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A novel synthetic, nonpsychoactive cannabinoid acid (HU‐320) with antiinflammatory properties in murine collagen‐induced arthritis
Abstract
Objective: To explore the antiarthritic potential of a novel synthetic cannabinoid acid, Hebrew University–320 (HU‐320), in the DBA/1 mouse model of arthritis, and to investigate in vitro antiinflammatory and immunosuppressive effects of HU‐320 on macrophages and lymphocytes. Methods: DBA/1 mice were immunized with bovine type II collagen (CII) to induce arthritis and then injected intraperitoneally daily with HU‐320. The effects of treatment on arthritic changes in hind feet were assessed clinically and histologically, and draining lymph node responses to CII were assayed. Murine splenic and human blood lymphocytes were cultured to study the effect of HU‐320 on polyclonal mitogenic stimulation. Macrophage cultures were set up to evaluate in vitro effects of HU‐320 on production of tumor necrosis factor α (TNFα) and reactive oxygen intermediates (ROIs). The effect of HU‐320 administration on lipopolysaccharide‐induced serum TNF levels was assayed using C57BL/6 mice. Bioactive TNF production was measured using BALB/c clone 7 target cells. Evaluation of HU‐320 psychoactivity was performed using established laboratory tests on Sabra mice. Results: Systemic daily administration of 1 and 2 mg/kg HU‐320 ameliorated established CII‐induced arthritis. Hind foot joints of treated mice were protected from pathologic damage. CII‐specific and polyclonal responses of murine and human lymphocytes were down‐modulated. HU‐320 inhibited production of TNF from mouse macrophages and of ROIs from RAW 264.7 cells and suppressed the rise in serum TNF level following endotoxin challenge. HU‐320 administration yielded no adverse psychotropic effects in mice. Conclusion: Our studies show that the novel synthetic cannabinoid acid HU‐320 has strong antiinflammatory and immunosuppressive properties while demonstrating no psychoactive effects. The profound suppressive effects on cellular immune responses and on the production of proinflammatory mediators all indicate its usefulness as a novel nonpsychoactive, synthetic antiinflammatory product.
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“Administration of CBD, or its synthetic analogs, attenuates clinical signs of arthritis and joint damage, while having an immunosuppressant effect in CIA (Haj et al, 2015;Malfait et al, 2000;Sumariwalla et al, 2004).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Sumariwalla et al, 2004
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“Administration of CBD, or its synthetic analogs, attenuates clinical signs of arthritis and joint damage, while having an immunosuppressant effect in CIA (Haj et al, 2015;Malfait et al, 2000;Sumariwalla et al, 2004).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Sumariwalla et al, 2004
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Metadata
- Authors
- Sumariwalla, P. F., Gallily, R., Tchilibon, S., Fride, E., Mechoulam, R., & Feldmann, M.
- Affiliations
- Imperial College London (GB)
- Hebrew University of Jerusalem (IL)
- Ariel University (IL)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2004-03
- Volume
- 50
- Issue
- 3
- Pages
- 985-998
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2056056547
- Cited by
- 134
- References
- 57
- Citations by year
- 2025: 5 · 2024: 4 · 2023: 5 · 2022: 5 · 2021: 11 · 2020: 4 · 2019: 8 · 2018: 7 · 2017: 4 · 2016: 6 · 2015: 10 · 2014: 7 · 2013: 2 · 2012: 3
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- collagen-induced arthritis, anti-inflammatory activity, immunosuppression, TNF-α, reactive oxygen species, macrophages, lymphocytes, cell-mediated immunity, DBA/1 mice
- MeSH terms
- Animals, Anti-Inflammatory Agents, Arthritis, Experimental, Cannabidiol, Cattle, Cells, Cultured, Central Nervous System, Cyclohexanecarboxylic Acids, Female, Humans, Immunity, Cellular, Immunosuppressive Agents, Joints, Lipopolysaccharides, Lymphocytes, Macrophages, Mice, Inbred BALB C, Mice, Inbred C57BL, Mitosis, Severity of Illness Index, Tumor Necrosis Factor-alpha, Mice
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