Cannabidiol attenuates behavioral changes in a rodent model of schizophrenia through 5-HT1A, but not CB1 and CB2 receptors
Although cannabidiol (CBD), a major constituent of the plant cannabis, is known to have antipsychotic effects, its effects on the negative and cognitive symptoms of schizophrenia are currently not well understood. Hence, a study was recently conducted on mice models of this disease to evaluate whether CBD could reduce the negative behavioral and cognitive deficits and additionally, identify the molecular target of these therapeutic actions.
By treating male mice with a chemical blocker of the NMDA brain receptor for 14 days, researchers created mice with deficits in the social interaction (SI) and novel object recognition (NOR) tests, which have been used to investigate the negative and cognitive symptoms of schizophrenia, respectively. These mice then received CBD injection for 7 days, after which they were re-assessed using the same tests. Data showed that CBD delivers similar therapeutic results as a drug currently used to treat schizophrenia.
In follow-up experiments, after blockage of NMDA, the researchers also used chemical compounds to inhibit the cannabinoid receptor type 1 (CB1), cannabinoid receptor type 2 (CB2), or the serotonin 1A receptor (5-HT1A) in different groups of mice. These three groups of mice then also received CBD injection and re-assessment. Data suggested that the therapeutic effects of CBD were lost in the mice treated with 5-HT1A inhibitor, but not in the other groups. This was intriguing, since the cannabinoid receptors have been known to interact with components of cannabis – hence their names – including CBD.
In summary, the study proved that CBD attenuates behavioral and cognitive impairments in the mice model of schizophrenia by activation of 5-HT1A receptor and therefore serve as a potential treatment of many severe symptoms of this mental illness.