The antioxidant N-acetylcysteine prevents cortical neuropathological phenotypes caused by adolescent Δ-9-tetrahydrocannabinol exposure in male rats.
Hanna J Szkudlarek, Rajkamalpreet Singh Mann, Krystyna Wieczerzak, Mohammed Halit Sarikahya, Taygun C Uzuneser, Marta De Felice, Mar Rodríguez-ruiz, Juan Pablo Galindo, Mathusha Pusparajah, Shawn N Whitehead, Walter J Rushlow, Daniel B Hardy, Susanne Schmid, Ken K-C Yeung, Steven R Laviolette
Translational Psychiatry October 6, 2025 DOI: 10.1038/s41398-025-03580-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rodent model of adolescent brain development |
| Interventions | N-acetylcysteine Δ-9-tetrahydrocannabinol |
| Topics | Cannabis |
| Citations | 1 |
| Key findings | NAC treatment prevents cognitive, synaptic, neuronal, and neurochemical deficits induced by adolescent THC exposure in a rodent model. |
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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 16
- High-potency cannabis and the risk of psychosis The British Journal of Psychiatry November 30, 2009
- Δ-9-Tetrahydrocannabinol and Cannabidiol produce dissociable effects on prefrontal cortical executive function and regulation of affective behaviors Neuropsychopharmacology November 27, 2018
- Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption PLoS One November 4, 2013
- CBD enhances the cognitive score of adolescent rats prenatally exposed to THC and fine-tunes relevant effectors of hippocampal plasticity. Frontiers in Pharmacology July 31, 2023
- THC and CBD: Villain versus Hero? Insights into Adolescent Exposure. International Journal of Molecular Sciences March 9, 2023
and 11 more in the library