THC improves behavioural schizophrenia-like deficits that CBD fails to overcome: a comprehensive multilevel approach using the Poly I:C maternal immune activation

• Published in: Psychiatry research 2024-01, Vol.331, p.115643-115643, Article 115643
• Main Authors: Lamanna-Rama, Nicolás, Romero-Miguel, Diego, Casquero-Veiga, Marta, MacDowell, Karina S., Santa-Marta, Cristina, Torres-Sánchez, Sonia, Berrocoso, Esther, Leza, Juan C, Desco, Manuel, Soto-Montenegro, María Luisa
• Format: Article
• Language: English
• Subjects: cannabidiol; delta-9-tetrahidrocannabinol; endocannabinoid system; inflammation; magnetic resonance imaging; oxidative stress
• ISSN: 0165-1781; 1872-7123
• DOI: 10.1016/j.psychres.2023.115643

•Prenatal infections and adolescent cannabis use are risk factors in schizophrenia•THC and CBD differentially modulate behaviour and brain structure•THC prevented PPI and some brain structural deficits in the MIA model•THC produced an inflammatory state in MIA-offspring, partially prevented by CBD•CBD did not prevent behavioural deficits but did prevent structural abnormalities Prenatal infections and cannabis use during adolescence are well-recognized risk factors for schizophrenia. As inflammation and oxidative stress (OS) contribute to this disorder, anti-inflammatory drugs have been proposed as potential therapies. This study aimed to evaluate the association between delta-9-tetrahydrocannabinol (THC) and schizophrenia-like abnormalities in a maternal immune activation (MIA) model. Additionally, we assessed the preventive effect of cannabidiol (CBD), a non-psychotropic/anti-inflammatory cannabinoid. THC and/or CBD were administered to Saline- and MIA-offspring during periadolescence. At adulthood, THC-exposed MIA-offspring showed significant improvements in sensorimotor gating deficits. Structural and metabolic brain changes were evaluated by magnetic resonance imaging, revealing cortical shrinkage in Saline- and enlargement in MIA-offspring after THC-exposure. Additionally, MIA-offspring displayed enlarged ventricles and decreased hippocampus, which were partially reverted by both cannabinoids. CBD prevented THC-induced reduction in the corpus callosum, despite affecting white matter structure. Post-mortem studies revealed detrimental effects of THC, including increased inflammation and oxidative stress. CBD partially reverted these pro-inflammatory alterations and modulated THC's effects on the endocannabinoid system. In conclusion, contrary to expectations, THC exhibited greater behavioural and morphometric benefits, despite promoting a pro-inflammatory state that CBD partially reverted. Further research is needed to elucidate the underlying mechanisms involved in the observed benefits of THC. [Display omitted]