The antioxidant N-acetylcysteine prevents cortical neuropathological phenotypes caused by adolescent Δ-9-tetrahydrocannabinol exposure in male rats.

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.

Study at a glance

Abstract

Clinical and pre-clinical evidence demonstrates that adolescent Δ-9-tetrahydrocannabinol (THC) exposure, the primary psychoactive component of cannabis, increases the risk of developing neuropsychiatric symptoms in later life. The medial prefrontal cortex (mPFC) serves as a pathophysiological nexus point underlying many cannabis-related pathophysiological outcomes. Nevertheless, the molecular mechanisms underlying these risk factors are poorly understood. THC increases oxidative stress, which is a well-established causal factor for increased neuropsychiatric risk, including schizophrenia. N-acetylcysteine (NAC) is an antioxidant glutathione precursor that normalizes glutamate and GABA activity in neuropathological states. We examined if NAC may prevent the pathophysiological impacts of THC using a rodent model of adolescent brain development and chronic THC exposure. We report that NAC treatment prevents cognitive, synaptic, neuronal and neurochemical deficits induced by adolescent THC. These findings highlight the critical role of THC-induced oxidative stress as a contributing factor to cannabinoid-mediated neuropsychiatric risk and identifies a novel antioxidant treatment candidate for the prevention and/or reversal of these pathophysiological outcomes.