Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon

Objective: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronicall...

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Main Authors: Couch, Daniel G., Tasker, Chris, Theophilidou, Elena, Lund, Jonathan N., O'Sullivan, Saoirse
Format: Article
Published: Portland Press 2017
Online Access:https://eprints.nottingham.ac.uk/48096/
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author Couch, Daniel G.
Tasker, Chris
Theophilidou, Elena
Lund, Jonathan N.
O'Sullivan, Saoirse
author_facet Couch, Daniel G.
Tasker, Chris
Theophilidou, Elena
Lund, Jonathan N.
O'Sullivan, Saoirse
author_sort Couch, Daniel G.
building Nottingham Research Data Repository
collection Online Access
description Objective: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. Design: Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55. Results: IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2 antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti- inflammatory in IBD and appendicitis explants. Conclusion: PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy
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spelling nottingham-480962020-05-04T19:15:31Z https://eprints.nottingham.ac.uk/48096/ Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon Couch, Daniel G. Tasker, Chris Theophilidou, Elena Lund, Jonathan N. O'Sullivan, Saoirse Objective: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs, cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue. These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. Design: Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of interferon γ (IFNγ) and tumour necrosis factor α (TNFα; 10 ng/ml), inflammation and PEA (10 µM), inflammation and CBD (10 µM), and PEA or CBD alone, CBD or vehicle were added simultaneously with IFNγ. Nine intracellular signalling phosphoproteins were determined by multiplex. Inflammatory cytokine secretion was determined using ELISA. Receptor mechanisms were investigated using antagonists for CB1, CB2, PPARα, PPARγ, TRPV1 and GPR55. Results: IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants. Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants. CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2 antagonist AM630 and TRPV1 antagonist SB366791. PEA effects were blocked by the PPARα antagonist GW6471. PEA and CBD were anti- inflammatory in IBD and appendicitis explants. Conclusion: PEA and CBD are anti-inflammatory in the human colon. This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy Portland Press 2017-11-01 Article PeerReviewed Couch, Daniel G., Tasker, Chris, Theophilidou, Elena, Lund, Jonathan N. and O'Sullivan, Saoirse (2017) Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon. Clinical Science, 131 (21). pp. 2611-2626. ISSN 1470-8736 https://doi.org/10.1042/CS20171288 doi:10.1042/CS20171288 doi:10.1042/CS20171288
spellingShingle Couch, Daniel G.
Tasker, Chris
Theophilidou, Elena
Lund, Jonathan N.
O'Sullivan, Saoirse
Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
title Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
title_full Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
title_fullStr Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
title_full_unstemmed Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
title_short Cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
title_sort cannabidiol and palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon
url https://eprints.nottingham.ac.uk/48096/
https://eprints.nottingham.ac.uk/48096/
https://eprints.nottingham.ac.uk/48096/