Endocannabinoids are similar to the cannabinoids present in cannabis, but they are found naturally in the body. Endocannabinoids—and cannabinoids—work through a signaling system that supports neurodevelopment, but whether manipulating this system prenatally has long-lasting effects remains unclear.
In a new JNeurosci study, researchers led by Ismael Galve-Roperh, from the Complutense University of Madrid, have used mice to explore this unknown.
The researchers decreased expression of an endocannabinoid receptor in the prefrontal cortex of prenatal mice and assessed the impact of this manipulation on gene expression, neural properties, and behavior after the mice were born. Cortical neurons of the offspring did not migrate to their proper locations in the brain.
Additionally, these mice had altered expression of genes related to cortex development, neuron structure, and neural signaling. On a behavioral level, the prenatal manipulation that lowered expression of this endocannabinoid receptor impaired social interaction and movement in offspring. These behavioral differences were reflective of the genetic and cellular changes that the researchers observed.
According to the researchers, this work suggests that hindering development by manipulating this system prenatally may lead to neuropsychiatric conditions, especially those involving social deficits. Because cannabis acts through the same receptor the authors manipulated in this study, this work has implications on the understanding of prenatal cannabis exposure.
More information:
Prenatal Downregulation of CB1 Cannabinoid Receptors in the Mouse Prefrontal Cortex Disrupts Cortical Lamination and Induces a Transcriptional Signature Associated with Social Interaction Deficits, JNeurosci (2025). DOI: 10.1523/JNEUROSCI.0120-25.2025
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