{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:06:38Z","timestamp":1792785998735,"version":"4.5.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oxford Health Clinical Research Facility"},{"DOI":"10.13039\/100030827","name":"NHS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100030827","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Health and Social Care in the United Kingdom","id":[{"id":"https:\/\/ror.org\/03sbpja79","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Over 120 phytocannabinoids and 190 synthetic and semi-synthetic cannabinoids have been identified. Many of these currently circulate in recreational and illicit drug markets. Epidemiological evidence indicates a progressive increase in their use but long-term effects of cannabinoids on the CNS remain poorly understood. Exogenous cannabinoids can interact with cannabinoid receptor CB2, which is expressed on astrocytes and microglia, the key regulators of neuroinflammatory responses. Dysregulated or chronic microglial activation can sustain neuroinflammation, a central mechanism underlying neurodegenerative diseases. Clarifying cannabinoid-induced alterations in glia is therefore crucial both because their widespread consumption and the global burden of neurodegenerative disorders, for which cannabinoids might offer therapeutic potential. This review was conducted by a multidisciplinary team following JBI and PRISMA-ScR guidelines that systematically mapped available evidence across PubMed, Scopus and Web of Science. The findings are thematically organized and qualitatively summarized and indicate compound and time-dependent effects. Acute exposure appears to be neuroprotective whereas chronic effects remain unclear. Preliminary data suggest that some synthetic and semi-synthetic cannabinoids may retain protective actions while \u03949-tetrahydrocannabinol (THC) may promote glial activation and neuroinflammation, These results underscore the need for further in vivo and longitudinal studies to evaluate long-term impacts and inform safe therapeutic and regulatory strategies.<\/jats:p>","DOI":"10.1093\/jnen\/nlag049","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T11:21:40Z","timestamp":1776684100000},"page":"1063-1081","source":"Crossref","is-referenced-by-count":0,"title":["Effects of phytocannabinoids, synthetic and semi-synthetic cannabinoids on microglia and astrocytes: Review of neuroinflammatory mechanisms"],"prefix":"10.1093","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9598-4282","authenticated-orcid":false,"given":"Giulia","family":"Brambilla","sequence":"first","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia , Pavia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Belli","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia , Pavia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Paggi","sequence":"additional","affiliation":[{"name":"Oxford Health NHS Foundation Trust , Oxford,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Morini","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia , Pavia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Damiana","family":"Vison\u00e0","sequence":"additional","affiliation":[{"name":"Department of Public Health, Experimental and Forensic Medicine, University of Pavia , Pavia,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"2026092503320703800_nlag049-B1","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.phrs.2016.07.008","article-title":"Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats","volume":"111","author":"Zamberletti","year":"2016","journal-title":"Pharmacol Res"},{"key":"2026092503320703800_nlag049-B2","author":"World Drug Report","year":"2025"},{"key":"2026092503320703800_nlag049-B3","author":"Routes of Marijuana Use\u2013Behavioral Risk Factor Surveillance System","year":"2025"},{"key":"2026092503320703800_nlag049-B4","author":"Monitoring the Future [National Institute on Drug Abuse Web Site]","year":"2026"},{"key":"2026092503320703800_nlag049-B5","author":"European Drug Report","year":"2023"},{"key":"2026092503320703800_nlag049-B6","author":"Cannabis Potency Data [National Institute on Drug Abuse Web Site]","year":"2024"},{"key":"2026092503320703800_nlag049-B7","author":"New psychoactive substances\u2013the current situation in Europe","year":"2025"},{"key":"2026092503320703800_nlag049-B8","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3390\/brainsci8030040","article-title":"The effects of cannabinoids on executive functions: evidence from cannabis and synthetic cannabinoids-a systematic review","volume":"8","author":"Cohen","year":"2018","journal-title":"Brain Sci"},{"key":"2026092503320703800_nlag049-B9","year":"2026"},{"key":"2026092503320703800_nlag049-B10","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1152\/physrev.00019.2008","article-title":"Endocannabinoid-mediated control of synaptic transmission","volume":"89","author":"Kano","year":"2009","journal-title":"Physiol Rev"},{"key":"2026092503320703800_nlag049-B11","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/365061a0","article-title":"Molecular characterization of a peripheral receptor for cannabinoids","volume":"365","author":"Munro","year":"1993","journal-title":"Nature"},{"key":"2026092503320703800_nlag049-B12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1126\/science.1115740","article-title":"Identification and functional characterization of brainstem cannabinoid CB2 receptors","volume":"310","author":"Van Sickle","year":"2005","journal-title":"Science"},{"key":"2026092503320703800_nlag049-B13","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1471-4159.2005.03380.x","article-title":"Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli","volume":"95","author":"Maresz","year":"2005","journal-title":"J Neurochem"},{"key":"2026092503320703800_nlag049-B14","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1002\/glia.23247","article-title":"Epilepsy and astrocyte energy metabolism","volume":"66","author":"Boison","year":"2018","journal-title":"Glia"},{"key":"2026092503320703800_nlag049-B15","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.3389\/fphys.2019.01531","article-title":"Cellular specificity and inter-cellular coordination in the brain bioenergetic system: implications for aging and neurodegeneration","volume":"10","author":"Qi","year":"2019","journal-title":"Front Physiol"},{"key":"2026092503320703800_nlag049-B16","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1515\/REVNEURO.2002.13.3.221","article-title":"Reciprocal interactions between microglia and neurons: from survival to neuropathology","volume":"13","author":"Polazzi","year":"2002","journal-title":"Rev Neurosci"},{"key":"2026092503320703800_nlag049-B17","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s11481-015-9592-2","article-title":"Exposure of adolescent mice to Delta-9-tetrahydrocannabinol induces long-lasting modulation of pro- and anti-inflammatory cytokines in hypothalamus and hippocampus similar to that observed for peripheral macrophages","volume":"10","author":"Moretti","year":"2015","journal-title":"J Neuroimmune Pharmacol"},{"key":"2026092503320703800_nlag049-B18","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0165-0173(94)00015-H","article-title":"Microglia: intrinsic immuneffector cell of the brain","volume":"20","author":"Gehrmann","year":"1995","journal-title":"Brain Res Brain Res Rev"},{"key":"2026092503320703800_nlag049-B19","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":"2026092503320703800_nlag049-B20","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1046\/j.1365-2990.1998.00131.x","article-title":"Identification of glial cell proliferation in early multiple sclerosis lesions","volume":"24","author":"Sch\u00f6nrock","year":"1998","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2026092503320703800_nlag049-B21","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/0197-4580(95)00092-S","article-title":"Role of microglia in senile plaque formation","volume":"16","author":"Mackenzie","year":"1995","journal-title":"Neurobiol Aging"},{"key":"2026092503320703800_nlag049-B22","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/jlb.56.3.387","article-title":"Macrophages\/microglia and the pathophysiology of CNS injuries in AIDS","volume":"56","author":"Gendelman","year":"1994","journal-title":"J Leukoc Biol"},{"key":"2026092503320703800_nlag049-B23","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1080\/078538902321117698","article-title":"Microglia in diseases of the central nervous system","volume":"34","author":"Nelson","year":"2002","journal-title":"Ann Med"},{"key":"2026092503320703800_nlag049-B24","author":"Number of people with MS [MS international Federation Web Site]","year":"2026"},{"key":"2026092503320703800_nlag049-B25","author":"Dementia [World Health Organization Web Site]","year":"2025"},{"key":"2026092503320703800_nlag049-B26","doi-asserted-by":"crossref","first-page":"e70009","DOI":"10.1002\/alz.70009","article-title":"Dementia prevalence and risk factors in people with and without HIV in Malawi: a medical record review","volume":"21","author":"Lee","year":"2025","journal-title":"Alzheimers Dement J Alzheimers Assoc"},{"key":"2026092503320703800_nlag049-B27","author":"People with HIV","year":"2023"},{"key":"2026092503320703800_nlag049-B28","doi-asserted-by":"crossref","first-page":"3575","DOI":"10.3390\/ijms21103575","article-title":"Antioxidant and neuroprotective effects induced by cannabidiol and cannabigerol in rat CTX-TNA2 astrocytes and isolated cortexes","volume":"21","author":"di Giacomo","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026092503320703800_nlag049-B29","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1172\/JCI67569","article-title":"Microglial activation underlies cerebellar deficits produced by repeated cannabis exposure","volume":"123","author":"Cutando","year":"2013","journal-title":"J Clin Invest"},{"key":"2026092503320703800_nlag049-B30","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1515\/jbcpp-2015-0071","article-title":"Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol - studies in BV-2 microglia and encephalitogenic T cells","volume":"27","author":"Juknat","year":"2016","journal-title":"J Basic Clin Physiol Pharmacol"},{"key":"2026092503320703800_nlag049-B31","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/glia.10177","article-title":"Cannabinoids ablate release of TNFalpha in rat microglial cells stimulated with lypopolysaccharide","volume":"41","author":"Facchinetti","year":"2003","journal-title":"Glia"},{"key":"2026092503320703800_nlag049-B32","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1007\/s12640-021-00369-3","article-title":"MAM-2201, one of the most potent-naphthoyl indole derivative-synthetic cannabinoids, exerts toxic effects on human cell-based models of neurons and astrocytes","volume":"39","author":"Coccini","year":"2021","journal-title":"Neurotox Res"},{"key":"2026092503320703800_nlag049-B33","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1124\/jpet.119.260661","article-title":"\u03949-tetrahydrocannabinol suppresses monocyte-mediated astrocyte production of monocyte chemoattractant protein 1 and interleukin-6 in a toll-like receptor 7-stimulated human coculture","volume":"371","author":"Rizzo","year":"2019","journal-title":"J Pharmacol Exp Ther"},{"key":"2026092503320703800_nlag049-B34","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.3390\/ijms24021421","article-title":"Human astrocyte spheroids as suitable in vitro screening model to evaluate synthetic cannabinoid MAM2201-induced effects on CNS","volume":"24","author":"De Simone","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026092503320703800_nlag049-B35","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3390\/toxics10020048","article-title":"Neuronal and astrocytic morphological alterations driven by prolonged exposure with \u03949-tetrahydrocannabinol but not cannabidiol","volume":"10","author":"Landucci","year":"2022","journal-title":"Toxics"},{"key":"2026092503320703800_nlag049-B36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1742-2094-2-29","article-title":"Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation","volume":"2","author":"Ehrhart","year":"2005","journal-title":"J Neuroinflammation"},{"key":"2026092503320703800_nlag049-B37","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3390\/ijms20030507","article-title":"Cannabisin F from hemp (Cannabis sativa) seed suppresses lipopolysaccharide-induced inflammatory responses in BV2 microglia as SIRT1 modulator","volume":"20","author":"Wang","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026092503320703800_nlag049-B38","doi-asserted-by":"crossref","first-page":"578325","DOI":"10.1016\/j.jneuroim.2024.578325","article-title":"Immune and glial cell alterations in the rat brain after repeated exposure to the synthetic cannabinoid JWH-018","volume":"389","author":"Pintori","year":"2024","journal-title":"J Neuroimmunol"},{"key":"2026092503320703800_nlag049-B39","doi-asserted-by":"crossref","first-page":"100573","DOI":"10.1016\/j.phyplu.2024.100573","article-title":"The phenylpropionamide extract of hemp (Cannabis sativa L.) seed improves learning memory ability and survival rate by attenuating microglia activation and reducing amyloid deposition via the SIRT1-AMAD10 pathway in APP\/PS1 mice","volume":"4","author":"Yang","year":"2024","journal-title":"Phytomedicine Plus"},{"key":"2026092503320703800_nlag049-B40","doi-asserted-by":"crossref","first-page":"105769","DOI":"10.1016\/j.neuint.2024.105769","article-title":"Cannabidiol prevents LPS-induced inflammation by inhibiting the NLRP3 inflammasome and iNOS activity in BV2 microglia cells via CB2 receptors and PPAR\u03b3","volume":"177","author":"Rodrigues","year":"2024","journal-title":"Neurochem Int"},{"key":"2026092503320703800_nlag049-B41","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1002\/glia.24489","article-title":"The two synthetic cannabinoid compounds 4\u2019-F-CBD and HU-910 efficiently restrain inflammatory responses of brain microglia and astrocytes","volume":"72","author":"Dos Santos Pereira","year":"2024","journal-title":"Glia"},{"key":"2026092503320703800_nlag049-B42","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bbi.2022.06.011","article-title":"Synthetic cannabinoids reduce the inflammatory activity of microglia and subsequently improve neuronal survival in vitro","volume":"105","author":"Young","year":"2022","journal-title":"Brain Behav Immun"},{"key":"2026092503320703800_nlag049-B43","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1002\/ptr.7458","article-title":"Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-\u03baB-mediated signaling","volume":"36","author":"Borgonetti","year":"2022","journal-title":"Phytother Res"},{"key":"2026092503320703800_nlag049-B44","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s11481-020-09912-z","article-title":"\u03949-tetrahydrocannabinol (THC) impairs CD8+ T cell-mediated activation of astrocytes","volume":"15","author":"Henriquez","year":"2020","journal-title":"J Neuroimmune Pharmacol"},{"key":"2026092503320703800_nlag049-B45","doi-asserted-by":"crossref","first-page":"e0251677","DOI":"10.1371\/journal.pone.0251677","article-title":"Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia","volume":"16","author":"Wu","year":"2021","journal-title":"PLoS One"},{"key":"2026092503320703800_nlag049-B46","first-page":"496","article-title":"Abnormal cannabidiol affects production of pro-inflammatory mediators and astrocyte wound closure in primary astrocytic-microglial cocultures","volume":"25","author":"Cardinal von Widdern","year":"2020","journal-title":"Mol Basel Switz"},{"key":"2026092503320703800_nlag049-B47","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/glia.23738","article-title":"Cannabidiol prevents LPS-induced microglial inflammation by inhibiting ROS\/NF-\u03baB-dependent signaling and glucose consumption","volume":"68","author":"Dos-Santos-Pereira","year":"2020","journal-title":"Glia"},{"key":"2026092503320703800_nlag049-B48","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.brainres.2012.02.058","article-title":"Cannabinoids prevent lipopolysaccharide-induced neurodegeneration in the rat substantia nigra in vivo through inhibition of microglial activation and NADPH oxidase","volume":"1451","author":"Chung","year":"2012","journal-title":"Brain Res"},{"key":"2026092503320703800_nlag049-B49","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1254\/jphs.12170FP","article-title":"Anti-neuroinflammatory activity of a novel cannabinoid derivative by inhibiting the NF-\u03baB signaling pathway in lipopolysaccharide-induced BV-2 microglial cells","volume":"121","author":"More","year":"2013","journal-title":"J Pharmacol Sci"},{"key":"2026092503320703800_nlag049-B50","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1111\/j.1471-4159.2009.06407.x","article-title":"Cannabinoids prevent the opposite regulation of astroglial connexin43 hemichannels and gap junction channels induced by pro-inflammatory treatments","volume":"111","author":"Froger","year":"2009","journal-title":"J Neurochem"},{"key":"2026092503320703800_nlag049-B51","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1742-2094-9-8","article-title":"Prolonged oral cannabinoid administration prevents neuroinflammation, lowers \u03b2-amyloid levels and improves cognitive performance in Tg APP 2576 mice","volume":"9","author":"Mart\u00edn-Moreno","year":"2012","journal-title":"J Neuroinflammation"},{"key":"2026092503320703800_nlag049-B52","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1111\/j.1476-5381.2011.01379.x","article-title":"Cannabidiol inhibits pathogenic T cells, decreases spinal microglial activation and ameliorates multiple sclerosis-like disease in C57BL\/6 mice","volume":"163","author":"Kozela","year":"2011","journal-title":"Br J Pharmacol"},{"key":"2026092503320703800_nlag049-B53","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10571-013-9984-x","article-title":"Cannabinoid effects on \u03b2 amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro","volume":"34","author":"Janefjord","year":"2014","journal-title":"Cell Mol Neurobiol"},{"key":"2026092503320703800_nlag049-B54","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1007\/s11481-012-9399-3","article-title":"A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis","volume":"7","author":"Granja","year":"2012","journal-title":"J Neuroimmune Pharmacol"},{"key":"2026092503320703800_nlag049-B55","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.nbd.2009.01.014","article-title":"Cannabinoids attenuate the effects of aging upon neuroinflammation and neurogenesis","volume":"34","author":"Marchalant","year":"2009","journal-title":"Neurobiol Dis"},{"key":"2026092503320703800_nlag049-B56","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: a field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"}],"container-title":["Journal of Neuropathology &amp; Experimental Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/85\/10\/1063\/68293707\/nlag049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnen\/article-pdf\/85\/10\/1063\/68293707\/nlag049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T07:32:18Z","timestamp":1790321538000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnen\/article\/85\/10\/1063\/8679007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5,15]]},"published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jnen\/nlag049","relation":{},"ISSN":["0022-3069","1554-6578"],"issn-type":[{"value":"0022-3069","type":"print"},{"value":"1554-6578","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,5,15]]}}}