Researchers have discovered that adolescent cannabis use might lead to the cerebral cortex’s thinning.
Their study, utilizing both MRI scans and mouse models, reveals that THC, the active substance in cannabis, induces shrinkage in neurons’ dendritic structures, critical for brain communication and function. As THC consumption rises among North American youth, this research underscores the urgency of understanding its impact on brain development and forming effective public health strategies.
Cannabis use may contribute to thinning of the cerebral cortex in adolescents, according to a recent study led by researchers Graciela Pineyro and Tomas Paus at CHU Sainte-Justine and the Université de Montréal Faculty of Medicine. The study, a collaborative project between two research teams with unique approaches, reveals that THC — tetrahydrocannabinol, the active component in cannabis — leads to the shrinking of dendritic arbors. These “antenna-like” structures in neurons are essential for neuron-to-neuron communication. As THC causes this shrinkage, certain areas of the cerebral cortex may undergo atrophy, a concerning effect at a stage of critical brain development.
“If we take the analogy of the brain as a computer, the neurons would be the central processor, receiving all information via the synapses through the dendritic network,” explains Tomas Paus, who is also a professor of psychiatry and neuroscience at Université de Montréal. “So a decrease in the data input to the central processor by dendrites makes it harder for the brain to learn new things, interact with people, cope with new situations, etc. In other words, it makes the brain more vulnerable to everything that can happen in a young person’s life.”
A multi-level approach to better understand the effect on humans
This project is notable for the complementary, multi-level nature of the methods used. “By analyzing magnetic resonance imaging (MRI) scans of the brains of a cohort of teenagers, we had already shown that young people who used cannabis before the age of 16 had a thinner cerebral cortex,” explains Tomas Paus. “However, this research method doesn’t allow us to draw any conclusions about causality, or to really understand THC’s effect on the brain cells.”
Given the limitations of MRI, the introduction of the mouse model by Graciela Pineyro’s team was key. “The model made it possible to demonstrate that THC modifies the expression of certain genes affecting the structure and function of synapses and dendrites,” explains Graciela Pineyro, who is also a professor in the Department of Pharmacology and Physiology at Université de Montréal. “The result is atrophy of the dendritic arborescence that could contribute to the thinning observed in certain regions of the cortex.”
Interestingly, these genes were also found in humans, particularly in the thinner cortical regions of the cohort adolescents who experimented with cannabis. By combining their distinct research methods, the two teams were thus able to determine with a high degree of certainty that the genes targeted by THC in the mouse model were also associated to the cortical thinning observed in adolescents.
With cannabis use on the rise among North American youth, and commercial cannabis products containing increasing concentrations of THC, it’s imperative that we improve our understanding of how this substance affects brain maturation and cognition. This successful collaborative study, involving cutting-edge techniques in cellular and molecular biology, imaging and bioinformatics analysis, is a step in the right direction for the development of effective public health measures.
Reference: “Cells and Molecules Underpinning Cannabis-Related Variations in Cortical Thickness during Adolescence” by 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, 8 October 2024, Journal of Neuroscience.
DOI: 10.1523/JNEUROSCI.2256-23.2024
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