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

Psychiatry Res. 2024 Jan:331:115643. doi: 10.1016/j.psychres.2023.115643. Epub 2023 Nov 27.


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.

MeSH terms

  • Adult
  • Anti-Inflammatory Agents
  • Cannabidiol* / pharmacology
  • Cannabidiol* / therapeutic use
  • Cannabinoids*
  • Cannabis*
  • Dronabinol / pharmacology
  • Female
  • Humans
  • Inflammation
  • Poly I-C
  • Pregnancy
  • Schizophrenia* / drug therapy
  • Schizophrenia* / metabolism


  • Cannabidiol
  • Dronabinol
  • Poly I-C
  • Cannabinoids
  • Anti-Inflammatory Agents