Adolescent exposure to THC, the main psychoactive component of cannabis, increases the risk of later neuropsychiatric symptoms, and the medial prefrontal cortex is a key brain region involved. The antioxidant N-acetylcysteine (NAC) prevented cognitive, synaptic, neuronal, and neurochemical deficits caused by chronic adolescent THC exposure in a rodent model. This suggests that THC-induced oxidative stress contributes to neuropsychiatric risk and identifies NAC as a potential preventive treatment.
In rats, THC infused directly into the medial prefrontal cortex (PFC) caused strong panic-like responses, while CBD did not affect panic but blocked the formation of associative fear memories and impaired latent inhibition and oddity discrimination. CBD counteracted THC-induced panic and prevented THC-driven phosphorylation of ERK1/2. CBD's effects on perception and latent inhibition depended on 5-HT1A receptor transmission and were accompanied by reduced phosphorylation of p70S6K, independently of THC. The findings suggest dissociable molecular mechanisms: THC promotes panic via ERK1/2 phosphorylation, while CBD impairs perceptive functions via 5-HT1A receptors and reduced p70S6K phosphorylation.