RT journal article
T1 THC improves behavioural schizophrenia-like deficits that CBD fails to overcome: a comprehensive multilevel approach using the Poly I:C maternal immune activation.
A1 Lamanna-Rama, Nicolás
A1 Romero-Miguel, Diego
A1 Casquero-Veiga, Marta
A1 MacDowell, Karina S.
A1 Santa-Marta, C.
A1 Torres Sánchez, Sonia
A1 Berrocoso Domínguez, Esther María
A1 Leza, Juan Carlos
A1 Desco, Manuel
A1 Soto-Montenegro, María Luisa
A2 Neurociencias
A2 Psicología
K1 cannabidiol
K1 delta-9-tetrahidrocannabino
K1 endocannabinoid system
K1 inflammation
K1 magnetic resonance imaging
K1 oxidative stress
AB 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.
PB Elsevier
SN 0165-1781
YR 2024
FD 2024-01
LK http://hdl.handle.net/10498/34779
UL http://hdl.handle.net/10498/34779
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-may-2026