{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:01:11Z","timestamp":1790622071304,"version":"4.1.0"},"reference-count":48,"publisher":"The Royal Society","issue":"2","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"National Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"crossref","award":["LH2019H007"],"award-info":[{"award-number":["LH2019H007"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81773458"],"award-info":[{"award-number":["81773458"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81903348"],"award-info":[{"award-number":["81903348"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:p>\n                    Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system\u2014endogenous cannabinoids, their receptors and associated enzymes\u2014in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    , which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.\n                  <\/jats:p>","DOI":"10.1098\/rsob.200306","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T19:12:28Z","timestamp":1612293148000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":57,"title":["Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder"],"prefix":"10.1098","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7521-2388","authenticated-orcid":true,"given":"Mingyang","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dexin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Children Psychology, Zhuhai Maternal and Child Health Care Hospital, Zhuhai 519001, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Office of Leading Group for Control and Prevention of Major Diseases and Infectious diseases, Dezhou Center for Disease Control and Prevention, Dezhou 253011, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1798-0768","authenticated-orcid":true,"given":"Caihong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0631-5076","authenticated-orcid":true,"given":"Lijie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Children's and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association","year":"2013","unstructured":"American Psychiatric Association. 2013 Diagnostic and statistical manual of mental disorders, pp. 58-62. 5th edn. Washington, DC: American Psychiatric Association.","edition":"5"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-018-0246-0"},{"key":"e_1_3_7_4_2","first-page":"1","article-title":"Prevalence of autism spectrum disorder among children aged 8 years: autism and developmental disabilities monitoring network, 11 sites, United States, 2016","volume":"69","author":"Maenner MJ","year":"2020","unstructured":"Maenner MJ et al. 2020 Prevalence of autism spectrum disorder among children aged 8 years: autism and developmental disabilities monitoring network, 11 sites, United States, 2016. Morb. Mortal. Wkly Rep. Surveill. Summ. 69, 1-12. (doi:10.15585\/mmwr.ss6904a1)","journal-title":"Morb. Mortal. Wkly Rep. Surveill. Summ."},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2007.11.006"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2019.03.002"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-018-0203-y"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-019-0256-6"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-013-1824-9"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-78"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2045"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2013.04.043"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14435"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00367"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2013.09.003"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/can.2015.0008"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107736"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2616"},{"key":"e_1_3_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.221"},{"key":"e_1_3_7_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI131752"},{"key":"e_1_3_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.01.012"},{"key":"e_1_3_7_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-017-4805-4"},{"key":"e_1_3_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.083"},{"key":"e_1_3_7_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14473"},{"key":"e_1_3_7_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo9030042"},{"key":"e_1_3_7_26_2","first-page":"325061","article-title":"Beneficial effects of palmitoylethanolamide on expressive language, cognition, and behaviors in autism: a report of two cases","volume":"2015","author":"Antonucci N","year":"2015","unstructured":"Antonucci N, Cirillo A, Siniscalco D. 2015 Beneficial effects of palmitoylethanolamide on expressive language, cognition, and behaviors in autism: a report of two cases. Case Rep. Psychiatry 2015, 325061. (doi:10.1155\/2015\/325061)","journal-title":"Case Rep. Psychiatry"},{"key":"e_1_3_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2018.04.022"},{"key":"e_1_3_7_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37570-y"},{"key":"e_1_3_7_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-018-3808-2"},{"key":"e_1_3_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2012.04.011"},{"key":"e_1_3_7_31_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509795112"},{"key":"e_1_3_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2012.06.009"},{"key":"e_1_3_7_33_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00424"},{"key":"e_1_3_7_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.169"},{"key":"e_1_3_7_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2019.109666"},{"key":"e_1_3_7_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187926"},{"key":"e_1_3_7_37_2","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-2-10"},{"key":"e_1_3_7_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23317"},{"key":"e_1_3_7_39_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161208785740018"},{"key":"e_1_3_7_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.61"},{"key":"e_1_3_7_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.07.152"},{"key":"e_1_3_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2015.03.033"},{"key":"e_1_3_7_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.182"},{"key":"e_1_3_7_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02237.x"},{"key":"e_1_3_7_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1209200"},{"key":"e_1_3_7_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-019-1596-0"},{"key":"e_1_3_7_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12411"},{"key":"e_1_3_7_48_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23123167"},{"key":"e_1_3_7_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2011.00064"}],"container-title":["Open Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.200306","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsob.200306","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.200306","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T09:10:26Z","timestamp":1669626626000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsob.200306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2]]},"references-count":48,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,2]]}},"alternative-id":["10.1098\/rsob.200306"],"URL":"https:\/\/doi.org\/10.1098\/rsob.200306","relation":{"has-review":[{"id-type":"doi","id":"10.1098\/RSOB.200306\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.200306\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.200306\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.200306\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.200306\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.200306\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.200306\/v3\/decision1","asserted-by":"object"}]},"ISSN":["2046-2441"],"issn-type":[{"value":"2046-2441","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2]]},"assertion":[{"value":"2020-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"200306"}}