{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:29:33Z","timestamp":1789586973520,"version":"build-2803163510"},"reference-count":88,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"RAMBAM MED-TECH","award":["#250123"],"award-info":[{"award-number":["#250123"]}]},{"name":"Friends of Rambam","award":["#200525"],"award-info":[{"award-number":["#200525"]}]},{"name":"Raphael Pharmaceutical Inc.","award":["#060124"],"award-info":[{"award-number":["#060124"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints. Current treatments aim to relieve pain and limit joint damage; however, many are associated with significant side effects or high costs. Neutrophils play a critical role in RA development and progression by driving synovial inflammation and tissue damage, yet no approved therapies directly target neutrophil-mediated pathogenic mechanisms. Cannabinoids have demonstrated anti-inflammatory potential. Although cannabinoids have been studied in RA, the direct modulation of neutrophil-driven mechanisms by purified CBG has not been systematically addressed. To harness the cannabinoid potential, we investigated the effects of the purified cannabinoid Cannabigerol (CBG) on neutrophil-mediated immune responses in RA. Methods: We assessed the effects of CBG on human blood isolated neutrophil cytokine secretion, signal transduction and migration as ex vivo models. In addition, collagen antibody-induced arthritis (CAIA) was applied in C57BL\/6 wt mice, and immune-cell recruitment and cytokine secretion were examined after CBG treatment. Results: Ex vivo experiments demonstrated that CBG hampered the secretion of pro-inflammatory cytokines from human neutrophils in a dose-dependent manner (TNF-\u03b1 and IL-6 by 68% and 72%, respectively). Furthermore, CBG downregulated inflammatory signal transduction, such as P38-MAPK, ERK1\/2 and Akt phosphorylationpost neutrophil activation by 41%, 54% and 78%, respectively. Importantly, 60% of the CBG downregulation of IL-6 was consistent with the CB2 receptor axis in a selective way. In addition, CBG attenuated neutrophil migration toward IL-8 by 67%. To further evaluate CBG therapeutic capacity, we used CAIA as an in vivo model. CBG treatment resulted in improving mice arthritis clinical scores and body weight in comparison to RA-diseased mice. Moreover, CBG reduced leukocyte recruitment to the inflamed joints by 48%, primarily through the inhibition of neutrophil and monocyte cells to 27% and 49%, respectively. Additionally, CBG showed its anti-inflammatory effect by decreasing inflammatory cytokines like IL-6 and IL-1\u03b2 by 98% and 60% in the blood. Also, CBG reduced MCP-1 and IL-1\u03b2 cytokines in the joints by 22% and 38%, respectively. Conclusions: These results show that CBG has anti-inflammatory capacity and therapeutic potential in regulating neutrophil-mediated immunity in RA. These findings are preclinical and require further validation before therapeutic positioning.<\/jats:p>","DOI":"10.3390\/ph19040560","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T11:51:03Z","timestamp":1775130663000},"page":"560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cannabigerol (CBG) Modulates Neutrophil Activity and Ameliorates Rheumatoid Arthritis Pathogenesis"],"prefix":"10.3390","volume":"19","author":[{"given":"Miran","family":"Aswad","sequence":"first","affiliation":[{"name":"The Shanti Center for Medical Cannabis Research, Rambam Health Care Campus, Haifa 3109601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonina","family":"Pechkovsky","sequence":"additional","affiliation":[{"name":"The Shanti Center for Medical Cannabis Research, Rambam Health Care Campus, Haifa 3109601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haya","family":"Hamza","sequence":"additional","affiliation":[{"name":"The Shanti Center for Medical Cannabis Research, Rambam Health Care Campus, Haifa 3109601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6189-8609","authenticated-orcid":false,"given":"Igal","family":"Louria-Hayon","sequence":"additional","affiliation":[{"name":"The Shanti Center for Medical Cannabis Research, Rambam Health Care Campus, Haifa 3109601, Israel"},{"name":"Clinical Research Institute at Rambam (CRIR), Rambam Health Care Campus, Haifa 3109601, Israel"},{"name":"The Division of Research at Rambam, Rambam Health Care Campus, Haifa 3109601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid Arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat. 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