Fig. 4
From: Cannabinoid-based drugs targeting CB1 and TRPV1, the sympathetic nervous system, and arthritis
Possible effects of CB1 antagonism and fatty acid amid hydrolase (FAAH) inhibition on spleen. The healthy spleen is sympathetically innervated and β-adrenergic signaling prevails. Arthritis leads to a loss of sympathetic fibers and β-adrenergic signaling is decreased in favor of pro-inflammatory α-adrenergic signaling (1). The different signaling zones are depicted by dotted lines. Hypothetically, CB1 antagonism leads to increased secretion of norepinephrine and its co-transmitters from sympathetic terminals. While the β-adrenergic zone would be increased (indicated by dotted arrows) (2), pro-inflammatory cytokine production (3) can be decreased with a concomitant rise in anti-inflammatory cytokines (4). Anti-inflammatory effects of β-adrenergic signaling are supported by direct effects of CB1 antagonists on immune cells and FAAH substrates engaging TRPV1 and possibly other anti-inflammatory receptors. The STOP symbol indicates inhibition, the PRIORITY ROAD symbol indicates an enhancement of a given effect. The involved mechanism (CB1 or FAAH) is given below the symbols