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Studies evaluating the impact of cannabinoids (agonists or antagonists) on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic SCI were included. Data extracted from relevant studies, included sample characteristics, injury model, neurobehavioural outcomes assessed and study results. PRISMA guidelines were followed and the SYRCLE checklist was used to assess risk of bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The search returned 8714 studies, 19 of which met our inclusion criteria. Sample sizes ranged from 23 to 390 animals. WIN 55,212-2 (<jats:italic>n<\/jats:italic>\u2009=\u20096) and AM 630 (<jats:italic>n<\/jats:italic>\u2009=\u20098) were the most used cannabinoid receptor agonist and antagonist respectively. Acute SCI models included traumatic injury (<jats:italic>n<\/jats:italic>\u2009=\u200916), ischaemia\/reperfusion injury (<jats:italic>n<\/jats:italic>\u2009=\u20092), spinal cord cryoinjury (<jats:italic>n<\/jats:italic>\u2009=\u20091) and spinal cord ischaemia (<jats:italic>n<\/jats:italic>\u2009=\u20091). Assessment tools used assessed locomotor function, pain and anxiety. Cannabinoid receptor agonists resulted in statistically significant improvement in locomotor function in 9 out of 10 studies and pain outcomes in 6 out of 6 studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Modulation of the endo-cannabinoid system has demonstrated significant improvement in both pain and locomotor function in pre-clinical SCI models; however, the risk of bias is unclear in all studies. These results may help to contextualise future translational clinical trials investigating whether cannabinoids can improve pain and locomotor function in SCI patients.<\/jats:p><\/jats:sec>","DOI":"10.1038\/s41393-021-00680-y","type":"journal-article","created":{"date-parts":[[2021,8,14]],"date-time":"2021-08-14T17:02:39Z","timestamp":1628960559000},"page":"1221-1239","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Systematic review of the impact of cannabinoids on neurobehavioral outcomes in preclinical models of traumatic and nontraumatic spinal cord injury"],"prefix":"10.1038","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3897-4196","authenticated-orcid":false,"given":"Faheem I.","family":"Bhatti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver D.","family":"Mowforth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2536-0534","authenticated-orcid":false,"given":"Max B.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniqah I.","family":"Bhatti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylva","family":"Adeeko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melika","family":"Akhbari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Dilworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8839-4718","authenticated-orcid":false,"given":"Ben","family":"Grodzinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Temidayo","family":"Osunronbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Ottewell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0286-2953","authenticated-orcid":false,"given":"Jye Quan","family":"Teh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayathri","family":"Suresh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Unaiza","family":"Waheed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benn","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2879-4020","authenticated-orcid":false,"given":"Isla","family":"Kuhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2019-8125","authenticated-orcid":false,"given":"Richard D.","family":"Bartlett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin M.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5145-7199","authenticated-orcid":false,"given":"Mark R. 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(Arevalo-Martin, Garcia-Ovejero, Gomez, Rubio-Araiz, Navarro-Galve, Molina-Holgado) Laboratory of Neuroinflammation, Unidad de Neurologia Experimental, Hospital Nacional de Paraplejicos (SESCAM), 45071 Toledo, Spain (Arevalo-Martin, Garcia-Ovejero, Gomez. https:\/\/ovidsp.ovid.com\/athens\/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med6&AN=17891163, https:\/\/cambridge-primo.hosted.exlibrisgroup.com\/openurl\/44CAM\/44CAM_services_page?sid=OVID:medline&id=pmid:17891163&id=doi:10.1038%2Fsj.bjp.0707466&issn=0007-1.","DOI":"10.1038\/sj.bjp.0707466"},{"key":"680_CR21","doi-asserted-by":"crossref","unstructured":"Fernandez-Lopez D, Pradillo JM, Garcia-Yebenes I, Martinez-Orgado JA, Moro MA, Lizasoain I. The cannabinoid WIN55212-2 promotes neural repair after neonatal hypoxia-ischemia. Stroke. 2010;41:2956\u201364. 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Faculty of Medicine, School of Optometry, Universite de Montreal, Montreal, Quebec, Canada. Bouchard, Jean-Francois. Faculty of Medicine, Sc. https:\/\/ovidsp.ovid.com\/athens\/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med10&AN=24148808, https:\/\/cambridge-primo.hosted.exlibrisgroup.com\/openurl\/44CAM\/44CAM_services_page?sid=OVID:medline&id=pmid:24148808&id=doi:10.1016%2Fj.neuropharm.2013.10.006&.","DOI":"10.1016\/j.neuropharm.2013.10.006"},{"key":"680_CR23","doi-asserted-by":"publisher","first-page":"402","DOI":"10.2174\/1570159X18666200420085712","volume":"19","author":"KJ Nabata","year":"2021","unstructured":"Nabata KJ, Tse EK, Nightingale TE, Lee AHX, Eng JJ, Quer\u00e9e M. et al. The therapeutic potential and usage patterns of cannabinoids in people with spinal cord injuries: a systematic review. 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