Fig. 3
From: Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis
Possible effects of fatty acid amid hydrolase (FAAH) inhibition on neuroinflammation. CB1 and TRPV1 are expressed throughout the brain by several cell types, including microglia. In addition, FAAH-degradable N-acylethanolamines activate several other anti-inflammatory pathways supporting the role of CB1. Since no data are available regarding the effects of FAAH on sympathetic activity or microglia, the following sequence is hypothetical in nature. Upon activation, microglia produce pro-inflammatory cytokines and CB1 activation opposes this (1). Since CB1 controls neurotransmitter release, hypothalamic norepinephrine is decreased by FAAH inhibition, restoring brain-immune system-joint communication (2). Damaged neuronal tissue generated by the pro-inflammatory milieu is regenerated by CB1 activation (3). FAAH inhibition elevates mood and depressive symptoms in patients disappear due to decreased brain cytokines levels (4). Rheumatoid arthritis patients often suffer from bad sleep quality, and this is surpassed by FAAH inhibition (5). In general, CB1 activation decreases neuronal excitability, and this supports the general anti-inflammatory effect on microglia, which are activated by glutamate (6). The STOP symbol indicates inhibition, the PRIORITY ROAD symbol indicates an enhancement of a given effect