BRAIN ALTERATIONS INDUCED BY PROLONGED TREATMENT WITH CANNABINOIDS: AN <EM >IN VITRO</EM> STUDY

Cannabis is widely used in the population, with the highest prevalence among adolescents, leading to growing medical concerns regarding its chronic use and abuse. In this study, we analysed the functional and molecular mechanisms that might underlie brain alterations.
Rat organotypic hippocampal slice were exposed chronically for 7 days to 1 µM of Cannabidiol (CBD) or 1 µM of Δ⁹-tetrahydrocannabinol (THC) after 2 days (immature) or 10 days (mature) of culture in vitro. At the end of the treatment, slices were analysed by Western blotting, electrophysiology, RT-qPCR and electron microscopy to explore the molecular effects of chronic cannabinoid exposure.
THC reduced significantly the expression levels of pre- and postsynaptic proteins in both models, whereas CBD increased significantly PSD95 only in immature slices. Furthermore, THC increased the sEPSCs in CA1 pyramidal cells significantly only in immature slices. Chronic exposure to both cannabinoids reduced significantly the mitobiogenesis genes, in particular in mature slices. Moreover, both cannabinoids induced the precocious myelination process in the CA1 of immature slices. In mature slices, only THC induced myelin alterations and significantly increased MBP expression levels.
In conclusion our data show that chronic use of cannabinoids can lead to different effects depending on the stage of brain maturation.