A combined dose of marijuana and alcohol could make unborn children more likely to act recklessly in later life, according to a series of studies.

After dosing zebrafish embryos with either cannabis agonists, alcohol, or a combination of the two, the scientists behind one of the studies observed that the juvenile fish exposed to both substances displayed riskier behavior than the fish exposed to just one.

As zebrafish are widely accepted models for human biology, the scientists claim that these effects of prenatal exposure could be mirrored in humans.

Another study in the new round of research, all published in a special issue of the journal Birth Defects Research, detailed how cannabis and alcohol cause more disruption in brain development when combined than when taken separately in prenatal rat models.

As the number of women using cannabis while pregnant continues to increase in the US, the authors of the studies are calling on health care providers to treat prenatal cannabis use like prenatal alcohol use and warn mothers-to-be of these reported risks.





Taking a risk

“What we found was, with either cannabis or alcohol, at very low amounts they had no effect on behavior. But when these very low amounts were combined, it affected the zebrafish behavior,” said Gregory Cole, a professor at North Carolina Central University and author of the zebrafish study.

To test the effect of prenatal cannabis exposure on the perception of risk, Cole and his team first exposed the zebrafish embryos to either a cannabis agonist, ethanol, or a combination of the two substances. Once the embryos became juveniles, the team placed the fish in a tank and watched their behavior.

“When you put these zebrafish into a novel tank, they'll swim to the bottom and spend the first four or five minutes just swimming along the bottom of the tank,” he explained to Analytical Cannabis. “And so we look at [this behavior] as a predator avoidance activity – they can't be attacked below if they were in environment. And then, with time, they swim towards the top of the tank.”

“So if we treat fish with alcohol or cannabis and we put these fish in the model tank, within one minute they begin to swim towards the top of the tank. And so we interpreted it to mean its increased risk-taking behavior – they don't have that increased anxiety.”

Cole and his team saw this risky behavior as a symptom of fetal alcohol spectrum disorder (FASD), a condition caused by consuming alcohol while pregnant. It’s thought that up to 5 percent of US children could be living with FASD, which is typified by learning difficulties, changes in cranial structure, and risky behavior.

“[The dose of alcohol and cannabis] has an effect on altering behavior and even some cranial facial morphology of the fish which we see in humans with severe FASD – they have cranial-facial dysmorphology,” said Cole.

Considering that this risk of FASD seems to increase when alcohol is consumed alongside cannabis, Cole and his fellow authors are recommending that healthcare workers become more aware of this association and better advise their pregnant patients.

“If cannabis is having the same effect as alcohol, then you would want to also recommend pregnant women avoid cannabis use during pregnancy,” he continued. “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.”



Limitations and future research

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

“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.”

Because of marijuana’s status as a Schedule 1 drug under the US’s Controlled Substance Act, the plant and all its compounds are still regarded as having “no currently accepted medical use” by the federal government – a clause that has long hindered the progress of any cannabis study using human subjects.

However, this restriction may not necessarily stop Cole and his colleagues from conducting further, corroborating research.

“We have a collaborator at UNC Chapel Hill that is doing similar studies in mice right now and finding similar results,” he added. “So we think that we're going to see this in multiple animal models and hopefully in the future, they'll be able to start looking at humans as well.”