Prenatal Alcohol and Cannabinoid Exposure May Have Stronger Effects Together, Animal Studies Suggest

Animal research suggests that alcohol and cannabinoids may interact during early development, producing brain, facial and behavioral changes that are more pronounced when the substances are combined. The findings do not show that children exposed to cannabis and alcohol will develop risky behavior, but they add to concerns about using either substance during pregnancy—particularly together.

In a 2019 study published in Birth Defects Research, researchers at North Carolina Central University exposed zebrafish embryos to ethanol and cannabinoid compounds, including ACEA, a synthetic chemical that activates the CB1 cannabinoid receptor. They then examined the fish for developmental abnormalities and, later, tested juvenile fish in a “novel tank dive” assay used to study anxiety-like and risk-taking behavior.

At some doses, either compound alone produced little or no measurable behavioral change. In contrast, juvenile fish exposed to the combination showed more risk-taking behavior, swimming toward the top of the tank sooner than control fish. The researchers also observed developmental abnormalities when low cannabinoid exposure was paired with higher ethanol exposure.

The study examined a drug compound in zebrafish—not cannabis use in pregnant people and not children’s behavior. Zebrafish are useful for studying developmental biology because many of their genes and signaling pathways are shared with other vertebrates, but results in fish cannot be assumed to predict the effects of prenatal exposure in humans.

The same research group also reported that cannabinoid exposure could intensify alcohol-related developmental damage in mice and zebrafish. In the 2019 Scientific Reports study, cannabinoids including THC, CBD and synthetic compounds affected the Sonic Hedgehog signaling pathway, which helps regulate development of the brain, face and other tissues. Combined exposure to low doses of alcohol and certain cannabinoids produced more eye, facial and brain abnormalities than either exposure alone in the animal models.

Those findings provide a possible biological explanation for an interaction between alcohol and cannabinoids, but they do not establish the size of any risk in humans. The doses, timing and routes of exposure used in animal experiments may differ substantially from real-world use, and the studies cannot account for factors such as nutrition, tobacco exposure, other drugs, genetics or prenatal care.

A separate rat study published in Birth Defects Research in 2019 offers additional, but distinct, evidence. Researchers administered alcohol and the synthetic cannabinoid CP-55,940 to rat pups during postnatal days 4 through 9—a period considered comparable to the third trimester of human brain development. The animals exposed to both substances showed more severe overactivity than those exposed to either substance alone. Alcohol impaired spatial learning, while cannabinoid exposure affected some measures of anxiety-like behavior.

Because this experiment involved rat pups after birth, it should not be described as a direct study of prenatal exposure. It does, however, reinforce the broader question of whether alcohol and cannabinoid exposure can interact during sensitive periods of brain development.

Fetal alcohol spectrum disorders, or FASDs, are established consequences of prenatal alcohol exposure and can involve lifelong differences in learning, behavior, physical development and the nervous system. The animal studies found some FASD-like features, but they did not diagnose FASD in humans or prove that prenatal cannabis causes the disorder. More human research is needed, especially research that measures cannabis and alcohol exposure separately and together while accounting for other risk factors.

Health organizations nevertheless recommend avoiding both substances during pregnancy. The Centers for Disease Control and Prevention states that no known safe amount or safe time for alcohol use exists during pregnancy. The CDC also advises pregnant people not to use cannabis, noting that THC can reach the developing fetus and that prenatal cannabis exposure may be associated with later attention, memory, problem-solving and behavioral difficulties.

The American College of Obstetricians and Gynecologists recommends counseling patients to stop cannabis use during pregnancy. Anyone who is pregnant, planning a pregnancy or concerned about past exposure should discuss it confidentially with a healthcare professional. The most defensible conclusion from the current evidence is not that animal findings predict a specific outcome for an individual child, but that avoiding alcohol and cannabis during pregnancy is the safest course while researchers continue to clarify how these substances affect development.