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

Motwani, M; Bennett, F; Norris, P; Maini, A; George, MJ; Newson, J; Henderson, A; ... Gilroy, D; + view all (2018) Potent anti-inflammatory and pro-resolving effects of anabasum in a human model of self-resolving acute inflammation. Clinical Pharmacology and Therapeutics , 104 (4) pp. 675-686. 10.1002/cpt.980. Green open access

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Abstract

Anabasum is a synthetic analog of Δ8‐tetrahydrocannabinol (THC)‐11‐oic acid that in preclinical models of experimental inflammation exerts potent anti‐inflammatory actions with minimal central nervous system (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 (5 mg) 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 antiphagocytic prostanoids (PGE2, TxB2, and PGF2α) resulted in enhanced clearance of inflammatory stimulus from the injected site. Anabasum at the higher dose of 20 mg possessed the additional properties of triggering the biosynthesis of specialized pro‐resolving lipid mediators including LXA4, LXB4, RvD1, and RvD3. Collectively, we demonstrate for the first time a striking anti‐inflammatory and pro‐resolution effects of a synthetic analog of THC in healthy humans.

Type: Article
Title: Potent anti-inflammatory and pro-resolving effects of anabasum in a human model of self-resolving acute inflammation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cpt.980
Publisher version: https://doi.org/10.1002/cpt.980
Language: English
Additional information: Copyright © 2017, The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/10038971
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