{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:10:29Z","timestamp":1791259829751,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study investigates the immunomodulatory effects of a well-characterized cannabidiol (CBD)-rich cannabis extract, CAN296, on T lymphocytes (T cells), particularly Cluster of Differentiation 4 (CD4+) helper and Cluster of Differentiation 8 (CD8+) cytotoxic subsets, by examining T-cell activation, cytokine secretion, and cytotoxic molecule expression in comparison with the conventional treatments dexamethasone (DEX) and tacrolimus (TAC). It addresses key processes involved in the formation of premalignant immune-mediated lesions, such as those seen in oral lichen planus (OLP) and oral manifestations of graft-versus-host disease (oGVHD). CD4+ and CD8+ T cells were isolated from healthy donors and assessed in vitro for T cell activation via CD69 expression, secreted tumor necrosis factor alpha (TNF-\u03b1) and interferon gamma (IFN-\u03b3) levels according to enzyme-linked immunosorbent assay (ELISA), and cytotoxic molecule expression Granzyme B, Perforin, Fas Ligand (Fas-L) quantified by flow cytometry. Cells were treated with different doses of CAN296 (2, 4, 8 \u00b5g\/mL), DEX (0.4, 4, 40 \u00b5g\/mL), or TAC (0.1, 1, 10 ng\/mL), and all parameters were compared to untreated controls. CAN296 significantly inhibited T cell activation, reducing CD69 expression in CD4+ T cells to 2\u201311% and in CD8+ T cells to 5\u201317%. It also markedly suppressed TNF-\u03b1 secretion in CD4+ T cells at all concentrations (p &lt; 0.0001). In CD8+ T cells, CAN296 led to a near-complete reduction in TNF-\u03b1 and IFN-\u03b3, leaving both cytokines barely detectable at all tested doses (p &lt; 0.0001). The effect of cell inhibition was significantly more pronounced than that observed with DEX or TAC, displaying dose-dependent reductions. TAC inconsistently lowered TNF-\u03b1 while paradoxically increasing IFN-\u03b3 at lower concentrations. Additionally, CAN296 consistently suppressed cytotoxic molecule expression, reducing Granzyme B by 81\u201382%, Perforin by 40\u201353%, and Fas-L by 40\u201344%. DEX showed variable effects on cytotoxic molecule expression. At the same time, TAC demonstrated inconsistent modulation of Perforin and Granzyme B. Overall, CAN296 outperformed DEX and TAC, demonstrating more potent and consistent immunomodulatory effects. CBD-rich cannabis extract, CAN296, exhibits potent immunomodulatory properties by effectively inhibiting T cell activation, lowering pro-inflammatory cytokines, and suppressing cytotoxic molecule expression. Its efficacy surpasses conventional therapies like DEX and TAC, offering a promising novel treatment modality for T cell-mediated disorders, including OLP and oGVHD. These findings support further development of CAN296 formulations to optimize dosing and delivery, followed by clinical trials to validate its therapeutic potential.<\/jats:p>","DOI":"10.3390\/ijms262110711","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T16:18:42Z","timestamp":1762186722000},"page":"10711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunomodulatory Effects of a High-CBD Cannabis Extract: A Comparative Analysis with Conventional Therapies for Oral Lichen Planus and Graft-Versus-Host Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5319-0747","authenticated-orcid":false,"given":"Kifah","family":"Blal","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel"},{"name":"School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronen","family":"Rosenblum","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hila","family":"Novak-Kotzer","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiri","family":"Procaccia","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawad","family":"Abu Tair","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nardy","family":"Casap","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Meiri","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-5978","authenticated-orcid":false,"given":"Ofra","family":"Benny","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.archoralbio.2013.04.004","article-title":"Oral lichen planus: Focus on etiopathogenesis","volume":"58","author":"Payeras","year":"2013","journal-title":"Arch. 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