Comprehensive Assessment of Cannabidiol and HU308 in Acute and Chronic Colitis Models: Efficacy, Safety, and Mechanistic Innovations

Cannabinoids are emerging as promising treatments for inflammatory diseases such as ulcerative colitis. Specifically, cannabinoid 2 (CB2) receptors, which are upregulated during inflammation, have been distinctively linked to anti-inflammatory and analgesic effects. HU308, a synthetic cannabinoid de...

Full description

Saved in:
Bibliographic Details
Published in:Cells (Basel, Switzerland) Vol. 13; no. 23; p. 2013
Main Authors: Thapa, Dinesh, Patil, Mohan, Warne, Leon N, Carlessi, Rodrigo, Falasca, Marco
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 01.12.2024
MDPI
Subjects:
Acute Disease
Ammonia
Analgesics
Animal models
Animals
Anti-inflammatory drugs
Cannabidiol
cannabidiol (CBD)
Cannabidiol - pharmacology
Cannabidiol - therapeutic use
cannabinoid 2 receptor
Cannabinoid CB2 receptors
Cannabinoids
Cannabinoids - pharmacology
Cannabinoids - therapeutic use
Chronic Disease
Chronic illnesses
Colitis - chemically induced
Colitis - drug therapy
Colitis, Ulcerative - chemically induced
Colitis, Ulcerative - drug therapy
Colon
Colon - drug effects
Colon - metabolism
Colon - pathology
Cytokines - metabolism
Design
Dextran
Dextran Sulfate
Disease Models, Animal
Drinking water
Drug dosages
Experiments
Female
Glucagon
Glucagon-like peptide 1
Glucagon-Like Peptide 1 - metabolism
Glucose
HU308
Inflammation
Inflammatory bowel disease
inflammatory bowel disease (IBD)
Inflammatory bowel diseases
Innovations
Laboratory animals
Male
Mice
Mice, Inbred C57BL
Pain
Receptor, Cannabinoid, CB2 - metabolism
Side effects
Sodium sulfate
Toxicity
Tumor necrosis factor-TNF
Ulcerative colitis
United States
Illinois
Missouri
St Louis Missouri
United States > US
HU308
cannabidiol (CBD)
cannabinoid 2 receptor
ulcerative colitis
inflammatory bowel disease (IBD)
inflammation
ISSN:2073-4409, 2073-4409
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cannabinoids are emerging as promising treatments for inflammatory diseases such as ulcerative colitis. Specifically, cannabinoid 2 (CB2) receptors, which are upregulated during inflammation, have been distinctively linked to anti-inflammatory and analgesic effects. HU308, a synthetic cannabinoid developed to activate CB2 receptors selectively, aims to minimize unwanted off-target side effects. This study evaluated the effectiveness of both cannabidiol (CBD) and HU308 in mouse models of dextran sodium sulphate (DSS)-induced colitis, which mimic the acute and chronic phases of ulcerative colitis. Mice were treated with DSS in drinking water (four percent for the acute model and one to two percent for the chronic model) to induce colitis, as indicated by increased disease activity index (DAI) scores and inflammatory markers. Treatment with 60 mg/kg of CBD, but not lower doses, significantly reduced colitis symptoms, such as inflammation, cytokine levels, and MPO activity, while also normalizing glucagon-like peptide-1 (GLP-1) levels. HU308 showed comparable efficacy to high-dose CBD (60 mg/kg) but at a much lower dose (2.5 mg/kg), without observable toxicity. HU308 effectively normalized DAI scores, colon inflammation, ammonia levels, and GLP-1 expression in both colitis models. These results suggest that both CBD and HU308 are promising treatments for ulcerative colitis. However, HU308 demonstrates enhanced therapeutic potential by achieving similar outcomes at a fraction of the dose required for CBD, reducing the risk of off-target side effects. The ability of HU308 to modulate GLP-1, a biomarker of gut endocrine function, further underscores its promise as a novel treatment option.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
These authors contributed equally to this work.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells13232013