CNR2 and scleroderma: Another synthetic cannabinoid, VCE-004.8, has also shown benefits in mouse models of scleroderma, reducing vascular collagen deposits, preventing macrophage infiltration, inhibiting the proliferation and migration of fibroblasts and decreasing overall dermal thickness through mechanisms mediated by CB2 and PPARγ; while CB2 seems to mediate the anti-inflammatory effects, such as reducing macrophage IL-1β secretion and reducing the inflammatory infiltrate, PPARγ seems to exhibit anti-fibrotic effects by inhibiting the TGF-β production through interaction with Smads signaling [78,142,143].