drinks with alcohol can affect a baby’s growth and development and cause FASDs. A 5-ounce glass of red or white wine has the same amount of alcohol as a 12-ounce can of beer or a 1.5-ounce shot of straight liquor.
There is no safe time to drink during pregnancy. Alcohol can cause problems for a developing baby throughout pregnancy, including before a woman knows she is pregnant. Most women will not know they are pregnant for up to 4 to 6 weeks.
Too many women continue to drink during pregnancy. About 1 in 9 pregnant women in the United States reports alcohol use in the past 30 days. And about 1 in 26 pregnant women in the United States reports binge drinking in the past 30 days (having four or more drinks at one time).
Fetal Alcohol Spectrum Disorders (FASDs) are completely preventable. FASDs are completely preventable if a woman does not drink alcohol during pregnancy. Why take the risk?
This study, in a representative sample of young people in detention in Western Australia, has
documented a high prevalence of FASD and severe neurodevelopmental impairment, the majority of which had not been previously identified. These findings highlight the vulnerability of young people, particularly Aboriginal youth, within the justice system and their significant need for improved diagnosis to identify their strengths and difficulties, and to guide and improve their rehabilitation.
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