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

authors

  • Lamanna Rama, Nicolas
  • Romero Miguel, Diego
  • CASQUERO VEIGA, MARTA
  • MacDowell, Karina S.
  • Santa Marta, Cristina
  • Torres Sanchez, Sonia
  • Berrocoso, Esther
  • Leza, Juan C.
  • DESCO MENENDEZ, MANUEL
  • SOTO MONTENEGRO, Mª LUISA

publication date

  • January 2024

volume

  • 331

International Standard Serial Number (ISSN)

  • 0165-1781

Electronic International Standard Serial Number (EISSN)

  • 1872-7123

abstract

  • 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.

keywords

  • cannabidiol; delta-9-tetrahidrocannabinol; endocannabinoid system; inflammation; magnetic resonance imaging; oxidative stress