Cells and Molecules Underpinning Cannabis-Related Variations in Cortical Thickness during Adolescence Xavier Navarri, Derek N. Robertson, Iness Charfi, Florian Wünnemann, Antônia Sâmia Fernandes do Nascimento, Giacomo Trottier, Sévérine Leclerc, Gregor U. Andelfinger, Graziella Di Cristo, Louis Richer, G. Bruce Pike, Zdenka Pausova, Graciela Piñeyro and Tomáš Paus
Cannabis use can lead to thinning of the cerebral cortex in adolescents, according to a recent study led by Graciela Pineyro and Tomas Paus, researchers at CHU Sainte-Justine and professors at the Faculty of Medicine of the Université de Montréal. Through a collaboration between two research labs with complementary approaches, the study demonstrates that tetrahydrocannabinol (THC), an active component of cannabis, causes dendritic arborization shrinkage, a "network of antennas" in neurons that is critical for communication between them. This results in atrophy in certain regions of the cerebral cortex, an unfortunate development at an age when the brain is still maturing.
"If we compare the brain to a computer, neurons would be the central processor, receiving all the information through the dendritic network via synapses," explains Tomas Paus, also a professor of psychiatry and neuroscience at UdeM. "Thus, a reduction in data input to the central processor impairs the brain's ability to learn new things, interact with others, handle new situations, and more. In other words, the shrinkage of the dendritic network makes the brain more vulnerable to whatever a young person might face in life."
This project stands out for its complementary and multi-level methodology. "Through MRI scans of adolescent brains, we previously showed that young people who used cannabis before age 16 had a thinner cerebral cortex," notes Tomas Paus. "However, this research method does not allow us to draw conclusions about causality or fully understand THC's effects on brain cells."
To address this limitation of MRI, the introduction of Graciela Pineyro's mouse model was a crucial addition. "This model allowed us to establish that THC alters the expression of certain genes that affect synapse and dendrite function and structure," says Pineyro, also a professor in UdeM's Department of Pharmacology and Physiology. "This results in atrophy of the dendritic structure, responsible for the thinning observed in specific cortical regions."
Interestingly, these genes identified in mice were also found in humans, particularly in the thinner cortical regions of adolescents in the study who had used cannabis. By combining their approaches, Graciela Pineyro and Tomas Paus deduced with high certainty that the genes targeted by THC in both young human and mouse brains are similarly affected.
As cannabis use rises among North American youth and commercial cannabis products contain increasing THC concentrations, it is essential to enhance our understanding of this substance's effects on brain maturation and cognition. The successful collaboration between the two research teams, who leveraged advanced techniques in cell and molecular biology, imaging, and bioinformatics analysis, marks a significant step toward developing effective public health measures.
The article "Cells and Molecules Underpinning Cannabis-Related Variations in Cortical Thickness during Adolescence," by Xavier Navarri and colleagues, including Graciela Pineyro and Tomas Paus, was published in the Journal of Neuroscience on October 9, 2024.
This content has been updated on 30 October 2024 at 22 h 24 min.
