Potent anti-inflammatory and pro-resolving effects of anabasum in a human model of self-resolving acute inflammation.

Anabasum is a synthetic analogue of Δ⁸ – tetrahydrocannabinol (THC)-11-oic acid that in pre-clinical models of experimental inflammation exerts potent anti-inflammatory actions with minimal CNS cannabimimetic activity. Here we used a novel model of acute inflammation driven by i.d. UV-killed E. coli in healthy humans and found that Anabasum (5mg) exerted a potent anti-inflammatory effect equivalent to that of prednisolone in terms of inhibiting neutrophil infiltration, the hallmark of acute inflammation. These effects arose from the inhibition of the neutrophil chemoattractant LTB₄ , while the inhibition of anti-phagocytic prostanoids (PGE₂ , TxB₂ and PGF₂ α) resulted in enhanced clearance of inflammatory stimulus from the injected site. Anabasum at the higher dose of 20mg possessed the additional properties of triggering the biosynthesis of specialised pro-resolving lipid mediators including LXA₄ , LXB₄ , RvD1 and RvD3. Collectively, we demonstrate for the first-time striking anti-inflammatory and pro-resolution effects of a synthetic analogue of THC in healthy humans. This article is protected by copyright. All rights reserved.