Prolonged incubation with Δ9-tetrahydrocannabinol but not with cannabidiol induces synaptic alterations and mitochondrial impairment in immature and mature rat organotypic hippocampal slices.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie February 1, 2025 Costanza Mazzantini, Lorenzo Curti, Daniele Lana et al.
A seven-day exposure to THC reduced pre- and post-synaptic proteins (synaptophysin, vGlut1, PSD95) in both immature and mature hippocampal slices, while CBD increased PSD95 only in immature slices. THC also lowered membrane passive properties and intrinsic excitability and increased sEPSCs in immature CA1 pyramidal cells. Both cannabinoids impaired mitochondrial function by reducing mRNA expression of mitobiogenesis genes (VDAC1, UCP2, TFAM). THC, but not CBD, caused tissue disorganization and morphological changes in CA1 pyramidal neurons, astrocytes, and microglia in both slice types. These findings help explain the adolescent brain's vulnerability to psychotropic cannabinoids.