SEX-DIVERGENT EFFECTS OF ADOLESCENT CANNABIDIOL EXPOSURE ON ADULT SYNAPTIC PLASTICITY

Cannabis is the most widely consumed drug among adolescents, and prolonged cannabis exposure during this critical period of brain maturation may interfere with neuronal circuit development, leading persistent behavioural alterations. Previous studies in animal models showed that adolescent exposure to delta-9-tetrahydrocannabinol (THC), the principal psychotomimetic component in the plant, induces long-lasting behavioural and neurobiological changes. Cannabidiol (CBD), the major non-psychotomimetic component, has been suggested to attenuate THC-induced deficits. However, evidence indicates that CBD-rich/THC-poor combinations could also elicit adverse outcomes. Hence, despite the putative protective role of CBD, the impact of chronic CBD administration alone during adolescence on neuronal maturation and circuit refinement remains poorly understood.
In this study, we investigated the possible sex-dependent long-term effects of prolonged CBD exposure in adolescent rats on brain circuits development, focusing our attention on different glutamatergic and GABAergic synapse markers in the prefrontal cortex and hippocampus. Moreover, we evaluated whether adolescent CBD treatment could affect dendritic spine density and morphology in the same brain regions.
Preliminary data showed that, in rats prefrontal cortex region, adolescence CBD treatment does not induce lasting changes on the glutamatergic and GABAergic systems. While, in the hippocampus, adolescent CBD exposure seems to induce changes in the excitatory/inhibitory balance. Additionally, in females, prolonged CBD administration during adolescence seems to alter mainly dendritic spine maturation across brain regions.
These outcomes suggest that prolonged CBD exposure in adolescence could trigger lasting changes in the neuronal architecture of the adult brain mainly in female rats.