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

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, i.e., 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 on stress response via neuroinflammation and NLRP3 inflammasome modulation.