Experimental Cannabis Use Affects Cortical Thickness Among Adolescents

Experimentation with cannabis during adolescence may impact cortical thickness, according to study findings published in The Journal of Neuroscience.

Researchers conducted a 3-step study to identify the cellular and molecular underpinnings of the system-level relationships between cannabis experimentation during adolescence and variations in brain maturation.

Adolescent male mice were exposed to either delta-9-tetrahydrocannabinol (THC; 10 mg/kg) or synthetic cannabinoid WIN 55,212-2 (WIN; 3 mg/kg) injections, while control mice received sesame oil. Between-group differences in differentially expressed genes, spine numbers, and dendritic architecture in the frontal cortex were assessed.

Between 2003 and 2012, adolescent boys from the Saguenay-Lac-Saint-Jean region of Quebec, Canada were enrolled in the Saguenay Youth Study, a long-term prospective community-based cohort study. Participants who did vs did not experiment with cannabis prior to the age of 16 were assessed for between-group differences in cortical thickness in 34 brain regions of the left hemisphere measured via magnetic resonance imaging (MRI).

Group differences were spatially correlated with gene expression of human homologs of mouse-identified differentially expressed genes.

Six mice received THC, 4 mice received WIN, and 6 mice received sesame oil.

A total of 327 (mean age, 14.4) adolescent boys who did not experiment with cannabis before the age of 16 and 140 (mean age, 16.0; mean age at exposure, 13.8) adolescent boys who did so at least once in their life were included in the study.

In adolescent mice, THC preferentially targeted glial cells, while WIN affected pyramidal neurons. Both interventions modified nuclear-coded subunits in mitochondrial respiratory complexes and excitatory synapse genes.

The spatial expression of 13 THC-related human homologs of differentially expressed genes correlated with cannabis-related variations in cortical thickness. Co-expression patterns of these 13 genes with cell-specific markers of astrocytes, microglia, and a type of pyramidal cells enriched in dendrite-regulating genes were revealed by virtual histology.  

The spatial expression of 18 WIN-related human homologs of differentially expressed genes also correlated with group differences in cortical thickness and exhibited co-expression patterns with the same 3 cell types.

According to gene ontology analysis, a total of 37 THC-related human homologs were enriched in neuron projection development, while 33 WIN-related homologs were enriched in processes related to learning and memory.

Researchers deduced that cannabis experimentation during adolescence may influence cortical thickness via glutamatergic synapses and dendritic arborization.

Study limitations include the exclusion of girls and use of experimental models.

“Experimentation with cannabis during adolescence may influence cortical thickness by impacting glutamatergic synapses and dendritic arborization,” the study authors concluded.