Published in the scientific journal Biomedicine & Pharmacotherapy, the study found that CBD treatment was able to normalize emotional behavior and reduce vulnerability to addiction in animals exposed to alcohol during early development. These effects were especially pronounced in female mice. The researchers also discovered that CBD helped correct gene alterations linked to the gut microbiota, pointing to a broader systemic impact beyond the brain.
Fetal alcohol spectrum disorder, often referred to as FASD, is the leading preventable cause of intellectual disability worldwide. It occurs when alcohol interferes with brain development at any point during pregnancy. People affected by FASD can experience lifelong challenges, including learning difficulties, emotional instability, higher rates of anxiety and depression, impaired impulse control, and an increased risk of addiction in adulthood.
Despite the scale of the problem, treatment options remain limited. “There is currently no approved pharmacological therapy that addresses the root causes of this disorder,” said Jorge Manzanares, professor at Miguel Hernández University and principal investigator of the study. “Only treatments that manage symptoms are available.”
Motivated by this gap, the research team explored whether CBD could help reverse the biological changes caused by alcohol exposure during development. The team included scientists from the Institute of Agrochemistry and Food Technology and the University of Turku.
Their work focused on the endocannabinoid system, a complex network of receptors and signaling molecules that helps regulate emotion, motivation, learning, and stress. Previous studies have shown that prenatal alcohol exposure disrupts this system, contributing to emotional disorders and heightened addiction risk later in life.
“CBD is a non addictive compound derived from cannabis that interacts with the endocannabinoid system,” Manzanares explained. “It also has well documented neuroprotective, anti inflammatory, and anxiety reducing properties.”
In the study, researchers first examined how alcohol exposure during the perinatal period affected behavior in mice. They identified specific brain and gut biomarkers linked to emotional dysregulation and addiction vulnerability. The animals were then given chronic CBD treatment starting at weaning, allowing researchers to observe whether early intervention could reverse these effects.
The results were striking. Mice exposed to alcohol during development showed anxiety like and depressive behaviors regardless of sex. Female mice also demonstrated a stronger motivation to consume alcohol. After CBD treatment, emotional behaviors returned to normal levels in both males and females. In females, CBD completely eliminated the increased drive to drink alcohol, bringing it in line with healthy control animals.
CBD also corrected alterations in key brain systems, including dopamine receptors and components of the endocannabinoid system that are closely linked to mood regulation and addiction. But the findings did not stop there.
A major contribution of the study was its focus on the gut brain connection. “The digestive system and the brain are in constant communication,” said Francisco Navarrete, first author of the study. “This interaction plays a critical role in both physical and mental health.”
The team found that early alcohol exposure disrupted the gut microbiota, creating an imbalance known as dysbiosis. CBD treatment was able to reverse this effect by restoring microbial diversity and increasing populations of bacteria associated with healthy gut brain communication. These changes differed between male and female mice, reflecting natural differences in their microbiota.
“Our data suggest that some of the sex differences seen in vulnerability to fetal alcohol spectrum disorder may originate in the gut rather than solely in the brain,” Navarrete said. The researchers also observed sex specific differences in genes related to the endocannabinoid system, further underscoring the complexity of the condition.
The researchers are careful to emphasize that these findings come from animal models and should not be interpreted as an endorsement of CBD use during pregnancy or as a way to counteract alcohol exposure. The only way to prevent fetal alcohol spectrum disorder is to avoid alcohol entirely during pregnancy.
Manzanares, who has studied the endocannabinoid system for more than three decades, leads the Translational Neuropsychopharmacology Laboratory at the Institute for Neurosciences, a research group that has spent over twenty years advancing understanding of addiction and brain disorders. In 2023, the team published the first study examining the effects of CBD on brain and behavioral changes in an animal model of fetal alcohol spectrum disorder.
Together, these findings suggest that CBD may hold promise as part of future therapeutic strategies for addressing the long term consequences of prenatal alcohol exposure, while also highlighting the critical role of the gut brain axis in neurodevelopmental disorders.
