Kynurenines and the Endocannabinoid System in Schizophrenia: Common Points and Potential Interactions

Abstract

Schizophrenia, which affects around 1% of the world’s population, has been described as a complex set of symptoms triggered by multiple factors. However, the exact background mechanisms remain to be explored, whereas therapeutic agents with excellent effectivity and safety profiles have yet to be developed. Kynurenines and the endocannabinoid system (ECS) play significant roles in both the development and manifestation of schizophrenia, which have been extensively studied and reviewed previously. Accordingly, kynurenines and the ECS share multiple features and mechanisms in schizophrenia, which have yet to be reviewed. Thus, the present study focuses on the main common points and potential interactions between kynurenines and the ECS in schizophrenia, which include (i) the regulation of glutamatergic/dopaminergic/γ-aminobutyric acidergic neurotransmission, (ii) their presence in astrocytes, and (iii) their role in inflammatory mechanisms. Additionally, promising pharmaceutical approaches involving the kynurenine pathway and the ECS will be reviewed herein.

Pro-Inflammatory Cytokines: Potential Links between the Endocannabinoid System and the Kynurenine Pathway in Depression

“…In fact, there is a growing body of evidence showing potential common points or clear evidence for the interaction of the ECS and the KP. These were discussed previously by our group [ 12 , 13 , 14 ] among others [ 15 , 16 , 17 , 18 ]. This review will further support the link between the ECS and KP in the aspect of depression by summarizing the data of pro-inflammatory cytokines, which can be regulated by exogenous cannabinoids and at the same time which can regulate the KP.…”

Alpha7 nicotinic‐N‐methyl‐D‐aspartate hypothesis in the treatment of schizophrenia and beyond

“…Substance use disorder (SUD) is prevalent in schizophrenia (Coyle, 2006; Koola et al, 2012, 2013). Nicotinic (Rahman, 2013; Salamone et al, 2014; Zádor et al, 2019) and NMDA (Salamone et al, 2014; Tomek, Lacrosse, Nemirovsky, & Olive, 2013; Zádor et al, 2019), receptors may be critically involved in the pathophysiology of addiction. Several medications in Table 2 may also be beneficial for SUD.…”

Is Cannabidiol During Neurodevelopment a Promising Therapy for Schizophrenia and Autism Spectrum Disorders?

“…Furthermore, they also share some pathophysiological mechanisms such as neuroinflammation ( Bjorklund et al, 2016 ; Cattane et al, 2018 ; Araujo et al, 2019 ), reduction in thalamus volume, amygdala and thalamus dysfunctions when processing social stimuli ( Barlati et al, 2020 ), as well as glutamatergic, GABAergic ( Cattane et al, 2018 ), and endocannabinoid (ECB) system dysfunctions ( Zamberletti et al, 2017 ; Zador et al, 2019 ; Borgan et al, 2020 ; Pietropaolo et al, 2020 ). The ECB system is widely expressed in the central nervous system, playing roles in synaptic plasticity regulation through retrograde signaling.…”

“…Neuroinflammation and oxidative stress are also implicated in neurodevelopmental alterations associated with this disorder ( Buckley, 2019 ; Lin and Lane, 2019 ). Impairments in neurotransmission functions are also described, such as the compromised dopaminergic system in the mesocortical, mesolimbic, and nigrostriatal pathways ( Guillin et al, 2007 ; McCutcheon et al, 2019 ), the glutamatergic hypofunction in the PFC ( Bondi et al, 2012 ; Snyder and Gao, 2020 ), and GABAergic, serotoninergic, and ECB system dysfunctions ( Eggers, 2013 ; Schmidt and Mirnics, 2015 ; Fakhoury, 2017 ; Cattane et al, 2018 ; Zador et al, 2019 ).…”