{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:19:41Z","timestamp":1792685981952,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Kratom is increasingly used in the United States for energy and self\u2010management of pain and mood. While its active alkaloid, mitragynine, has partial \u03bc\u2010opioid receptor agonist activity, clinical data on its abuse potential remain limited. This study evaluated abuse\u2010related outcomes following single and multiple doses of dried kratom leaf powder in healthy kratom\u2010naive adults in a randomized, double\u2010blind, placebo\u2010controlled study. Healthy participants (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009116) received a single oral dose or 15 consecutive daily doses of Mitra\u2010Leaf kratom capsules (4 cohorts: 500\u20134000\u2009mg dried leaf powder; equivalent to 6.65\u201353.2\u2009mg mitragynine;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912\u201313 per cohort,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200949 total) or placebo (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200967). Subjective effects were assessed using the Drug Effects Questionnaire (DEQ). Opioid withdrawal symptoms were evaluated using the Subjective Opioid Withdrawal Scale (SOWS) and Clinical Opiate Withdrawal Scale (COWS). Abuse\u2010related treatment\u2010emergent adverse events (ARTEAEs) were recorded. DEQ responses were dose\u2010related, except between the middle two dose levels with statistically significant increases in maximum effect and area\u2010under\u2010the\u2010curve compared to placebo observed only at the highest single dose. DEQ responses decreased following repeated dosing. No participants met the threshold for clinically meaningful opioid withdrawal based on COWS or SOWS. ARTEAEs occurred more frequently at higher doses but were generally mild and resolved without sequelae. No serious adverse events or deaths were reported. Oral administration of kratom at tested doses was well tolerated and associated with modest, dose\u2010related subjective effects, minimal withdrawal symptoms, and low ARTEAE rates. Findings support further research on kratom's safety and therapeutic potential, while emphasizing the importance of dose control and product standardization.\n                  <\/jats:p>","DOI":"10.1002\/dta.70089","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:02:38Z","timestamp":1779084158000},"page":"922-932","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Assessment of Abuse Potential\u2010Related Effects of Oral Dried Kratom Leaf Powder in Healthy Normal Participants Following Single and Multiple Daily Doses"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8831-8649","authenticated-orcid":false,"given":"Marion","family":"Coe","sequence":"first","affiliation":[{"name":"Pinney Associates Inc.  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Huestis","sequence":"additional","affiliation":[{"name":"Institute of Emerging Health Professions Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Wang","sequence":"additional","affiliation":[{"name":"Pinney Associates Inc.  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hudzik","sequence":"additional","affiliation":[{"name":"ALA BioPharma Consulting  Monroe New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bothmer","sequence":"additional","affiliation":[{"name":"JB PharmaConsult  Heerlen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Henningfield","sequence":"additional","affiliation":[{"name":"Pinney Associates Inc.  Bethesda Maryland USA"},{"name":"Johns Hopkins University School of Medicine Department of Psychiatry and Behavioral Sciences  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/10826080701205869"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2019.05.005"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2017.03.007"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-8741(88)90121-3"},{"key":"e_1_2_10_6_1","unstructured":"U.S. Food and Drug Administration. \u201cFDA and Kratom.\u201d (2024):https:\/\/www.fda.gov\/news\u2010events\/public\u2010health\u2010focus\/fda\u2010and\u2010kratom. Accessed 29 April 2025."},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2020.34.s1.05233"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b00360"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.9b00141"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.775073"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01208-y"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2024.2305798"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01273"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00128.2024"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76119-w"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-1795-5876"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants12040949"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.16366"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2024.114913"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-022-00736-8"},{"key":"e_1_2_10_21_1","article-title":"Mitragynine and 7\u2010Hydroxymitragynine: Bidirectional Effects on Breathing in Rats","author":"Zuarth Gonzalez J. D.","year":"2025","journal-title":"bioRxiv: The Preprint Server for Biology"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-022-06244-z"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12639"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-018-4974-9"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/00952990.2022.2083967"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.53401"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2025.2474249"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.32473\/edis\u2010ep653\u20102025"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2017.03.020"},{"key":"e_1_2_10_30_1","unstructured":"B. P.Giroir\u201c2018 Letter From the Assistant Secretary of Health to the Administrator of the Drug Enforcement Administration to Rescind Previous Support to Permanently Place Mitragynine and 7\u2010Hydroxymitragynine in Schedule I of the Controlled Substances Act \u201d2018https:\/\/images.go02.informamarkets.com\/Web\/Informa02\/%7b548e6d56\u20102ea4\u20104da4\u20109404\u20100348b56e9a88%7d_dhillon\u20108.16.2018\u2010response\u2010letter\u2010from\u2010ash\u2010radm\u2010giroir.pdf."},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-021-05934-4"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0000000000000435"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2018.1562133"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2020.107849"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2024.111329"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2015.1096434"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.15173"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2017.10.012"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1089\/caff.2019.0020"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1368980024000399"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-58496-8"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dadr.2023.100142"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29050984"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000001427"},{"key":"e_1_2_10_45_1","unstructured":"S.Galati \u201cIdentifying Relevant Adverse Events of Interest and Recommendation for Analysis and Presentation of Data in the NDA Submission \u201d [Presented at Cross\u2010Company Abuse Liability Council (CCALC) Meeting] September 27 2023; Rockville MD."},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajad.12862"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2008.05.007"}],"container-title":["Drug Testing and Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dta.70089","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/dta.70089","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dta.70089","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:37:22Z","timestamp":1783013842000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/dta.70089"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,17]]},"references-count":46,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/dta.70089"],"URL":"https:\/\/doi.org\/10.1002\/dta.70089","archive":["Portico"],"relation":{},"ISSN":["1942-7603","1942-7611"],"issn-type":[{"value":"1942-7603","type":"print"},{"value":"1942-7611","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,17]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}