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Kratom\u2010associated adverse drug reactions (ADRs) continue to be reported and raise concerns about the safety profile of kratom. However, studies are lacking that describe the overall pattern of kratom\u2010associated adverse events and quantify the association between kratom and adverse events. ADRs reported to the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021 were used to address these knowledge gaps. Descriptive analysis was conducted to analyze kratom\u2010related adverse reactions. Conservative pharmacovigilance signals based on observed\u2010to\u2010expected ratios with shrinkage were estimated by comparing kratom to all other natural products and drugs. Based on 489 deduplicated kratom\u2010related ADR reports, users were young (mean age 35.5\u2009years), and more often male (67.5%) than female patients (23.5%). Cases were predominantly reported since 2018 (94.2%). Fifty\u2010two disproportionate reporting signals in 17 system\u2010organ\u2010class categories were generated. The observed\/reported number of kratom\u2010related accidental death reports was 63\u2010fold greater than expected. There were eight strong signals related to addiction or drug withdrawal. An excess proportion of ADR reports were about kratom\u2010related drug complaints, toxicity to various agents, and seizures. Although further research is needed to assess the safety of kratom, clinicians and consumers should be aware that real\u2010world evidence points to potential safety threats.<\/jats:p>","DOI":"10.1111\/cts.13505","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T10:43:59Z","timestamp":1677753839000},"page":"1002-1011","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["An evaluation of adverse drug reactions and outcomes attributed to kratom in the <scp>US<\/scp> Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021"],"prefix":"10.1111","volume":"16","author":[{"given":"Xiaotong","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Ndungu","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-1617","authenticated-orcid":false,"given":"Sanya B.","family":"Taneja","sequence":"additional","affiliation":[{"name":"Intelligent Systems Program University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryann R.","family":"Chapin","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan B.","family":"Egbert","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishi","family":"Akenapalli","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3331-1839","authenticated-orcid":false,"given":"Mary F.","family":"Paine","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane Washington USA"},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences Washington State University  Spokane Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra L.","family":"Kane\u2010Gill","sequence":"additional","affiliation":[{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane Washington USA"},{"name":"Department of Biomedical Informatics University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2993-2085","authenticated-orcid":false,"given":"Richard D.","family":"Boyce","sequence":"additional","affiliation":[{"name":"School of Pharmacy University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Center of Excellence for Natural Product Drug Interaction Research  Spokane Washington USA"},{"name":"Department of Biomedical Informatics University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/968786"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76119-w"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14030620"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40122-020-00151-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2017.03.007"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.801855"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802611795371305"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.12788\/acp.0012"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ypmed.2019.105851"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2019.112462"},{"key":"e_1_2_9_12_1","unstructured":"Commissioner O of the. 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