{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:57:12Z","timestamp":1785427032838,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["634\/24"],"award-info":[{"award-number":["634\/24"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"award":["634\/24"],"award-info":[{"award-number":["634\/24"]}],"id":[{"id":"https:\/\/ror.org\/04sazxf24","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Neuroinflammation is a hallmark of multiple sclerosis (MS). MS is marked by glial cell activation, autoreactive T cells, and the release of pro-inflammatory cytokines and free radicals. Current therapeutic strategies aim to modulate the immune response using disease-modifying therapies, to slow disease progression. The specific aims of this study were: (a) to investigate the effect of cannabinoid acids on the release of glial neuroinflammatory mediators, (b) to examine the effect of intraperitoneally administered cannabinoid acids on symptoms of MS, and (c) to evaluate their effects on microglial and astrocyte activation and CD4+ T cell infiltration into the spinal cords of MS mice. Exposure of BV2 microglia to cannabinoid acids attenuated lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase by 40\u201390% it also reduced the release of nitric oxide and interleukin-17A. Among the cannabinoid acids tested, cannabidiolic acid (CBDA) significantly increased tumor necrosis factor alpha (TNF\u03b1) secretion by up to 40% in LPS-stimulated BV2 cells. Intraperitoneal administration of CBDA also resulted in a twofold increase in TNF\u03b1 secretion in splenocytes isolated from MS mice, compared to untreated MS controls. This study provides evidence that CBDA significantly reduces neurological scores, while both cannabinoid acids attenuate microgliosis, astrogliosis, and CD4+ T cell migration in lumbar spinal cord sections of MS mice. These compounds cross the blood\u2013brain barrier (BBB) and act directly within the central nervous system. The consistent elevation of TNF\u03b1 in the presence of CBDA across three experimental models suggests a distinctive immunomodulatory role for CBDA, with potential therapeutic implications in MS.<\/jats:p>","DOI":"10.3390\/molecules31071227","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T07:25:12Z","timestamp":1775633112000},"page":"1227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Neuroinflammatory Cannabinoid Acids as a New Therapeutic Approach for Multiple Sclerosis"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2899-1472","authenticated-orcid":false,"given":"Nitsan","family":"Sharon","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva P.O. Box 653, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Ventura","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva P.O. Box 653, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirit","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Institute of Soil Water and Environmental Sciences, Volcani Center, Rishon LeZion 15159, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Gorelick","sequence":"additional","affiliation":[{"name":"Eastern Regional Research and Development Center, Judea Center, Kiryat Arba 90100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7551-5488","authenticated-orcid":false,"given":"Shimon","family":"Ben-Shabat","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva P.O. 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Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.bbadis.2010.07.007","article-title":"Inflammation, demyelination, and degeneration\u2014Recent insights from MS pathology","volume":"1812","author":"Stadelmann","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nrneurol.2014.37","article-title":"Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis","volume":"10","author":"Friese","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Dom\u00ednguez, M. (2025). Neuroinflammation: Mechanisms, Dual Roles, and Therapeutic Strategies in Neurological Disorders. Curr. Issues Mol. Biol., 47.","DOI":"10.3390\/cimb47060417"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1093\/brain\/awp070","article-title":"The relation between inflammation and neurodegeneration in multiple sclerosis brains","volume":"132","author":"Frischer","year":"2009","journal-title":"Brain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1056\/NEJMra052130","article-title":"Multiple sclerosis\u2014The plaque and its pathogenesis","volume":"354","author":"Frohman","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103995","DOI":"10.1016\/j.msard.2022.103995","article-title":"Use of natalizumab in persons with multiple sclerosis: 2022 update","volume":"65","author":"Morrow","year":"2022","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"105435","DOI":"10.1016\/j.msard.2024.105435","article-title":"Consensus recommendations for diagnosis and treatment of Multiple Sclerosis: 2023 revision of the MENACTRIMS guidelines","volume":"83","author":"Yamout","year":"2024","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/s41392-025-02415-4","article-title":"Multiple sclerosis: Molecular pathogenesis and therapeutic intervention","volume":"10","author":"Eixarch","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1172\/JCI58649","article-title":"Multiple sclerosis","volume":"122","author":"Nylander","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1515\/revneuro-2018-0002","article-title":"Multiple sclerosis pathogenesis: Missing pieces of an old puzzle","volume":"30","author":"Rahmanzadeh","year":"2018","journal-title":"Rev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s40035-020-00221-2","article-title":"Neuroinflammation in neurodegenerative disorders: The roles of microglia and astrocytes","volume":"9","author":"Kwon","year":"2020","journal-title":"Transl. Neurodegener."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Plastini, M.J., Desu, H.L., and Brambilla, R. (2020). Dynamic Responses of Microglia in Animal Models of Multiple Sclerosis. Front. Cell Neurosci., 14.","DOI":"10.3389\/fncel.2020.00269"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e18429","DOI":"10.1016\/j.heliyon.2023.e18429","article-title":"Upregulation of EphA4 deteriorate brain damage by shifting microglia M1-polarization via NF-\u03baB signaling after focal cerebral ischemia in rats","volume":"9","author":"Wei","year":"2023","journal-title":"Heliyon"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s001150050636","article-title":"Multiple sclerosis. Current review of failed and discontinued clinical trials of drug treatment","volume":"71","author":"Wiendl","year":"2000","journal-title":"Nervenarzt"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40035-016-0054-4","article-title":"The dual roles of cytokines in Alzheimer\u2019s disease: Update on interleukins, TNF-\u03b1, TGF-\u03b2 and IFN-\u03b3","volume":"5","author":"Zheng","year":"2016","journal-title":"Transl. Neurodegener."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"a029025","DOI":"10.1101\/cshperspect.a029025","article-title":"Effector T Cells in Multiple Sclerosis","volume":"8","author":"Kaskow","year":"2018","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.bbi.2014.01.001","article-title":"Effector molecules released by Th1 but not Th17 cells drive an M1 response in microglia","volume":"37","author":"Prajeeth","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"110094","DOI":"10.1016\/j.celrep.2021.110094","article-title":"Interleukin-17 affects synaptic plasticity and cognition in an experimental model of multiple sclerosis","volume":"37","author":"Mancini","year":"2021","journal-title":"Cell Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jneuroim.2007.11.006","article-title":"Production and functions of IL-17 in microglia","volume":"194","author":"Kawanokuchi","year":"2008","journal-title":"J. Neuroimmunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10142-026-01817-z","article-title":"Unraveling the role of IL-17 signaling pathway in breast cancer-related depression: Insights from in vivo\/in vitro models and transcriptomic analysis","volume":"26","author":"Li","year":"2026","journal-title":"Funct. Integr. Genom."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Yin, J., Li, W., Shen, L.-P., Zhang, W.-L., Chen, J.-Y., Zhang, B.-B., Chen, Y.-J., Li, T., Li, H.-Z., and Gao, Z. (2026). Cerebellar microglia-derived IL-17A mitigates autism-related behavioral and synaptic deficits. Mol. Psychiatry, Online ahead of print.","DOI":"10.1038\/s41380-026-03454-1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/j.1476-5381.2011.01302.x","article-title":"Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)","volume":"164","author":"Constantinescu","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1039\/C6NP00074F","article-title":"Phytocannabinoids: A unified critical inventory","volume":"33","author":"Hanus","year":"2016","journal-title":"Nat. Prod. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1089\/can.2020.0105","article-title":"The Effects of Cannabinoids on Pro- and Anti-Inflammatory Cytokines: A Systematic Review of In Vivo Studies","volume":"6","author":"Henshaw","year":"2021","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s42238-021-00062-4","article-title":"The biosynthesis of the cannabinoids","volume":"3","author":"Tahir","year":"2021","journal-title":"J. Cannabis Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1111\/bph.15185","article-title":"A systematic review of minor phytocannabinoids with promising neuroprotective potential","volume":"177","author":"Stone","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1124\/dmd.108.020909","article-title":"Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis","volume":"36","author":"Takeda","year":"2008","journal-title":"Drug Metab. Dispos."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"627463","DOI":"10.1155\/2008\/627463","article-title":"PPAR-gamma: Therapeutic Potential for Multiple Sclerosis","volume":"2008","author":"Drew","year":"2008","journal-title":"PPAR Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1021\/acs.bioconjchem.5b00021","article-title":"Characterization of Covalent Bond Formation between PPAR\u03b3 and Oxo-Fatty Acids","volume":"26","author":"Egawa","year":"2015","journal-title":"Bioconjugate Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Miyachi, H. (2023). Structural Biology Inspired Development of a Series of Human Peroxisome Proliferator-Activated Receptor Gamma (PPAR\u03b3) Ligands: From Agonist to Antagonist. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043940"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.bbagen.2019.01.002","article-title":"Identification and characterization of phytocannabinoids as novel dual PPARalpha\/gamma agonists by a computational and in vitro experimental approach","volume":"1863","author":"Fellous","year":"2019","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1111\/bph.14019","article-title":"Tetrahydrocannabinolic acid is a potent PPARgamma agonist with neuroprotective activity","volume":"174","author":"Nadal","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s42238-026-00387-y","article-title":"Therapeutic potential of acidic cannabinoids: An update","volume":"8","author":"Singh","year":"2026","journal-title":"J. Cannabis Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1021\/acs.jnatprod.9b00600","article-title":"Pharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome","volume":"82","author":"Anderson","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8362","DOI":"10.1073\/pnas.88.19.8362","article-title":"Effects of injected Alzheimer beta-amyloid cores in rat brain","volume":"88","author":"Frautschy","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kim, J., Choi, P., Park, Y.T., Kim, T., Ham, J., and Kim, J.C. (2023). The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer\u2019s Disease-like Mouse Model. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076827"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.neurobiolaging.2007.04.019","article-title":"Increases of kinin B1 and B2 receptors binding sites after brain infusion of amyloid-beta 1\u201340 peptide in rats","volume":"29","author":"Viel","year":"2008","journal-title":"Neurobiol. Aging"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Wakshlag, J.J., Schwark, W.S., Deabold, K.A., Talsma, B.N., Cital, S., Lyubimov, A., Iqbal, A., and Zakharov, A. (2020). Pharmacokinetics of Cannabidiol, Cannabidiolic Acid, Delta9-Tetrahydrocannabinol, Tetrahydrocannabinolic Acid and Related Metabolites in Canine Serum After Dosing with Three Oral Forms of Hemp Extract. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.00505"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Azzolini, F., Gilio, L., Pavone, L., Iezzi, E., Dolcetti, E., Bruno, A., Buttari, F., Musella, A., Mandolesi, G., and Guadalupi, L. (2022). Neuroinflammation Is Associated with GFAP and sTREM2 Levels in Multiple Sclerosis. Biomolecules, 12.","DOI":"10.3390\/biom12020222"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kumar, V., Prabhu, S.D., and Bansal, S.S. (2022). CD4(+) T-lymphocytes exhibit biphasic kinetics post-myocardial infarction. Front. Cardiovasc. Med., 9.","DOI":"10.3389\/fcvm.2022.992653"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"959","DOI":"10.4049\/jimmunol.175.2.959","article-title":"Lipopolysaccharide injection induces relapses of experimental autoimmune encephalomyelitis in nontransgenic mice via bystander activation of autoreactive CD4+ cells","volume":"175","author":"Nogai","year":"2005","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.clim.2013.05.012","article-title":"Low sensitivity to glucocorticoid inhibition of in vitro Th17-related cytokine production in multiple sclerosis patients is related to elevated plasma lipopolysaccharide levels","volume":"148","author":"Teixeira","year":"2013","journal-title":"Clin. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1111\/j.1476-5381.2010.01166.x","article-title":"Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes","volume":"163","author":"Ligresti","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"20405","DOI":"10.1038\/s41598-020-77175-y","article-title":"In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa","volume":"10","author":"Zagzoog","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_46","first-page":"259","article-title":"The Beneficial Biological Properties of Salicylic Acid","volume":"32","author":"Randjelovic","year":"2015","journal-title":"Acta Fac. Medicae Naissensis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1124\/mol.63.5.983","article-title":"Activation and binding of peroxisome proliferator-activated receptor gamma by synthetic cannabinoid ajulemic acid","volume":"63","author":"Liu","year":"2003","journal-title":"Mol. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s11910-005-0051-y","article-title":"Nitric oxide and multiple sclerosis","volume":"5","author":"Encinas","year":"2005","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2008.07.008","article-title":"Regulation of autoimmune inflammation by pro-inflammatory cytokines","volume":"120","author":"Kim","year":"2008","journal-title":"Immunol. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5024","DOI":"10.4049\/jimmunol.175.8.5024","article-title":"Paradoxical anti-inflammatory actions of TNF-alpha: Inhibition of IL-12 and IL-23 via TNF receptor 1 in macrophages and dendritic cells","volume":"175","author":"Zakharova","year":"2005","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Fresegna, D., Bullitta, S., Musella, A., Rizzo, F.R., De Vito, F., Guadalupi, L., Caioli, S., Balletta, S., Sanna, K., and Dolcetti, E. (2020). Re-Examining the Role of TNF in MS Pathogenesis and Therapy. Cells, 9.","DOI":"10.3390\/cells9102290"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/cei.12209","article-title":"Blockade of tumor necrosis factor-alpha in experimental autoimmune encephalomyelitis reveals differential effects on the antigen-specific immune response and central nervous system histopathology","volume":"175","author":"Batoulis","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1084\/jem.193.4.427","article-title":"Uncoupling the proinflammatory from the immunosuppressive properties of tumor necrosis factor (TNF) at the p55 TNF receptor level: Implications for pathogenesis and therapy of autoimmune demyelination","volume":"193","author":"Kassiotis","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/nm0198-078","article-title":"TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination","volume":"4","author":"Liu","year":"1998","journal-title":"Nat. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0006-291X(05)80832-0","article-title":"Nitric oxide mediates tumor necrosis factor-alpha cytotoxicity in endothelial cells","volume":"186","author":"Estrada","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1080\/08923973.2024.2330642","article-title":"Immunopathogenesis of multiple sclerosis: Molecular and cellular mechanisms and new immunotherapeutic approaches","volume":"46","author":"Aliyu","year":"2024","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3259","DOI":"10.1007\/s00213-018-5034-1","article-title":"Effect of cannabidiolic acid and \u2206 (9)-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain","volume":"235","author":"Rock","year":"2018","journal-title":"Psychopharmacology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"106525","DOI":"10.1016\/j.eplepsyres.2020.106525","article-title":"Cannabidiolic acid exhibits entourage-like improvements of anticonvulsant activity in an acute rat model of seizures","volume":"169","author":"Goerl","year":"2021","journal-title":"Epilepsy Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"153426","DOI":"10.1016\/j.phymed.2020.153426","article-title":"\u03949-Tetrahydrocannabinolic Acid markedly alleviates liver fibrosis and inflammation in mice","volume":"81","author":"Prados","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.intimp.2005.10.002","article-title":"Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways","volume":"6","author":"Verhoeckx","year":"2006","journal-title":"Int. Immunopharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Fleisher-Berkovich, S., Ventura, Y., Amoyal, M., Dahan, A., Feinshtein, V., Alfahel, L., Israelson, A., Bernstein, N., Gorelick, J., and Ben-Shabat, S. (2023). Therapeutic Potential of Phytocannabinoid Cannabigerol for Multiple Sclerosis: Modulation of Microglial Activation In Vitro and In Vivo. Biomolecules, 13.","DOI":"10.3390\/biom13020376"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/7\/1227\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:10:57Z","timestamp":1775707857000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/7\/1227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":61,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["molecules31071227"],"URL":"https:\/\/doi.org\/10.3390\/molecules31071227","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]}}}