Children born with fetal alcohol spectrum disorder (FASD) endure a lifetime of emotional challenges, academic hurdles, and increased susceptibility to addiction. There is currently no medication that addresses the biological foundations of this condition. Researchers in Spain have now reported that cannabidiol (CBD), a non-psychoactive component of cannabis, has reversed critical consequences of prenatal alcohol exposure in mice, including behaviors akin to anxiety, vulnerability to addiction, and altered gut microbiota.
The study, published in Biomedicine & Pharmacotherapy, revealed that continuous CBD treatment beginning at weaning normalized emotional behaviors in both male and female mice exposed to alcohol during their development. In females, the treatment completely removed their increased urge to consume alcohol, restoring it to levels seen in healthy controls.
FASD represents the foremost preventable cause of intellectual disabilities globally. Alcohol exposure in utero interferes with brain development, leading to enduring impairments in emotional regulation and reward processing. Despite impacting millions, there are no sanctioned medications targeting the disorder’s fundamental biology; only treatments for symptoms exist.
**Restoring the Brain’s Reward Systems**
The research group at the Institute for Neurosciences concentrated on the endocannabinoid system, a signaling network crucial for regulating emotion, motivation, and responses to stress. Previous studies indicated that prenatal alcohol exposure disrupts this system’s balance.
CBD treatment rectified molecular alterations in the brain’s reward center, restoring dopamine receptors and components of the endocannabinoid system that had been compromised. These changes are not merely theoretical; they represent the mechanisms through which the brain processes pleasure, copes with stress, and manages emotional reactions.
“Despite its significant impact on society and health, there is currently no approved pharmacological treatment aimed at the core of the disorder,” states Jorge Manzanares.
Both male and female mice exhibited anxiety-like and depressive-like behaviors following prenatal alcohol exposure. CBD eliminated these behaviors in both sexes. However, the response in females was particularly noteworthy — their motivation to self-administer alcohol returned to normal levels, indicating that the treatment repaired the reward and stress response systems.
**The Gut’s Influence on Brain Damage**
Prenatal alcohol exposure harms not just the brain but also leads to long-lasting dysbiosis—an imbalance in gut bacteria that seems to exacerbate emotional distress via the gut-brain connection.
CBD reversed these gut changes. The treatment enhanced populations of beneficial bacteria such as Akkermansia and Bifidobacterium, recognized for their anti-inflammatory effects and support in maintaining a healthy gut lining. The microbial diversity that had been disrupted due to alcohol exposure was restored.
The effects on the gut varied between males and females, reflecting inherent sexual differences in microbiota composition. This implies that future treatments for FASD may require gender-specific strategies.
“Our findings indicate that some of the sexual differences in FASD vulnerability might stem from gut conditions rather than being limited to the brain,” explains Francisco Navarrete.
The researchers emphasize that this is a preclinical study. They do not propose that CBD can mitigate alcohol consumption during pregnancy or that it serves as a cure. Nonetheless, this research provides a guide for developing the first pharmacological solutions targeting the root causes of FASD, rather than merely addressing symptoms. For the time being, complete abstinence from alcohol during pregnancy is still the only proven preventative measure.
DOI: [https://doi.org/10.1016/j.biopha.2025.118791](https://doi.org/10.1016/j.biopha.2025.118791)