Title:The NLRP3 Inflammasome in Stress Response: Another Target for the
Promiscuous Cannabidiol
Volume: 21
Issue: 2
Author(s): Alice Hartmann, Carla Vila-Verde, Francisco S. Guimarães, Sâmia R. Joca and Sabrina F. Lisboa*
Affiliation:
- Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São
Paulo, Brazil
- BioMolecular Sciences Department, School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Brazil
Keywords:
Neuroinflammation, NLRP3 inflammasome, cannabidiol, stress, psychiatric disorders, animal models.
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, 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.