{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:24:29Z","timestamp":1787509469639,"version":"build-2736575974"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T00:00:00Z","timestamp":1664755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/50891-1 2020\/12110-9"],"award-info":[{"award-number":["2014\/50891-1 2020\/12110-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007762","name":"Instituto Nacional de Ci\u00eancia e Tecnologia Translacional em Medicina","doi-asserted-by":"publisher","award":["2008\/09009-2"],"award-info":[{"award-number":["2008\/09009-2"]}],"id":[{"id":"10.13039\/501100007762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["401058\/2020-4 465458\/2014-9"],"award-info":[{"award-number":["401058\/2020-4 465458\/2014-9"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    To assess whether the effects of oral administration of 300\u00a0mg of Cannabidiol (CBD) for 28\u00a0days on mental health are maintained for a period after the medication discontinuation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    This is a 3-month follow-up observational and clinical trial study. The data were obtained from two studies performed simultaneously by the same team in the same period and region with Brazilian frontline healthcare workers during the COVID-19 pandemic. Scales to assess emotional symptoms were applied weekly, in the first month, and at weeks eight and 12.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The primary outcome was that, compared to the control group, a significant reduction in General Anxiety Disorder-7 Questionnaire (GAD-7) from baseline values was observed in the CBD group on weeks two, four, and eight (Within-Subjects Contrasts, time-group interactions: F\n                    <jats:sub>1-125<\/jats:sub>\n                    = 7.67;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.006; \u03b7\n                    <jats:sub>p<\/jats:sub>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.06; F\n                    <jats:sub>1-125<\/jats:sub>\n                    = 6.58;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.01; \u03b7\n                    <jats:sub>p<\/jats:sub>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.05; F\n                    <jats:sub>1-125<\/jats:sub>\n                    = 4.28;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.04; \u03b7\n                    <jats:sub>p<\/jats:sub>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.03, respectively) after the end of the treatment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    The anxiolytic effects of CBD in frontline health care professionals during the COVID-19 pandemic were maintained up to 1\u00a0month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings and weigh the benefits of CBD therapy against potential undesired or adverse effects.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.856846","type":"journal-article","created":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T01:30:44Z","timestamp":1664760644000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Maintained anxiolytic effects of cannabidiol after treatment discontinuation in healthcare workers during the COVID-19 pandemic"],"prefix":"10.3389","volume":"13","author":[{"given":"Jos\u00e9 Diogo S.","family":"Souza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio W.","family":"Zuardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco S.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1via de Lima","family":"Os\u00f3rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia Regina","family":"Loureiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alline Cristina","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime E. C.","family":"Hallak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael G.","family":"Dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella Lara","family":"Machado Silveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Pereira-Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Cozar","family":"Pacheco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Mayumi","family":"Ushirohira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Rinaldi","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla Cristinne Mancini","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davi Silveira","family":"Scomparin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franciele Franco","family":"Scarante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabela","family":"Pires-Dos-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Mechoulam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1vio","family":"Kapczinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedito A. L.","family":"Fonseca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danillo L. A.","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maristela Haddad","family":"Andraus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Alexandre S.","family":"Crippa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3109\/13651501.2012.667114","article-title":"Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care","volume":"16","author":"Bandelow","year":"2012","journal-title":"Int. J. Psychiatry Clin. Pract."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1038\/npp.2011.6","article-title":"Cannabidiol reduces the anxiety induced by simulated public speaking in treatment na\u00efve social phobia patients","volume":"36","author":"Bergamaschi","year":"2011","journal-title":"Neuropsychopharmacology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"237","DOI":"10.2174\/157488611798280924","article-title":"Safety and side effects of cannabidiol, a Cannabis sativa constituent","volume":"6","author":"Bergamaschi","year":"2011","journal-title":"Curr. Drug Saf."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1007\/s00213-021-06043-y","article-title":"Effects of cannabidiol on symptoms induced by the recall of traumatic events in patients with posttraumatic stress disorder","volume":"239","author":"Bolsoni","year":"2022","journal-title":"Psychopharmacology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1111\/bcp.13703","article-title":"Clinical issues in cannabis use","volume":"84","author":"Bonomo","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1016\/j.jpsychires.2012.08.012","article-title":"Cannabidiol blocks long lasting behavioral consequences of predator threat stress: Possible involvement of 5HT1A receptors","volume":"46","author":"Campos","year":"2012","journal-title":"J. Psychiatr. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1016\/j.pnpbp.2009.08.017","article-title":"Evidence for a potential role for TRPV1 receptors in the dorsolateral periaqueductal gray in the attenuation of the anxiolytic effects of cannabinoids","volume":"33","author":"Campos","year":"2009","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1590\/S0103-166X2007000300004","article-title":"Artigo parcialmente retratado: Propriedades psicom\u00e9tricas do Maslach burnout inventory em uma amostra multifuncional","volume":"24","author":"Carlotto","year":"2007","journal-title":"Estud. Psicol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1177\/0269881110379283","article-title":"Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report","volume":"25","author":"Crippa","year":"2011","journal-title":"J. Psychopharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.3389\/fimmu.2018.02009","article-title":"Translational investigation of the therapeutic potential of cannabidiol (CBD): Toward a new age","volume":"21","author":"Crippa","year":"2018","journal-title":"Front. Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e2120603","DOI":"10.1001\/jamanetworkopen.2021.20603","article-title":"Efficacy and safety of cannabidiol plus standard care vs standard care alone for the treatment of emotional exhaustion and burnout among frontline health care workers during the COVID-19 pandemic: A randomized clinical trial","volume":"4","author":"Crippa","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"B12","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1007\/s00213-012-2955-y","article-title":"Cannabidiol enhances consolidation of explicit fear extinction in humans","volume":"226","author":"Das","year":"2013","journal-title":"Psychopharmacology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1111\/j.1744-6163.2009.00224.x","article-title":"Study of the discriminative validity of the PHQ-9 and PHQ-2 in a sample of Brazilian women in the context of primary health care","volume":"45","author":"de Lima Os\u00f3rio","year":"2009","journal-title":"Perspect. Psychiatric Care"},{"key":"B14","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1007\/BF02244012","article-title":"Antianxiety effect of cannabidiol in the elevated plus-maze","volume":"100","author":"Guimar\u00e3es","year":"1990","journal-title":"Psychopharmacology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1001\/jamapsychiatry.2017.0724","article-title":"US adult illicit cannabis use, cannabis use disorder, and medical marijuana laws: 1991-1992 to 2012-2013","volume":"74","author":"Hasin","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"B16","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1365-2125.2012.04418.x","article-title":"Benzodiazepine harm: How can it be reduced?","volume":"77","author":"Lader","year":"2014","journal-title":"Br. J. Clin. Pharmacol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e2020977","DOI":"10.1001\/jamanetworkopen.2020.20977","article-title":"Self-reported cannabidiol (CBD) use for conditions with proven therapies","volume":"3","author":"Leas","year":"2020","journal-title":"JAMA Netw. Open"},{"key":"B18","doi-asserted-by":"publisher","first-page":"S617","DOI":"10.1016\/S0924-977X(16)31702-3","article-title":"Cannabidiol presents an inverted U-shaped dose-response curve in the simulated public speaking test","volume":"26","author":"Linares","year":"2018","journal-title":"Eur. Neuropsychopharmacol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1600-0447.1987.tb10566.x","article-title":"The UKU side effect rating scale: A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients","volume":"334","author":"Lingjaerde","year":"1987","journal-title":"Acta Psychiatr. Scand. Suppl."},{"key":"B20","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.drugalcdep.2016.10.004","article-title":"State-level medical marijuana laws, marijuana use and perceived availability of marijuana among the general U.S. population","volume":"169","author":"Martins","year":"2016","journal-title":"Drug Alcohol Depend."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.3389\/fpsyg.2019.02466","article-title":"Anxiolytic effects of repeated cannabidiol treatment in teenagers with social anxiety disorders","volume":"10","author":"Masataka","year":"2019","journal-title":"Front. Psychol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.3389\/fphar.2018.01365","article-title":"A systematic review on the Pharmacokinetics of cannabidiol in Humans","volume":"9","author":"Millar","year":"2018","journal-title":"Front. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1016\/j.pnpbp.2006.06.004","article-title":"Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test","volume":"30","author":"Moreira","year":"2006","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B24","doi-asserted-by":"publisher","first-page":"367","DOI":"10.9788\/tp2016.1-25","article-title":"Factor structure, reliability, and item parameters of the Brazilian-Portuguese version of the GAD-7 questionnaire","volume":"24","author":"Moreno","year":"2016","journal-title":"Temas Psicol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1590\/S1516-44461999000500006","article-title":"Psicofarmacologia de antidepressivos","volume":"21","author":"Moreno","year":"1999","journal-title":"Braz. J. Psychiatry."},{"key":"B26","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1590\/0101-60830000000107","article-title":"Posttraumatic stress disorder checklist for DSM-5 (PCL-5): Transcultural adaptation of the Brazilian version","volume":"44","author":"Os\u00f3rio","year":"2017","journal-title":"Archives Clin. Psychiatry"},{"key":"B27","doi-asserted-by":"publisher","first-page":"662742","DOI":"10.3389\/fpsyt.2021.662742","article-title":"Risk and protective factors for the mental health of Brazilian healthcare workers in the frontline of COVID-19 pandemic","volume":"12","author":"Os\u00f3rio","year":"2021","journal-title":"Front. Psychiatry"},{"key":"B28","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1097\/JCP.0000000000001405","article-title":"Cannabidiol as a treatment for mental health OutcomesAmong health care workers during the coronavirus disease pandemic","volume":"41","author":"Pacheco","year":"2021","journal-title":"J. Clin. Psychopharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"110247","DOI":"10.1016\/j.pnpbp.2021.110247","article-title":"The prevalence of anxiety and depression among healthcare workers during the COVID-19 pandemic: An umbrella review of meta-analyses","volume":"107","author":"Sahebi","year":"2021","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B30","doi-asserted-by":"publisher","first-page":"108586","DOI":"10.1016\/j.neuropharm.2021.108586","article-title":"Current controversies in medical cannabis: Recent developments in human clinical applications and potential therapeutics","volume":"191","author":"Schlag","year":"2021","journal-title":"Neuropharmacology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1007\/s40429-020-00326-8","article-title":"Therapeutic efficacy of cannabidiol (CBD): A review of the evidence from clinical trials and human laboratory studies","volume":"7","author":"Sholler","year":"2020","journal-title":"Curr. Addict. Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.bbr.2010.05.004","article-title":"Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors.","volume":"213","author":"Soares","year":"2010","journal-title":"Behav. Brain Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"881617","DOI":"10.3389\/fphar.2022.881617","article-title":"Case report: Cannabidiol-induced skin rash: A case series and key recommendations","volume":"13","author":"Souza","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"127","DOI":"10.31887\/DCNS.2017.19.2\/dstein","article-title":"Epidemiology of anxiety disorders: From surveys to nosology and back","volume":"19","author":"Stein","year":"2017","journal-title":"Dialogues Clin. Neurosci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jhealeco.2015.03.007","article-title":"The effect of medical marijuana laws on adolescent and adult use of marijuana, alcohol, and other substances","volume":"42","author":"Wen","year":"2015","journal-title":"J. Health Econ."},{"key":"B35","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1177\/026988119300700112","article-title":"Effects of ipsapirone and cannabidiol on human experimental anxiety","volume":"7","author":"Zuardi","year":"1993","journal-title":"J. Psychopharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"259","DOI":"10.3389\/fphar.2017.00259","article-title":"Inverted U-shaped dose-response curve of the anxiolytic effect of cannabidiol during public speaking in real life.","volume":"8","author":"Zuardi","year":"2017","journal-title":"Front. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.856846\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,3]],"date-time":"2022-10-03T01:30:47Z","timestamp":1664760647000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.856846\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,3]]},"references-count":37,"alternative-id":["10.3389\/fphar.2022.856846"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.856846","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,3]]},"article-number":"856846"}}