{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T15:50:59Z","timestamp":1776959459373,"version":"3.51.4"},"reference-count":122,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalisation in Axis I","award":["Project POCI-01-0145-FEDER-007491"],"award-info":[{"award-number":["Project POCI-01-0145-FEDER-007491"]}]},{"name":"Program Santander-Totta Universidades","award":["Bolsa BID\/UBI-Santander Universidades\/2018"],"award-info":[{"award-number":["Bolsa BID\/UBI-Santander Universidades\/2018"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["Project UID\/Multi \/00709\/2013"],"award-info":[{"award-number":["Project UID\/Multi \/00709\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["Scientific Employment: scientific area of Microbiology"],"award-info":[{"award-number":["Scientific Employment: scientific area of Microbiology"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicines"],"abstract":"<jats:p>The abuse of psychotropic substances is a well-known phenomenon, and many of them are usually associated with ancestral traditions and home remedies. This is the case of Mitragyna speciosa (kratom), a tropical tree used to improve work performance and to withstand great heat. According to several published studies, the main reasons for kratom consumption involve improving sexual performance and endurance, but also social and recreational uses for the feeling of happiness and euphoria; it is also used for medical purposes as a pain reliever, and in the treatment of diarrhea, fever, diabetes, and hypertension. However, this plant has gained more popularity amongst young people over the last years. Since it is available on the internet for purchase, its use is now widely as a drug of abuse, namely as a new psychoactive substance, being a cheaper alternative to opioids that does not require medical prescription in most countries. According to internet surveys by the European Monitoring Centre for Drugs and Drug Addiction in 2008 and 2011, kratom was one of the most widely supplied new psychoactive substances. The composition of kratom is complex; in fact, more than 40 different alkaloids have been identified in Mitragyna speciosa so far, the major constituent being mitragynine, which is exclusive to this plant. Besides mitragynine, alkaloids such as corynantheidine and 7-hydroxamitragynine also present pharmacological effects, a feature that may be attributed to the remaining constituents as well. The main goal of this review is not only to understand the origin, chemistry, consumption, and analytical methodologies for analysis and mechanism of action, but also the use of secondary metabolites of kratom as therapeutic drugs and the assessment of potential risks associated with its consumption, in order to aid health professionals, toxicologists, and police authorities in cases where this plant is present.<\/jats:p>","DOI":"10.3390\/medicines6010035","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T05:22:26Z","timestamp":1551676946000},"page":"35","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Mitragyna speciosa: Clinical, Toxicological Aspects and Analysis in Biological and Non-Biological Samples"],"prefix":"10.3390","volume":"6","author":[{"given":"V\u00e2nia","family":"Meireles","sequence":"first","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Tiago","family":"Rosado","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8848-2734","authenticated-orcid":false,"given":"M\u00e1rio","family":"Barroso","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Qu\u00edmica e Toxicologia Forenses, Instituto de Medicina Legal e Ci\u00eancias Forenses\u2014Delega\u00e7\u00e3o do Sul, 1169-201 Lisboa, Portugal"}]},{"given":"Sofia","family":"Soares","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Joana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0712-6522","authenticated-orcid":false,"given":"\u00c2ngelo","family":"Lu\u00eds","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"given":"D\u00e9bora","family":"Caramelo","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Ana Y.","family":"Sim\u00e3o","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Nicol\u00e1s","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Universidad de Buenos Aires, Facultad de Farmacia y Bioqu\u00edmica, C\u00e1tedra de Toxicolog\u00eda y Qu\u00edmica Legal, Laboratorio de Asesoramiento Toxicol\u00f3gico Anal\u00edtico (CENATOXA). Jun\u00edn 956 7mo piso. Ciudad Aut\u00f3noma de Buenos Aires (CABA), Buenos Aires C1113AAD, Argentina"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3333-5977","authenticated-orcid":false,"given":"Ana Paula","family":"Duarte","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-8998","authenticated-orcid":false,"given":"Eugenia","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Ci\u00eancias da Sa\u00fade, Faculdade de Ci\u00eancias da Sa\u00fade da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,4]]},"reference":[{"key":"ref_1","first-page":"1634","article-title":"Evaluation of Herbal Dietary Supplements Marketed on the Internet for Recreational Use","volume":"39","author":"Dennehy","year":"2014","journal-title":"Complement. Altern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.drugalcdep.2014.03.017","article-title":"Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users","volume":"139","author":"Singh","year":"2014","journal-title":"Drug Alcohol Depend."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/02791072.2015.1012610","article-title":"Social Functioning of Kratom (Mitragyna speciosa) Users in Malaysia","volume":"47","author":"Singh","year":"2015","journal-title":"J. Psychoact. Drugs"},{"key":"ref_4","unstructured":"European Monitoring Centre for Drugs and Drug Adiction (2019, January 12). New Psychoactive Substances in Europe. Available online: http:\/\/www.emcdda.europa.eu\/system\/files\/publications\/65\/TD0415135ENN.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.2174\/156802611795371305","article-title":"Mitragyna speciosa, A Psychoactive Tree from Southeast Asia with Opioid Activity","volume":"11","author":"Adkins","year":"2011","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1248\/cpb.52.916","article-title":"Chemistry and Pharmacology of Analgesic Indole Alkaloids from the Rubiaceous Plant, Mitragyna speciosa","volume":"52","author":"Takayama","year":"2004","journal-title":"Chem. Pharm. Bull."},{"key":"ref_7","first-page":"263","article-title":"Genus Mitragyna: Ethnomedicinal uses and pharmacological studies","volume":"3","author":"Gong","year":"2012","journal-title":"Phytopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.cll.2012.06.002","article-title":"Drug abuse: Newly-Emerging drugs and trends","volume":"32","author":"Davis","year":"2012","journal-title":"Clin. Lab. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s11418-009-0325-9","article-title":"The botanical origin of kratom (Mitragyna speciosa; Rubiaceae) available as abused drugs in the Japanese markets","volume":"63","author":"Maruyama","year":"2009","journal-title":"J. Nat. Med."},{"key":"ref_10","first-page":"1","article-title":"Kratom in Thailand","volume":"13","author":"Tanguay","year":"2011","journal-title":"Transl. Inst. Legis. Reform Drug Policies"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.drugpo.2012.09.004","article-title":"Pattern and consequences of krathom (Mitragyna speciosa Korth.) use among male villagers in southern Thailand: A qualitative study","volume":"24","author":"Saingam","year":"2018","journal-title":"Int. J. Drug Policy"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.brainresbull.2016.05.004","article-title":"Traditional and non-traditional uses of Mitragynine (Kratom): A survey of the literature","volume":"126","author":"Singh","year":"2016","journal-title":"Brain Res. Bull."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.drugpo.2009.12.003","article-title":"The informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy","volume":"21","author":"Vicknasingam","year":"2010","journal-title":"Int. J. Drug Policy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1080\/02791072.2015.1096434","article-title":"Experiences of Kratom Users: A Qualitative Analysis","volume":"47","author":"Swogger","year":"2015","journal-title":"J. Psychoact. Drugs"},{"key":"ref_15","first-page":"2145","article-title":"The Use of Mitragynine speciosa (\u201cKrathom\u201d), an Addictive Plant, in Thailand","volume":"6084","author":"Assanangkornchai","year":"2006","journal-title":"Subst. Use Misuse"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.drugalcdep.2017.03.007","article-title":"Patterns of Kratom use and health impact in the US\u2014Results from an online survey","volume":"176","author":"Grundmann","year":"2017","journal-title":"Drug Alcohol Depend."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.forsciint.2010.06.030","article-title":"\u201cLegal highs\u201d on the net-Evaluation of UK-based Websites, products and product information","volume":"206","author":"Schmidt","year":"2011","journal-title":"Forensic Sci. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"330","DOI":"10.3109\/10826080903443628","article-title":"Legal Highs on the Internet","volume":"45","author":"Hillebrand","year":"2010","journal-title":"Subst. Use Misuse"},{"key":"ref_19","unstructured":"European Monitoring Centre for Drugs and Drug Adiction (2019, January 11). Khat Drug Profile. Available online: http:\/\/www.emcdda.europa.eu\/publications\/drug-profiles\/khat."},{"key":"ref_20","unstructured":"United Nations Office on Drugs and Crime (UNODC) (2019, January 16). UNODC Early Warning Advisory (EWA) on New Psychoactive Substances (NPS). Available online: https:\/\/www.unodc.org\/LSS\/Home\/NPS."},{"key":"ref_21","unstructured":"(2019, January 11). Kratom (Mitragyna speciosa) Drug Profile. Available online: http:\/\/www.emcdda.europa.eu\/publications\/drug-profiles\/kratom."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.jep.2012.03.009","article-title":"Mitragyna speciosa use in the northern states of Malaysia: A cross-sectional study","volume":"141","author":"Ahmad","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0378-8741(88)90121-3","article-title":"Ethnopharmacology of kratom and mitragyna alkaloids","volume":"23","author":"Jansen","year":"1988","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0378-8741(89)90053-6","article-title":"Ethnopharmacology of kratom and the Mitragyna alkaloids","volume":"25","author":"Shellard","year":"1989","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.jfda.2017.04.001","article-title":"New psychoactive substances of natural origin: A brief review","volume":"25","author":"Feng","year":"2017","journal-title":"J. Food Drug Anal."},{"key":"ref_26","unstructured":"Raffa, R.B. (2014). Kratom and Other Mitragynines: The Chemistry and Pharmacology of Opioids from a Non-Opium Source, CRC Press. [1st ed.]."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.forsciint.2010.10.025","article-title":"Kratom alkaloids and O-desmethyltramadol in urine of a \u201cKrypton\u201d herbal mixture consumer","volume":"208","author":"Schro","year":"2011","journal-title":"Forensic Sci. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1055\/s-2006-959578","article-title":"A New Indole Alkaloid, 7a-Hydroxy-7H-mitragynine, from Mitragyna speciosa in Thailand","volume":"60","author":"Ponglux","year":"1994","journal-title":"Planta Med."},{"key":"ref_29","first-page":"792","article-title":"Pharmacology of Kratom: An Emerging Botanical Agent with Stimulant, Analgesic and Opioid-Like Effects","volume":"112","author":"Prozialeck","year":"2012","journal-title":"J. Am. Osteopath. Assoc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/S0040-4039(01)90746-4","article-title":"Mitragyna alkaloids: The structure of stipulatine","volume":"4","author":"Hendrickson","year":"1963","journal-title":"Tetrahedron Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.dib.2018.04.001","article-title":"Metabolomics data of Mitragyna speciosa leaf using LC-ESI-TOF-MS","volume":"18","author":"Veeramohan","year":"2018","journal-title":"Data Br."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.forsciint.2014.07.005","article-title":"Rapid detection by direct analysis in real time-mass spectrometry (DART-MS) of psychoactive plant drugs of abuse: The case of Mitragyna speciosa aka \u201cKratom\u201d","volume":"242","author":"Lesiak","year":"2014","journal-title":"Forensic Sci. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1007\/s00216-010-3707-7","article-title":"Determination of mitragynine in plasma with solid-phase extraction and rapid HPLC-UV analysis, and its application to a pharmacokinetic study in rat","volume":"397","author":"Parthasarathy","year":"2010","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.3390\/molecules20034915","article-title":"Understanding the physicochemical properties of mitragynine, a principal alkaloid of Mitragyna speciosa, for preclinical evaluation","volume":"20","author":"Ramanathan","year":"2015","journal-title":"Molecules"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1055\/s-0034-1382760","article-title":"Evaluation of in vitro absorption, distribution, metabolism, and excretion (ADME) properties of mitragynine, 7-hydroxymitragynine, and mitraphylline","volume":"80","author":"Manda","year":"2014","journal-title":"Planta Med."},{"key":"ref_36","first-page":"2421","article-title":"Pharmacokinetics of mitragynine in man","volume":"9","author":"Trakulsrichai","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1111\/j.1360-0443.2008.02209.x","article-title":"Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa Korth)","volume":"103","author":"Boyer","year":"2013","journal-title":"Addiction"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Avery, B.A., Boddu, S.P., Sharma, A., Furr, E.B., Leon, F., Cutler, S.J., and McCurdy, C.R. (2018). Comparative Pharmacokinetics of Mitragynine after Oral Administration of Mitragyna speciosa (Kratom) Leaf Extracts in Rats. Planta Med., in press.","DOI":"10.1055\/a-0770-3683"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yusof, S.R., Mohd Uzid, M., Teh, E.-H., Hanapi, N.A., Mohideen, M., Mohamad Arshad, A.S., Mordi, M.N., Loryan, I., and Hammarlund-Udenaes, M. (2018). Rate and extent of mitragynine and 7-hydroxymitragynine blood\u2013brain barrier transport and their intra-brain distribution: The missing link in pharmacodynamic studies. Addict. Biol., in press.","DOI":"10.1111\/adb.12661"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1515\/dmdi-2012-0039","article-title":"Mitragyna speciosa Korth leaves extracts induced the CYP450 catalyzed aminopyrine-N-demethylase (APND) and UDP-glucuronosyl transferase (UGT) activities in male Sprague-Dawley rat livers","volume":"28","author":"Azizi","year":"2013","journal-title":"Drug Metab. Drug Interact."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7344","DOI":"10.3390\/molecules16097344","article-title":"Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay","volume":"16","author":"Kong","year":"2011","journal-title":"Molecules"},{"key":"ref_42","first-page":"1","article-title":"Metabolite profiling and identification of enzymes responsible for the metabolism of mitragynine, the major alkaloid of Mitragyna speciosa (kratom)","volume":"14","author":"Kamble","year":"2018","journal-title":"Xenobiotica"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1021\/acs.chemrestox.8b00257","article-title":"Cytochrome P450 1A1, 2C9, 2C19, and 3A4 Polymorphisms Account for Interindividual Variability of Toxicological Drug Metabolism in Cynomolgus Macaques","volume":"31","author":"Uno","year":"2018","journal-title":"Chem. Res. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1007\/s00216-011-4660-9","article-title":"Metabolism studies of the Kratom alkaloid speciociliatine, a diastereomer of the main alkaloid mitragynine, in rat and human urine using liquid chromatography-linear ion trap mass spectrometry","volume":"399","author":"Philipp","year":"2011","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/jat\/bku137","article-title":"Mitragynine \u2018Kratom\u2019 Related Fatality: A Case Report with Postmortem Concentrations","volume":"39","author":"Mcintyre","year":"2014","journal-title":"J. Anal. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"241","DOI":"10.4103\/0974-8490.118806","article-title":"Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities","volume":"5","author":"Hanapi","year":"2013","journal-title":"Pharmacogn. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/968786","article-title":"Following \u201cthe Roots\u201d of Kratom (Mitragyna speciosa): The Evolution of an Enhancer from a Traditional Use to Increase Work and Productivity in Southeast Asia to a Recreational Psychoactive Drug in Western Countries","volume":"2015","author":"Cinosi","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_48","first-page":"812","article-title":"In vitro evaluation of cytochrome P450 induction and the inhibition potential of mitragynine, a stimulant alkaloid","volume":"27","author":"Koe","year":"2012","journal-title":"Toxicol. In Vitr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/fsn3.789","article-title":"Potential inhibition of major human cytochrome P450 isoenzymes by selected tropical medicinal herbs\u2014Implication for herb\u2013drug interactions","volume":"7","author":"Showande","year":"2019","journal-title":"Food Sci. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3109\/19390211.2013.793541","article-title":"An evidence-based systematic review of kratom (Mitragyna speciosa) by the natural standard research collaboration","volume":"10","author":"Ulbricht","year":"2013","journal-title":"J. Diet. Suppl."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s12024-018-0049-9","article-title":"Fatal combination of mitragynine and quetiapine\u2014A case report with discussion of a potential herb-drug interaction","volume":"15","author":"Hughes","year":"2018","journal-title":"Forensic Sci. Med. Pathol."},{"key":"ref_52","first-page":"249","article-title":"Psychoactive plant abuse: The identification of mitragynine in ketum and in ketum preparations","volume":"249","author":"Chan","year":"2007","journal-title":"Bull. Narc."},{"key":"ref_53","first-page":"598","article-title":"Kratom: A Case of a Legal High","volume":"46","author":"Roche","year":"2008","journal-title":"Clin. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"999","DOI":"10.2165\/11596830-000000000-00000","article-title":"Herbal Medicines for the Management of Opioid Addiction","volume":"25","author":"Ward","year":"2011","journal-title":"CNS Drugs"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.lfs.2004.10.086","article-title":"Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa","volume":"78","author":"Matsumoto","year":"2005","journal-title":"Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.neubiorev.2012.11.012","article-title":"From Kratom to mitragynine and its derivatives: Physiological and behavioural effects related to use, abuse, and addiction","volume":"37","author":"Hassan","year":"2013","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/S0024-3205(98)00075-7","article-title":"Identification of opioid receptor subtypes in antinociceptive actions of supraspinally-administered mitragynine in mice","volume":"62","author":"Thongpradichote","year":"1998","journal-title":"Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0306-3623(98)00265-1","article-title":"Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa","volume":"33","author":"Yamamoto","year":"1999","journal-title":"Gen. Pharmacol."},{"key":"ref_59","first-page":"261","article-title":"Pharmacologic and clinical assessment of kratom","volume":"75","author":"White","year":"2018","journal-title":"Bull. Am. Soc. Hosp. Pharm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00213-013-3201-y","article-title":"Behavioral and neurochemical characterization of kratom (Mitragyna speciosa) extract","volume":"231","author":"Stolt","year":"2014","journal-title":"Psychopharmacology"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Hemby, S.E., McIntosh, S., Leon, F., Cutler, S.J., and McCurdy, C.R. (2018). Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids mitragynine and 7-hydroxymitragynine. Addict. Biol., in press.","DOI":"10.1111\/adb.12639"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1213\/XAA.0000000000000857","article-title":"Kratom and General Anesthesia: A Case Report and Review of the Literature","volume":"12","author":"Vermaire","year":"2019","journal-title":"A A Pract."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"464","DOI":"10.3389\/fphar.2016.00464","article-title":"Mitragyna speciosa leaf extract exhibits antipsychotic-like effect with the potential to alleviate positive and negative symptoms of psychosis in mice","volume":"7","author":"Vijeepallam","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0024-3205(97)00023-4","article-title":"Inhibitory effect of mitragynine, an alkaloid with analgesic effect from Thai medicinal plant Mitragyna speciosa, on electrically stimulated contraction of isolated guinea-pig ileum through the opioid receptor","volume":"60","author":"Watanabe","year":"1997","journal-title":"Life Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S0924-9338(11)71761-8","article-title":"P01-50-Kratom and alcohol dependence: Clinical symptoms, withdrawal treatment and pharmacological mechanisms\u2014A case report","volume":"26","year":"2011","journal-title":"Eur. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.lfs.2005.04.042","article-title":"Inhibitory effect of mitragynine, an analgesic alkaloid from Thai herbal medicine, on neurogenic contraction of the vas deferens","volume":"78","author":"Matsumoto","year":"2005","journal-title":"Life Sci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Lu, J., Wei, H., Wu, J., Fadzly, M., and Jamil, A. (2014). Evaluation of the Cardiotoxicity of Mitragynine and Its Analogues Using Human Induced Pluripotent Stem Cell- Derived Cardiomyocytes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0115648"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1055\/s-2005-837822","article-title":"Indole alkaloids of a Thai medicinal herb, Mitragyna speciosa, that has opioid agonistic effect in guinea-pig ileum","volume":"71","author":"Horie","year":"2005","journal-title":"Planta Med."},{"key":"ref_69","first-page":"39","article-title":"Effects of the extracts from Mitragyna speciosa Korth. leaves on analgesic and behavioral activities in experimental animals","volume":"29","author":"Reanmongkol","year":"2017","journal-title":"Songklanakarin J. Sci. Technol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4103\/0974-8490.65514","article-title":"The evaluation of antinociceptive activity of alkaloid, methanolic, and aqueous extracts of Malaysian Mitragyna speciosa Korth leaves in rats","volume":"2","author":"Sabetghadam","year":"2010","journal-title":"Pharmacogn. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ejphar.2006.08.013","article-title":"Involvement of \u03bc-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragyna speciosa","volume":"549","author":"Matsumoto","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jep.2011.04.011","article-title":"Mitragynine inhibits the COX-2 mRNA expression and prostaglandin E2 production induced by lipopolysaccharide in RAW264.7 macrophage cells","volume":"136","author":"Utar","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1159\/000226292","article-title":"Anti-Inflammatory and Antinociceptive Effects of Mitragyna speciosa Korth","volume":"18","author":"Mossadeq","year":"2009","journal-title":"Med. Princ. Pract."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jep.2007.11.032","article-title":"Inhibitory effects of kratom leaf extract (Mitragyna speciosa Korth.) on the rat gastrointestinal tract","volume":"116","author":"Chittrakarn","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0014-2999(02)01588-1","article-title":"Effect of mitragynine, derived from Thai folk medicine, on gastric acid secretion through opioid receptor in anesthetized rats","volume":"443","author":"Tsuchiya","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.jep.2013.02.008","article-title":"Subchronic exposure to mitragynine, the principal alkaloid of Mitragyna speciosa, in rats","volume":"146","author":"Sabetghadam","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1080\/14786410802267627","article-title":"Study on glucose transport in muscle cells by extracts from Mitragyna speciosa (Korth) and mitragynine","volume":"25","author":"Purintrapiban","year":"2011","journal-title":"Nat. Prod. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.fitote.2006.11.012","article-title":"Effect of Mitragyna speciosa aqueous extract on ethanol withdrawal symptoms in mice","volume":"78","author":"Kumarnsit","year":"2007","journal-title":"Fitoterapia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.phymed.2010.08.011","article-title":"Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression","volume":"18","author":"Moklas","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1111\/adb.12385","article-title":"Chronic mitragynine (kratom) enhances punishment resistance in natural reward seeking and impairs place learning in mice","volume":"22","author":"Ismail","year":"2017","journal-title":"Addict. Biol."},{"key":"ref_81","first-page":"5810","article-title":"The effects on motor behaviour and short-term memory tasks in mice following an acute administration of Mitragyna speciosa alkaloid extract and mitragynine","volume":"5","author":"Hazim","year":"2011","journal-title":"J. Med. Plants"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1080\/02791072.2018.1555345","article-title":"Long-Term Cognitive Effects of Kratom (Mitragyna speciosa Korth.) Use","volume":"51","author":"Singh","year":"2018","journal-title":"J. Psychoact. Drugs"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.3390\/molecules14103964","article-title":"Evaluation of antioxidant and antibacterial activities of aqueous, methanolic and alkaloid extracts from Mitragyna speciosa (rubiaceae family) leaves","volume":"14","author":"Parthasarathy","year":"2009","journal-title":"Molecules"},{"key":"ref_84","first-page":"21","article-title":"A study of kratom eaters in Thailand","volume":"27","author":"Suwanlert","year":"1975","journal-title":"Bull. Narc."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/02791072.2018.1562133","article-title":"Kratom Withdrawal: A Systematic Review with Case Series","volume":"51","author":"Stanciu","year":"2019","journal-title":"J. Psychoact. Drugs"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1097\/AOG.0000000000002871","article-title":"Use of Kratom, an Opioid-like Traditional Herb, in Pregnancy","volume":"132","author":"Smid","year":"2018","journal-title":"Obstet. Gynecol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Davidson, L., Rawat, M., Stojanovski, S., and Chandrasekharan, P. (2018). Natural Drugs, Not So Natural Effects: Neonatal Abstinence Syndrome Secondary to \u2018Kratom\u2019. J. Neonatal-Perinat. Med., 1\u20134.","DOI":"10.3233\/NPM-1863"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.drugalcdep.2017.10.012","article-title":"Kratom use and mental health: A systematic review","volume":"183","author":"Swogger","year":"2018","journal-title":"Drug Alcohol Depend."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"432","DOI":"10.3390\/molecules15010432","article-title":"In vitro and in vivo effects of three different Mitragyna speciosa korth leaf extracts on phase II drug metabolizing enzymes-glutathione transferases (GSTs)","volume":"15","author":"Azizi","year":"2010","journal-title":"Molecules"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jep.2010.07.013","article-title":"Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in Rodent","volume":"131","author":"Harizal","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fnins.2015.00189","article-title":"Subchronic toxicity study of standardized methanolic extract of Mitragyna speciosa Korth in Sprague-Dawley Rats","volume":"9","author":"Ilmie","year":"2015","journal-title":"Front. Neurosci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.tox.2008.07.024","article-title":"Malaysian Kratom, a phyto-pharmaceutical of abuse: Studies on the mechanism of its cytotoxicity","volume":"253","author":"Saidin","year":"2008","journal-title":"Toxicology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3389\/fpsyt.2017.00062","article-title":"Biochemical benefits, diagnosis, and clinical risks evaluation of kratom","volume":"8","author":"Fluyau","year":"2017","journal-title":"Front. Psychiatry"},{"key":"ref_94","unstructured":"Rusli, N., Amanah, A., Kaur, G., Adenan, M.I., Sulaiman, S.F., Wahab, H.A., and Tan, M.L. (2019). The inhibitory effects of mitragynine on P-glycoprotein in vitro. Naunyn-Schmiedebergs Arch. Pharmacol., 1\u201316. Available online: https:\/\/link.springer.com\/article\/10.1007%2Fs00210-018-01605-y."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1007\/s13181-010-0079-5","article-title":"Seizure and Coma Following Kratom (Mitragynina speciosa Korth) Exposure","volume":"6","author":"Nelsen","year":"2010","journal-title":"J. Med. Toxicol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1093\/anatox\/35.4.242","article-title":"Unintentional Fatal Intoxications with Mitragynine and O-Desmethyltramadol from the Herbal Blend Krypton","volume":"35","author":"Kronstrand","year":"2011","journal-title":"J. Anal. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/ADM.0b013e318221fbfa","article-title":"A Coincidence of Addiction to \u201ckratom\u201d and Severe Primary Hypothyroidism","volume":"5","author":"Hypothyroidism","year":"2011","journal-title":"Am. Soc. Addict. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s13181-011-0155-5","article-title":"Hermanns-Clausen, M. Intrahepatic Cholestasis Following Abuse of Powdered Kratom (Mitragyna speciosa)","volume":"7","author":"Kapp","year":"2011","journal-title":"J. Med. Toxicol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1159\/000320288","article-title":"A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence","volume":"16","author":"McWhirter","year":"2010","journal-title":"Eur. Addict. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.forsciint.2016.12.020","article-title":"Mitragynine concentrations in two fatalities","volume":"271","author":"Domingo","year":"2017","journal-title":"Forensic Sci. Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e2582","DOI":"10.1002\/hup.2582","article-title":"Changing trends in the use of kratom (Mitragyna speciosa) in Southeast Asia","volume":"32","author":"Singh","year":"2017","journal-title":"Hum. Psychopharmacol. Clin. Exp."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jep.2018.12.038","article-title":"Motives for using Kratom (Mitragyna speciosa Korth.) among regular users in Malaysia","volume":"233","author":"Singh","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_103","unstructured":"(2019, January 18). Food and Drug Administration Statement from FDA Commissioner Scott Gottlieb, M.D., on the Agency\u2019s Scientific Evidence on the Presence of Opioid Compounds in Kratom, Underscoring Its Potential for Abuse, Available online: https:\/\/www.fda.gov\/newsevents\/newsroom\/pressannouncements\/ucm595622.htm."},{"key":"ref_104","unstructured":"Raffa, R.B. (2014). Detection of mitragyne and its analogs. Kratom and Other Mitragynines: The Chemistry and Pharmacology of Opioids from a Non-Opium Source, CRC Press."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1002\/jssc.201301389","article-title":"Comparison of three chromatographic techniques for the detection of mitragynine and other indole and oxindole alkaloids in Mitragyna speciosa (kratom) plants","volume":"37","author":"Wang","year":"2014","journal-title":"J. Sep. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.forsciint.2013.09.016","article-title":"Comprehensive methodology for identification of Kratom in police laboratories","volume":"233","author":"Kowalczuk","year":"2013","journal-title":"Forensic Sci. Int."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.forsciint.2013.01.014","article-title":"A simple HPLC-DAD method for the detection and quantification of psychotropic mitragynine in Mitragyna speciosa (ketum) and its products for the application in forensic investigation","volume":"226","author":"Parthasarathy","year":"2013","journal-title":"Forensic Sci. Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jpba.2016.11.055","article-title":"Evaluation of ion mobility spectrometry for the detection of mitragynine in kratom products","volume":"134","author":"Fuenffinger","year":"2017","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.forsciint.2014.08.011","article-title":"Development of indirect competitive ELISA for quantification of mitragynine in Kratom (Mitragyna speciosa (Roxb.) Korth.)","volume":"244","author":"Limsuwanchote","year":"2015","journal-title":"Forensic Sci. Int."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00216-010-4464-3","article-title":"Monitoring of kratom or Krypton intake in urine using GC-MS in clinical and forensic toxicology","volume":"400","author":"Philipp","year":"2011","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"18","DOI":"10.5740\/jaoacint.16-0220","article-title":"Determination of mitragynine in Mitragyna speciosa raw materials and finished products by liquid chromatography with UV detection: Single-laboratory validation","volume":"100","author":"Mudge","year":"2017","journal-title":"J. AOAC Int."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.ultsonch.2011.10.001","article-title":"UAE, MAE, SFE-CO2 and classical methods for the extraction of Mitragyna speciosa leaves","volume":"19","author":"Orio","year":"2012","journal-title":"Ultrason. Sonochem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1093\/jat\/bks073","article-title":"Analysis of Mitragynine and Metabolites in Human Urine for Detecting the Use of the Psychoactive Plant Kratom","volume":"36","author":"Le","year":"2012","journal-title":"J. Anal. Toxicol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1002\/jms.1607","article-title":"Studies on the metabolism of mitragynine, the main alkaloid of the herbal drug Kratom, in rat and human urine using liquid chromatography-linear ion trap mass spectrometry","volume":"44","author":"Philipp","year":"2009","journal-title":"J. Mass Spectrom."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1002\/dta.1970","article-title":"Mitragynine (Kratom)\u2014Monitoring in sports drug testing","volume":"8","author":"Guddat","year":"2016","journal-title":"Drug Test. Anal."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/anatox\/35.1.54","article-title":"A drug toxicity death involving propylhexedrine and mitragynine","volume":"35","author":"Holler","year":"2011","journal-title":"J. Anal. Toxicol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1016\/j.jchromb.2009.06.024","article-title":"Quantitative analysis of mitragynine in human urine by high performance liquid chromatography-tandem mass spectrometry","volume":"877","author":"Lu","year":"2009","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.4314\/tjpr.v16i7.28","article-title":"Solid phase extraction method for determination of mitragynine in urine and its application to mitragynine excretion study in rats receiving caffeine","volume":"16","author":"Prutipanlai","year":"2017","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.talanta.2015.05.038","article-title":"Determination of mitragynine in urine matrices by bar adsorptive microextraction and HPLC analysis","volume":"144","author":"Neng","year":"2015","journal-title":"Talanta"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jchromb.2018.02.010","article-title":"Identification of five Mitragyna alkaloids in urine using liquid chromatography-quadrupole\/time of flight mass spectrometry","volume":"1080","author":"Basiliere","year":"2018","journal-title":"J. Chromatogr. B"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/bmc.731","article-title":"A high-performance liquid chromatographic method for determination of mitragynine in serum and its application to a pharmacokinetic study in rats","volume":"183","author":"Janchawee","year":"2007","journal-title":"Biomed. Chromatogr."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.forsciint.2011.10.027","article-title":"Quantitative analysis of mitragynine, codeine, caffeine, chlorpheniramine and phenylephrine in a kratom (Mitragyna speciosa Korth.) cocktail using high-performance liquid chromatography","volume":"217","author":"Chittrakarn","year":"2012","journal-title":"Forensic Sci. Int."}],"container-title":["Medicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6320\/6\/1\/35\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:36:01Z","timestamp":1760186161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6320\/6\/1\/35"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,4]]},"references-count":122,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["medicines6010035"],"URL":"https:\/\/doi.org\/10.3390\/medicines6010035","relation":{},"ISSN":["2305-6320"],"issn-type":[{"value":"2305-6320","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,4]]}}}