Cannabinoid receptor type 2 as a promising new target for schizophrenia drugs

Contribution of CB2 receptors in schizophrenia-related symptoms in various animal models

​In Summary

Schizophrenia is a serious, chronic mental disorder that disrupts how a person thinks, feels and behaves. Its psychotic (also known as positive) symptoms include altered perceptions, abnormal thinking, and odd behaviors. Its negative symptoms are depression- and anxiety-like in nature. Among its cognitive symptoms are decreased attention, concentration, and memory.

The endocannabinoid system, which is mainly made up of signalling lipids called endocannabinoids and the cannabinoid receptors they bind to, are known to be expressed in brain cells and modulate psychological states. In particular, the cannabinoid receptor type 2 (CB2) appears to play important roles in the regulation of anxiety- and depression-related behaviours, cognition and locomotion, all of which are considered schizophrenia symptoms. These various effects of CB2 activity on schizophrenia symptoms are documented in a recent scientific report.

In brief, blockage of CB2 can reduce the concomitant depressive and anxious states. Indeed, drugs that block CB2 can control negative symptoms in schizophrenia as well as many other disorders with similar emotional states – although only when administered over a long period of time. In contrast, drugs that activate CB2 are proved to alleviate cognitive impairments. Such effects of CB2 activation are particularly important given that all current schizophrenia treatment strategies are ineffective in controlling cognitive symptoms. How can the conflicting impacts of CB2 on cognitive and negative symptoms in patients be moderated? Luckily, although its activation improves cognitive functions, inhibition of CB2 alone does not cause cognitive impairment, but does so only when certain other excitatory signal transmissions in the brain are simultaneously disrupted.


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