THC and CBD Can Reduce Neural Activity in Juvenile Zebrafish, Study Finds

Exposing an unborn child to THC and CBD could reduce their neural activity and locomotion, according to new study published in Scientific Reports. 

After incubating zebrafish embryos in THC and CBD solutions, the scientists behind the study observed that the juvenile fish were much less active than a normal counterpart would be. Indeed, the fish exposed to both THC and CBD were even less active than those which had just been exposed to one of the cannabis chemicals.

As zebrafish are accepted models for humans in scientific research (much like mice), the authors of the study say that these observed effects of prenatal cannabis exposure could be mirrored in humans.

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 consumers should think twice about their drug use while pregnant.

Swimming in CBD

To test the effects of the cannabinoids on the juvenile fish, the researchers placed a number of zebrafish embryos in solutions containing THC, CBD, or a combination of both. The embryos were then left to soak up the cannabinoids for ten hours – enough time for them to multiply their cells and enter into a new phase of development known as gastrulation.

Once removed from the cannabinoid solutions, the fish were free to develop as normal. And by day four, the scientists noticed that many of the fish displayed decreased neural activity.

By measuring the calcium in the fish’s brains – high calcium levels being an indicator of active neurons – the researchers found that neural activity decreased by 60-to-70 percent among the fish bathed in THC, and by more than 70 percent in the group immersed in CBD. This fall in neural activity was even more pronounced in the zebrafish exposed to both CBD and THC.

“The interesting part is when combined, like how it is found in a cannabis edible or cigarette, we needed much less to get the same reduction in neural activity,” Richard Kanyo, the lead author on the study and post-doctoral fellow at the University of Alberta, said in a statement.

By day five post-fertilization, the fish larvae were able to swim. As such, Kanyo and his team were able to observe the fish’s levels of locomotion, and they found them lacking. The larvae exposed to either THC or CBD displayed activity levels 20 percent lower than those of normally developed zebrafish, while those exposed to both cannabinoids were 80 percent less active.

“This reduction in locomotion is consistent with earlier studies as well,” Declan Ali, a professor of biology at the University of Alberta, said in a statement.

Although the concentrations of CBD and THC used in the experiment were higher than those found in the average joint, Ali and his colleagues have still urged cannabis consumers to think twice about their drug of choice if they’re thinking of having children.

“We’re not saying that these compounds are bad for you,” he said. “I think in some contexts – pain relief or reducing seizures – there’s a great potential there.

“However, what we’re seeing is cannabis is not all good for everyone all the time and probably should not be taken during pregnancy.”

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 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.”

Yet many recent studies that used models other than zebrafish have also highlighted concerns around prenatal cannabis use, fertility, and birth outcomes.

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.