The NLRP3 Inflammasome in Stress Response: Another Target for the Promiscuous Cannabidiol

Abstract

Many psychiatric patients do not respond to conventional therapy. There is a vast effort to investigate possible mechanisms involved in treatment resistance, trying to provide better treatment options, and several data points toward a possible involvement of inflammatory mechanisms. Microglia, glial and resident immune cells, are involved in complex responses in the brain, orchestrating homeostatic functions, such as synaptic pruning and maintaining neuronal activity. In contrast, microglia play a major role in neuroinflammation, neurodegeneration, and cell death. Increasing evidence implicate microglia dysfunction in neuropsychiatric disorders. The mechanisms are still unclear, but one pathway in microglia has received increased attention in the last 8 years: the NLRP3 inflammasome pathway. Stress response and inflammation, including microglia activation, can be attenuated by Cannabidiol (CBD). CBD has antidepressant, anti-stress, antipsychotic, anti-inflammatory, and other properties. CBD effects are mediated by direct or indirect modulation of many receptors, enzymes, and other targets. This review will highlight some findings for neuroinflammation and microglia involvement in stress-related psychiatric disorders, particularly addressing the NLRP3 inflammasome pathway. Moreover, we will discuss evidence and mechanisms for CBD effects in psychiatric disorders and animal models and address its potential effects in stress response via neuroinflammation and NLRP3 inflammasome modulation.

Cannabidiol Rescues TNF-α-Inhibited Proliferation, Migration, and Osteogenic/Odontogenic Differentiation of Dental Pulp Stem Cells

“…This is the first study to report the potential of CBD on rescuing the inflammation-induced catabolic effects in DPSCs' functions. Reports from the literature have shown the anti-inflammatory effect of CBD in neuron and intestinal tissues [54,55]. CBD inhibits LPS-induced inflammation in macrophages, lung epithelial cells, and fibroblasts [56].…”

Toll-like receptor 4 in the interface between neuroimmune response and behavioral alterations caused by stress

“…For instance, several pieces of evidence indicate that some, but not all, individuals suffering from psychiatric disorders have a proinflammatory profile. Some data indicate that this profile is related to symptom severity and could predict resistance to conventional antidepressant treatment [88,[194][195][196]. Moreover, several data show the antidepressant effects of anti-inflammatory drugs (for review, see [196]).…”

“…Some data indicate that this profile is related to symptom severity and could predict resistance to conventional antidepressant treatment [88,[194][195][196]. Moreover, several data show the antidepressant effects of anti-inflammatory drugs (for review, see [196]). Therefore, targeting immune system mechanisms could improve symptoms, allowing some patients to respond to treatment.…”

Informing the Cannabis Conjecture: From Life’s Beginnings to Mitochondria, Membranes and the Electrome—A Review

“…This might suggest that CBD could have a much more nuanced control of inflammation. Others have also suggested that CBD could be modulating the inflammasome, which could be key in how it might help in neuroinflammation and stress-related psychiatric conditions [191].…”

“…With regards to CBD, the fact that it maybe modulating the inflammasome [191] and, more broadly, displays some anti-inflammatory effects [193], as well as having anti-cancer activity, with a variety of mechanisms being suggested [125,126], does continue to indicate that its ability to modulate mitochondrial function is likely to be playing a key role in these effects. Furthermore, and as suggested, if cellular cooperativity and the bioelectricity are interlinked, this might also suggest that compounds like CBD are acting to restore the system to the dissipative Goldilocks zone.…”