Cannabidiol reverses myeloperoxidase hyperactivity in the prefrontal cortex and striatum, and reduces protein carbonyls in the hippocampus in a ketamine-induced schizophrenia rat model.
Sofia de Almeida Queiroz, Linério Ribeiro de Novais Junior, Anita Beatriz Pacheco de Carvalho, Tiago Vicente da Silva, Suelen de Souza Ramos, Vicente Meneguzzo, Khiany Mathias, Anita Dal Bó Tiscoski, Natália Piacentini, Mariana Pereira de Souza Goldim, Betine Pinto Moehlecke Iser, Fabricia Petronilho, Antonio Inserra, Rafael Mariano de Bitencourt
Schizophrenia Research April 1, 2025 DOI: 10.1016/j.schres.2025.03.031 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Cannabidiol Risperidone |
| Duration | 10-day ketamine pre-treatment followed by 8-day CBD or risperidone treatment |
| Topics | CBD Ketamine Esketamine |
| Keywords | Rats Risperidone CBD Research Mental health treatment Schizophrenia therapy Antipsychotic medicine |
| Citations | 2 |
| Key points | Cannabidiol restored ketamine-induced behavioral deficits and reduced oxidative stress and neuroinflammation in brain regions relevant to schizophrenia without the anhedonia-like side effects observed with risperidone. |
Abstract
Schizophrenia (SCZ) has limited treatment options, often with significant side effects. Cannabidiol (CBD), a non-euphoric phytocannabinoid, has shown potential as a novel therapeutic option in SCZ due to antipsychotic-like, anti-inflammatory, and antioxidant properties. We compared the therapeutic effects of CBD and risperidone (RISP) in a rat model of SCZ induced by sub-chronic ketamine (KET), focusing on inflammatory and oxidative stress, and behavioral phenotypes. Rats were pre-treated with KET or saline (SAL) for 10 days followed by CBD or RISP for 8 days. Locomotion, anxiety- and anhedonia-like behavior, and recognition memory were assessed. Oxidative damage as measured by protein carbonyls, thiobarbituric acid reactive substances, and catalase activity, and the inflammation markers myeloperoxidase (MPO) activity and nitrite/nitrate (N/N) concentration ratio were assessed in the prefrontal cortex (PFC), hypothalamus (HYP), hippocampus (HPC), and striatum, brain areas relevant to SCZ. CBD restored the KET-induced decreased rearing behavior in the OFT, while RISP further decreased rearing. RISP treatment in control rats decreased rearing and elicited an anhedonic-like phenotype, while CBD did not. CBD, but not RISP restored the KET-induced increased levels of MPO activity in the PFC and the striatum, and protein carbonyls in the HPC. Post-KET treatment with RISP but not CBD decreased protein carbonyls in the PFC, and decreased the N/N concentration ratio in the HYP. CBD restored the KET-induced decrease in rearing behavior without inducing an anhedonic-like phenotype as observed with RISP. CBD, and to a lesser extent RISP restored the oxidative stress and neuroinflammation elicited by KET in the striatum, HPC, and PFC. These findings support the possibility that the antipsychotic effects of CBD might be mediated by its antioxidant and anti-inflammatory effects.
Comparable studies
Other preclinical and animal studies on CBD, most cited first.
Citations in the library
Cited by 3
- Investigating the effects of chlorogenic acid on novel object recognition memory impairment, hyperlocomotion, and prefrontal BDNF expression in a sub-chronic ketamine-induced schizophrenia-like rat model IBRO Neuroscience Reports July 24, 2026
- Which Came First? Utility of Preclinical Models in Cracking the Chicken-or-Egg Relationship between Cannabis Use and Schizophrenia Current Addiction Reports February 27, 2026
- A systematic review of ketamine's anxiolytic potential in rodent behavioral models of anxiety and PTSD. Pharmacology, Biochemistry, and Behavior February 2026
Cites 7
- Pharmacological characterization of cannabidiol as a negative allosteric modulator of the 5-HT2A receptor. Cellular signalling March 1, 2025
- Multi-level therapeutic actions of cannabidiol in ketamine-induced schizophrenia psychopathology in male rats. Neuropsychopharmacology December 1, 2024
- CBD Effects on Motor Profile and Neurobiological Indices Related to Glutamatergic Function Induced by Repeated Ketamine Pre-Administration Frontiers in Pharmacology October 27, 2021
- Sub-anesthetic and anesthetic ketamine produce different long-lasting behavioral phenotypes (24 h post-treatment) via inducing different brain-derived neurotrophic factor (BDNF) expression level in the hippocampus. Neurobiology of Learning and Memory December 5, 2019
- Effects of quetiapine and sertindole on subchronic ketamine-induced deficits in attentional set-shifting in rats. Psychopharmacology September 15, 2011
and 2 more in the library