Evaluation of the involvement of neuronal and glial changes in the antipsychotic properties of cannabidiol

Abstract

Schizophrenia is a chronic, complex and heterogeneous psychiatric disorder. Despite intensive research, the causes of schizophrenia are still unknown. The main hypothesis to explain it is based on the imbalance of dopaminergic neurotransmission. Additionally, a glutamatergic hypothesis of schizophrenia has also been presented suggesting that a hypofunction of glutamatergic neurotransmission mediated by NMDA receptors may underlie specific aspects of schizophrenia. In addition to ideas about the neurochemical mechanisms, few studies have investigated the mechanisms of the possible relationship between schizophrenia and drug abuse of Cannabis sativa. ”9-tetrahydrocannabinol (”9-THC), the main psychotomimetic compound from Cannabis, induces psychotic reactions and cognitive changes similar to schizophrenia. However, cannabidiol (CBD), another important component from Cannabis, unlike ”9-THC, has no psychotomimetic properties. Preclinical and clinical studies have shown that CBD can induce similar effects to antipsychotic drugs. However, the antipsychotic properties of repeated treatment with CBD as well as its effects at the molecular level and the brain structures involved have not yet been investigated significantly. Indeed, recently, we observed that the repeated treatment with CBD attenuated the psychotomimetic effects induced by chronic administration of NMDA receptor antagonists (MK-801), a model that seems to better represent the behavioral, neurochemical and neuroanatomical changes observed in patients with schizophrenia. Thus, we would like to investigate the neuronal and glial changes associated to repeated treatment with MK-801 and the CBD effects on these changes. (AU)