Interactions between the Kynurenine and the Endocannabinoid System with Special Emphasis on Migraine

Abstract

Both the kynurenine and the endocannabinoid systems are involved in several neurological disorders, such as migraine and there are increasing number of reports demonstrating that there are interactions of two systems. Although their cooperation has not yet been implicated in migraine, there are reports suggesting this possibility. Additionally, the individual role of the endocannabinoid and kynurenine system in migraine is reviewed here first, focusing on endocannabinoids, kynurenine metabolites, in particular kynurenic acid. Finally, the function of NMDA and cannabinoid receptors in the trigeminal system—which has a crucial role in the pathomechanisms of migraine—will also be discussed. The interaction of the endocannabinoid and kynurenine system has been demonstrated to be therapeutically relevant in a number of pathological conditions, such as cannabis addiction, psychosis, schizophrenia and epilepsy. Accordingly, the cross-talk of these two systems may imply potential mechanisms related to migraine, and may offer new approaches to manage the treatment of this neurological disorder.

Prenatal THC exposure raises kynurenic acid levels in the prefrontal cortex of adult rats

“…In spite of the fact that both THC and KYNA affect major neurotransmitters including glutamate, acetylcholine and dopamine, and can influence learning, memory and other cognitive functions in adult rodents (Zou and Kumar, 2018;Schwarcz et al, 2012), only very few studies have so far shown mutual interactions between the drug -and by extension endocannabinoids -and KYNA. In the adult brain, such interactions clearly exist, though many questions remain (Justinova et al, 2013;Colín-González et al, 2016;Nagy-Grócz et al, 2017;Secci et al, 2019). In the present study, prenatal treatment with THC did not influence the levels of either kynurenine or KYNA in maternal and fetal plasma or, importantly, in the fetal brain.…”

The Future of Migraine Prevention

“…3). [19][20][21][22][23][24] Unknown Knowns.-In this context, unknown knowns refers to aspects of preventive treatment that are known to be effective but are not widely used. The consequence of this lack of utilization is that the perceived need for new treatments is greater.…”

Tryptophan Metabolites Along the Microbiota-Gut-Brain Axis: An Interkingdom Communication System Influencing the Gut in Health and Disease

“…221,266 Several studies suggest that kynurenic acid and its synthetic analogues may offer novel therapeutic options for the treatment of neuropathic pain syndromes devoid of significant adverse effects. [289][290][291] Tryptophan metabolites and IBS-associated anxiety and depression. IBS patients may frequently experience high levels of anxiety and depression with respect to healthy subjects, regardless of the IBS subtype.…”