Kynurenines and the Endocannabinoid System in Schizophrenia

Schizophrenia has many aspects in which both kynurenines and the ECS are involved. Although both have already been separately reviewed in detail, their overlapping functions, mechanisms, and potential interaction in schizophrenia have yet to be elucidated. Therefore, the present review aimed to highlight such aspects. Accordingly, the most well-known overlapping areas include dopaminergic, glutamatergic, and GABAergic transmission regulation via cannabinoids and KYNA. Moreover, the most possible receptor mediator for KYNA in this mechanism is the astrocytic α7nAChR given that NMDAR inhibition by KYNA does not seem to influence glutamate release [61]. Inflammatory mechanisms contributing to the development of schizophrenia are complex and widespread and need to be studied more thoroughly. The overlapping structural, pharmacological, and anatomical properties between GPR35 and CBRs are also promising candidates for regulating the common aspects of inflammation associated with schizophrenia.

Though the treatment of schizophrenia still remains challenging, a better understanding of the possible connections between kynurenines and the ECS could introduce novel therapeutic compounds and targets for treatment. Such compounds could also compensate for limitations of currently available medications. While KAT II inhibitors and CBD are promising, it will be interesting to determine whether co-administration would yield a synergistic effect. Nonetheless, additional studies are needed to adequately explore the interaction between kynurenines and the ECS and to better understand their separate functioning.

Finally, parallel alterations in kynurenines/the KP and the ECS are present not only in schizophrenia but also in other neurological disorders, such as Alzheimer’s disease [38,335,336,337]. Thus, studying the interaction between kynurenines and associated elements and the ECS might also help us further understand mechanisms and disorders apart from schizophrenia.


I always believed the endocannabinoid system played a role in SZ.

I hope everyone reads this.

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