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Cited by 26Cannabis and Cannabinoid ResearchInflammatory mediators and NSAID effectsNatural Compounds in Disease Treatment

HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid

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Haj, Christeene G., Sumariwalla, Percy F., Hanuš, Lumír, Kogan, Natalya M., Yektin, Zhana, Mechoulam, Raphael, Feldmann, Mark, Gallily, Ruth·2015·The Journal of Pharmacology and Experimental Therapeutics
DOI 10.1124/jpet.115.226100PMC PMC4576666
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Abstract

Cannabidiol (CBD) is a component of cannabis, which does not cause the typical marijuana-type effects, but has a high potential for use in several therapeutic areas. In contrast to Δ(9)-tetrahydrocannabinol (Δ(9)-THC), it binds very weakly to the CB1 and CB2 cannabinoid receptors. It has potent activity in both in vitro and in vivo anti-inflammatory assays. Thus, it lowers the formation of tumor necrosis factor (TNF)-α, a proinflammatory cytokine, and was found to be an oral antiarthritic therapeutic in murine collagen-induced arthritis in vivo. However, in acidic media, it can cyclize to the psychoactive Δ(9)-THC. We report the synthesis of a novel CBD derivative, HU-444, which cannot be converted by acid cyclization into a Δ(9)-THC-like compound. In vitro HU-444 had anti-inflammatory activity (decrease of reactive oxygen intermediates and inhibition of TNF-α production by macrophages); in vivo it led to suppression of production of TNF-α and amelioration of liver damage as well as lowering of mouse collagen-induced arthritis. HU-444 did not cause Δ(9)-THC-like effects in mice. We believe that HU-444 represents a potential novel drug for rheumatoid arthritis and other inflammatory diseases.

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Cited by

Sorted by citations

Authors
Haj, C. G., Sumariwalla, P. F., Hanuš, L., Kogan, N. M., Yektin, Z., Mechoulam, R., Feldmann, M., & Gallily, R.
Affiliations
Hebrew University of Jerusalem (IL)
ORCID
Venue
The Journal of Pharmacology and Experimental Therapeutics
Publisher
Elsevier BV
Published
2015-10
Volume
355
Issue
1
Pages
66-75
ISSN
0022-3565 (ISSN-L)
DOI
10.1124/jpet.115.226100
PMC
PMC4576666
OpenAlex
W1943820892
Cited by
26
References
5
Citations by year
2026: 3 · 2025: 2 · 2023: 2 · 2022: 1 · 2020: 1 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 4
FWCI
2.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
Keywords
cannabidiol derivatives, delta-9-tetrahydrocannabinol, acid-catalyzed cyclization, TNF-α, collagen-induced arthritis, rheumatoid arthritis, reactive oxygen species, macrophages, liver injury, cannabinoid receptor binding
MeSH terms
Acetates, Animals, Anti-Inflammatory Agents, Arthritis, Experimental, Cannabidiol, Concanavalin A, Cyclohexanecarboxylic Acids, Female, Liver, Macrophages, Male, Nitric Oxide, Tumor Necrosis Factor-alpha, Reactive Oxygen Species, Cytoprotection, Receptors, Cannabinoid, Mice

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