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THC Can Contribute to Birth Defects in Mice, Study Finds

By Leo Bear-McGuinness

Published: Oct 07, 2021   
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Exposure to THC in the womb could increase the risk that genetically predisposed children are born with facial defects, according to a new rodent study published in the journal Development.

After injecting some unborn mice with THC, the scientists behind the study observed facial and cranial abnormalities in the mice that were genetically vulnerable to such defects.

Given that another group of genetically vulnerable mice, which weren’t injected with THC, developed normally without deficits, the researchers concluded that THC was the switch that activated the disfigurement-causing genes.

As mice are standard models for humans in scientific research, the authors of the study say that these observed effects of prenatal cannabis exposure could be mirrored in humans.

And as the number of people using cannabis while pregnant continues to increase in the US following legalization, the researchers say their study is further proof that cannabis consumption may be an inadvisable habit while pregnant.

THC in the womb

Serious birth defects affect approximately 8 million newborns each year and are a leading cause of infant deaths.

Many of these defects are due to problems in an embryo’s hedgehog signaling pathway, which coordinates the development of the skull, limbs, and other features as the embryo matures. It’s understood from previous research that endocannabinoids (cannabinoids naturally produced in the human body) can inhibit parts of the hedgehog signaling pathway and affect development.

So, to test how the phytocannabinoid (a cannabinoid from an external source) THC affects unborn mice, the researchers from the Icahn School of Medicine at Mount Sinai first sourced pregnant female mice, some of which had a genetic mutation that predisposed their offspring to develop facial defects. The females were then injected with a single dose of THC at 5, 10, or 15 milligram per kilogram (mg/kg) doses, the latter of which was roughly equivalent to a 34 mg dose in humans.

The females’ embryos were later isolated and assessed for malformations. The embryos that didn’t carry the mutant genes developed normally, whether they were exposed to THC or not. The embryos that didn’t receive THC, but were genetically vulnerable to deformities, also developed normally. But the vulnerable embryos that did receive THC developed facial and cranial defects, which were more pronounced if they had been given higher doses of THC.

As such, the researchers concluded that THC can inhibit an embryo’s hedgehog signaling pathway and affect fetal development.

“THC directly inhibits Hedgehog signalling in mice, but it is not a very powerful inhibitor; this is presumably why a genetic predisposition is required for it to cause holoprosencephaly [severe skull and facial defects] in mice,” Robert Krauss, a professor of developmental biology at the Icahn School of Medicine at Mount Sinai and lead author of the paper, said in a statement.

Krauss and his colleagues say that their findings highlight the need for more research into the effects of cannabis use during human pregnancy, and whether THC could be having similar effects on the human hedgehog signaling pathway.

“The THC concentration in cannabis is now very high, so it is important to perform epidemiology studies looking at whether cannabis consumption is associated with developmental defects,” Krauss said.

“Women are already advised not to consume cannabis while pregnant, but our results show that embryos are sensitive at a very early period, before many women know they are pregnant. Cannabis consumption may therefore be inadvisable even when women are trying to get pregnant,” he warned.

Cannabis and the unborn

Previous studies investigating the effects of cannabinoids on developing embryos have also found undesirable outcomes.

A study published in Birth Defects Research in 2019 found that, when exposed to cannabinoids and alcohol, zebrafish – which are another standard model for humans in scientific research – developed “riskier” behavior and displayed signs of fetal alcohol spectrum disorder (FASD).

“If cannabis is having the same effect as alcohol, then you would want to also recommend pregnant women avoid cannabis use during pregnancy,” Gregory Cole, a professor at North Carolina Central University and author of that study, told Analytical Cannabis at the time.

“They would have the same outcome for their baby, which could have a range of neurological and behavioral disorders that will continue into adulthood – they tend have more difficulties in school and can have trouble with the law because of the increased risk-taking behavior.”

But while zebrafish are widely accepted as good models for investigating neurodevelopmental disorders and gene-directed behavior, they still aren’t wholly comparable to humans. 

“So a major limitation would be that, yes, it’s in zebrafish,” said Cole. “And so you might argue that even if we’re looking at a gene that’s suggested to be involved in FASD in humans, our study might not extrapolate from zebrafish to humans.”

A study recently published in Human Reproduction found that cannabis use seemed to reduce the chances of a successful pregnancy in participants, particularly among women who had already lost a pregnancy.

“These findings highlight potential risks on fecundability among women attempting pregnancy with a history of pregnancy loss and the need for expanded evidence regarding the reproductive health effects of cannabis use in the current climate of increasing legalization,” Dr Sunni Mumford, an investigator at the National institutes of Health and lead researcher of that study, told Analytical Cannabis this February.

Another recent study found that, when exposed to THC, bovine eggs were significantly less likely to result in a viable pregnancy.


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