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However, the safety issue of CBD in the nervous system has not been settled fully, while CBD has been reported to have mild side effects including dizziness and somnolence. In this work, a platform of neuron\u2010astrocyte sandwich coculture to investigate the neurotoxicity of CBD, as well as the neuronal responses to CBD, in a more in vivo relevant mode is constructed. CBD (15 and 30\u00a0\u00b5<jats:sc>m<\/jats:sc>) causes the viability decrease, along with morphological damage, in the neuron\u2010alone culture, whereas its neurotoxic effects are significantly attenuated by the supports of astrocytes in the neuron\u2010astrocyte coculture. In addition, it is found that CBD\u2010induced increase of intracellular Ca<jats:sup>2+<\/jats:sup> concentration and depolarization of mitochondrial membrane potential, via activation of transient receptor potential vanilloid 1, are noticeably ameliorated by coculturing neurons with astrocytes. This work provides crucial information in the development of CBD as therapeutics for neurological disorders, as well as in a fundamental understanding of how CBD works in the nervous system.<\/jats:p>","DOI":"10.1002\/adbi.202300090","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T22:55:05Z","timestamp":1682031305000},"source":"Crossref","is-referenced-by-count":4,"title":["Neutralization of Cannabidiol Neurotoxicity in Neuron\u2010Astrocyte Sandwich Coculture"],"prefix":"10.1002","volume":"7","author":[{"given":"Jungnam","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Chemistry KAIST  Daejeon 34141 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seoin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry KAIST  Daejeon 34141 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-673X","authenticated-orcid":false,"given":"Insung S.","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Chemistry KAIST  Daejeon 34141 South Korea"},{"name":"Department of Bio and Brain Engineering KAIST  Daejeon 34141 South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-5949.2008.00065.x"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.2625"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00124"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology11060817"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2021.2024493"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26196077"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611618"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714631"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13499"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/can.2019.0102"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-020-00277-y"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9020135"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-84879-2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms150610034"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21044"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins14100720"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00783-4"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00390-x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-08-02553.1996"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(199911)28:2<85::AID-GLIA1>3.0.CO;2-Y"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11596-O"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00050-1"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1999.0751"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.001"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.10035"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145708009024"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13193"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.11.016"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.7b00300"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419683112"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/asia.201800996"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.7551\/mitpress\/4913.001.0001"},{"key":"e_1_2_8_33_1","first-page":"209","volume":"4","author":"Wang X. 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