Mitragyna speciosa: Opioid Addiction Treatment and Risk of Use

Azka Muhammad Rusydan, Endang Lukitaningsih, Nanang Fakhrudin

Abstract

Kratom (Mitragyna speciosa (Korth.) Havil.) is a plant that originated from the rainforest in Southeast Asia, mainly grows in Thailand, Malaysia, and Indonesia. Kratom has been used traditionally as an herbal remedy for the treatment of various illnesses. Kratom gained notoriety due to its potential as an analgesic, opiate withdrawal treatment, anxiolytic, antidepressant, and antidiabetic with an unclear risk of addiction and toxicity fueled by a false sense of security due to its identity as a member of the coffee family. This article is a narrative review on kratom to highlight its pharmacological and toxicological properties, and the analytical method of Kratom, especially its potential as an opioid withdrawal therapy and its risk of abuse.

Keywords

kratom; kratom addiction; kratom toxicity; Mitragyna speciosa; mitragynine; 7-hydroxymitragynine

Full Text:

PDF

References

Aggarwal, G., Robertson, E., McKinlay, J., and Walter, E. (2018). Death from Kratom toxicity and the possible role of intralipid. Journal of the Intensive Care Society, 19(1), 61–63.

Ahmad, K., and Aziz, Z. (2012). Mitragyna speciosa use in the northern states of Malaysia: A cross-sectional study. Journal of Ethnopharmacology, 141(1), 446–450.

Alsarraf, E., Myers, J., Culbreth, S., and Fanikos, J. (2019). Kratom from Head to Toe—Case Reviews of Adverse Events and Toxicities. Current Emergency and Hospital Medicine Reports, 7(4), 141–168. https://doi.org/10.1007/s40138-019-00194-1

Andilala. (2019), November 5. BNN: Kratom dilarang total mulai 2022. Antara News. https://www.antaranews.com/berita/1147832/bnn-kratom-dilarang-total-mulai-2022

Antony, A., and Lee, T.-P. (2019). Herb-Induced Liver Injury With Cholestasis and Renal Injury Secondary to Short-Term Use of Kratom (Mitragyna speciosa). American Journal of Therapeutics, 26(4), e546. https://doi.org/10.1097/MJT.0000000000000802

Apryani, E., Taufik Hidayat, M., Moklas, M. A. A., Fakurazi, S., and Farah Idayu, N. (2010). Effects of mitragynine from Mitragyna speciosa Korth leaves on working memory. Journal of Ethnopharmacology, 129(3), 357–360.

Arndt, T., Claussen, U., Güssregen, B., Schröfel, S., Stürzer, B., Werle, A., and Wolf, G. (2011). Kratom alkaloids and O-desmethyltramadol in urine of a “Krypton” herbal mixture consumer. Forensic Science International, 208(1), 47–52.

Assanangkornchai, S., Muekthong, A., Sam-angsri, N., and Pattanasattayawong, U. (2007). The Use of Mitragynine speciosa (“Krathom”), an Addictive Plant, in Thailand. Substance Use & Misuse, 42(14), 2145–2157. https://doi.org/10.1080/10826080701205869

Azizi, J., Ismail, S., Mordi, M. N., Ramanathan, S., Said, M. I. M., and Mansor, S. M. (2010). In Vitro and in Vivo Effects of Three Different Mitragyna speciosa Korth Leaf Extracts on Phase II Drug Metabolizing Enzymes—Glutathione Transferases (GSTs). Molecules, 15(1), 432–441. https://doi.org/10.3390/molecules15010432

Badan Pengawas Obat dan Makanan. (2016). Surat Edaran Nomor Hk. 04.4.42.421.09.16.1740 Tahun 2016 Tentang Pelarangan Penggunaan Mitragyna speciosa (Kratom) Dalam Obat Tradisional Dan Suplemen Kesehatan, No. Hk. 04.4.42.421.09.16.1740 Tahun 2016. https://www.pom.go.id/new/view/more/berita/12112/Pelarangan-Penggunaan-Mitragyna-Speciosa--Kratom--dalam-Obat-Tradisional-dan-Suplemen-Kesehatan.html

Blanco, M. (1845). Flora de Filipinas: segun el sistema sexual de Linneo. Michigan : Sto. Thomas, por Candido Lopez.

Brown, P. N., Lund, J. A., and Murch, S. J. (2017). A botanical, phytochemical and ethnomedicinal review of the genus Mitragyna korth: Implications for products sold as kratom. Journal of Ethnopharmacology, 202, 302–325.

Buresh, M. (2018). Treatment of Kratom Dependence With Buprenorphine-Naloxone Maintenance. Journal of Addiction Medicine, 12(6), 481–483.

Casey, C., Conley, T., Heise, A., Thomas, T., and Ayres, P. (2015). Quantitative and qualitative analysis of mitragynine in Kratom (Mitragyna speciosa) by GC–MS, LC-MS/MS and UPLC-PDA. Journal of Regulatory Science, 3(1).

Castillo, A., Payne, J. D., and Nugent, K. (2017). Posterior Reversible Leukoencephalopathy Syndrome After Kratom Ingestion. Baylor University Medical Center Proceedings, 30(3), 355–357. https://doi.org/10.1080/08998280.2017.11929647

Chan, K. B., Pakiam, C., and Rahim, R. A. (2005). Psychoactive plant abuse: The identification of mitragynine in ketum and in ketum preparations. Bulletin on Narcotics, 8.

Chittrakarn, S., Keawpradub, N., Sawangjaroen, K., Kansenalak, S., and Janchawee, B. (2010). The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of kratom leaves (Mitragyna speciosa Korth.). Journal of Ethnopharmacology, 129(3), 344–349. https://doi.org/10.1016/j.jep.2010.03.035

Chittrakarn, S., Penjamras, P., and Keawpradub, N. (2012). Quantitative analysis of mitragynine, codeine, caffeine, chlorpheniramine and phenylephrine in a kratom (Mitragyna speciosa Korth.) cocktail using high-performance liquid chromatography. Forensic Science International, 217(1–3), 81–86.

Chittrakarn, S., Sawangjaroen, K., Prasettho, S., Janchawee, B., and Keawpradub, N. (2008). Inhibitory effects of kratom leaf extract (Mitragyna speciosa Korth.) on the rat gastrointestinal tract. Journal of Ethnopharmacology, 116(1), 173–178. https://doi.org/10.1016/j.jep.2007.11.032

Chua, L. S. L., and Schmelzer, G. H. (2001). Mitragyna speciosa (Korth.) Havil. Medicinal and Poisonous Plants. 2, 380–382.

Cinosi, E., Martinotti, G., Simonato, P., Singh, D., Demetrovics, Z., Roman-Urrestarazu, A., Bersani, F. S., Vicknasingam, B., Piazzon, G., Li, J.-H., Yu, W.-J., Kapitány-Fövény, M., Farkas, J., Di Giannantonio, M., and Corazza, O. (2015). Following “the Roots” 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 [Research Article]. BioMed Research International. https://doi.org/10.1155/2015/968786

Corkery, J. M., Streete, P., Claridge, H., Goodair, C., Papanti, D., Orsolini, L., Schifano, F., Sikka, K., Körber, S., and Hendricks, A. (2019). Characteristics of deaths associated with kratom use. Journal of Psychopharmacology, 33(9), 1102–1123.

Davidson, L., Rawat, M., Stojanovski, S., and Chandrasekharan, P. (2019). Natural drugs, not so natural effects: Neonatal abstinence syndrome secondary to ‘kratom.’ Journal of Neonatal-Perinatal Medicine, 12(1), 109–112. https://doi.org/10.3233/NPM-1863

Departement Of Health. 2017. Misuse of Drugs (Designation) Order 2017, No. S.I. No. 174 Of 2017. Dublin: The Stationery Office.

Dorman, C., Wong, M., and Khan, A. (2015). Cholestatic hepatitis from prolonged kratom use: A case report. Hepatology, 61(3), 1086–1087. https://doi.org/10.1002/hep.27612

Eldridge, W. B., Foster, C., and Wyble, L. (2018). Neonatal Abstinence Syndrome Due to Maternal Kratom Use. Pediatrics, 142(6). https://doi.org/10.1542/peds.2018-1839

EMCDDA. (2012). Kratom (Mitragyna speciosa) drug profile. Kratom Drug Profile. https://www.emcdda.europa.eu/publications/drug-profiles/kratom_en

Idayu, N. F., Hidayat, M. T., Moklas, M. A. M., Sharida, F., Raudzah, A. R. N, Shamima, A. R., and Apryani, E. (2011). Antidepressant-like effect of mitragynine isolated from Mitragyna speciosa Korth in mice model of depression. Phytomedicine, 18(5), 402–407. https://doi.org/10.1016/j.phymed.2010.08.011

Food and Drug Administration. (2018), Februari 21. FDA oversees destruction and recall of kratom products; and reiterates its concerns on risks associated with this opioid. FDA. https://www.fda.gov/news-events/press-announcements/fda-oversees-destruction-and-recall-kratom-products-and-reiterates-its-concerns-risks-associated

Fowble, K. L., and Musah, R. A. (2019). A validated method for the quantification of mitragynine in sixteen commercially available Kratom (Mitragyna speciosa) products. Forensic Science International, 299, 195–202.

Fu, H., Cid, F., Dworkin, N., Cocores, J., and Shore, G. (2015). Screening and Identification of Mitragynine and 7-Hydroxymitragynine in Human Urine by LC-MS/MS. Chromatography, 2(2), 253–264. https://doi.org/10.3390/chromatography2020253

Great Britain. (2016). Psychoactive Substances Act 2016, no. 2016 c. 2. London: The Stationary Office. http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted

Hanapi, N. A., Ismail, S., and Mansor, S. M. (2013). Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities. Pharmacognosy Research, 5(4), 241–246. https://doi.org/10.4103/0974-8490.118806

Harun, N., Hassan, Z., Navaratnam, V., Mansor, S. M., and Shoaib, M. (2015). Discriminative stimulus properties of mitragynine (kratom) in rats. Psychopharmacology, 232(13), 2227–2238. https://doi.org/10.1007/s00213-015-3866-5

Hassan, Z., Muzaimi, M., Navaratnam, V., Yusoff, N. H. M., Suhaimi, F. W., Vadivelu, R., Vicknasingam, B. K., Amato, D., von Hörsten, S., Ismail, N. I. W., Jayabalan, N., Hazim, A. I., Mansor, S. M., and Müller, C. P. (2013). From Kratom to mitragynine and its derivatives: Physiological and behavioural effects related to use, abuse, and addiction. Neuroscience & Biobehavioral Reviews, 37(2), 138–151.

Haviland, M. D. (1897). NOTES ON THE GREY PLOVER ON THE YENESEI. Ibis, 102.

Hazim, A. I., Ramanathan, S., Parthasarathy, S., Muzaimi, M., and Mansor, S. M. (2014). Anxiolytic-like effects of mitragynine in the open-field and elevated plus-maze tests in rats. The Journal of Physiological Sciences, 64(3), 161–169. https://doi.org/10.1007/s12576-014-0304-0

Hemby, S. E., McIntosh, S., Leon, F., Cutler, S. J., and McCurdy, C. R. (2019). Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids mitragynine and 7-hydroxymitragynine. Addiction Biology, 24(5), 874–885.

Jessica, E. A., Edward, W. B., and Christopher, R. M. (2011, Mei 1). Mitragyna speciosa, A Psychoactive Tree from Southeast Asia with Opioid Activity. Current Topics in Medicinal Chemistry. https://www.eurekaselect.com/87838/article

Kapp, F. G., Maurer, H. H., Auwärter, V., Winkelmann, M., and Hermanns-Clausen, M. (2011). Intrahepatic Cholestasis Following Abuse of Powdered Kratom (Mitragyna speciosa). Journal of Medical Toxicology, 7(3), 227–231. https://doi.org/10.1007/s13181-011-0155-5

Kikura-Hanajiri, R., Kawamura, M., Maruyama, T., Kitajima, M., Takayama, H., and Goda, Y. (2009). Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant “kratom” (Mitragyna speciosa) by LC-ESI-MS. Forensic Toxicology, 27(2), 67–74. https://doi.org/10.1007/s11419-009-0070-5

Kong, W. M., Chik, Z., Ramachandra, M., Subramaniam, U., Aziddin, R. E. R., and Mohamed, Z. (2011). Evaluation of the Effects of Mitragyna speciosa Alkaloid Extract on Cytochrome P450 Enzymes Using a High Throughput Assay. Molecules, 16(9), 7344–7356. https://doi.org/10.3390/molecules16097344

Kowalczuk, A. P., Łozak, A., and Zjawiony, J. K. (2013). Comprehensive methodology for identification of Kratom in police laboratories. Forensic Science International, 233(1–3), 238–243. https://doi.org/10.1016/j.forsciint.2013.09.016

Kumarnsit, E., Vongvatcharanon, U., Keawpradub, N., and Intasaro, P. (2007). Fos-like immunoreactivity in rat dorsal raphe nuclei induced by alkaloid extract of Mitragyna speciosa. Neuroscience Letters, 416(2), 128–132.

Le, D., Goggin, M. M., and Janis, G. C. (2012). Analysis of Mitragynine and Metabolites in Human Urine for Detecting the Use of the Psychoactive Plant Kratom. Journal of Analytical Toxicology, 36(9), 616–625. https://doi.org/10.1093/jat/bks073

Lee, M. J., Ramanathan, S., Mansor, S. M., and Tan, S. C. (2020). Development of an ELISA for detection of mitragynine and its metabolites in human urine. Analytical Biochemistry, 599, 113733. https://doi.org/10.1016/j.ab.2020.113733

León, F., Habib, E., Adkins, J. E., Furr, E. B., McCurdy, C. R., and Cutler, S. J. (2009). Phytochemical Characterization of the Leaves of Mitragyna speciosa Grown in USA. Natural Product Communication, 4(7), 907–910.

Lesiak, A. D., Cody, R. B., Dane, A. J., and Musah, R. A. (2014). Rapid detection by direct analysis in real time-mass spectrometry (DART-MS) of psychoactive plant drugs of abuse: The case of Mitragyna speciosa aka “Kratom.” Forensic Science International, 242, 210–218. https://doi.org/10.1016/j.forsciint.2014.07.005

Lu, S., Tran, B. N., Nelsen, J. L., and Aldous, K. M. (2009). Quantitative analysis of mitragynine in human urine by high performance liquid chromatography-tandem mass spectrometry. Journal of Chromatography B, 877(24), 2499–2505. https://doi.org/10.1016/j.jchromb.2009.06.024

Mackay, L., and Abrahams, R. (2018). Novel case of maternal and neonatal kratom dependence and withdrawal. Canadian Family Physician, 64, 121–122.

Macko, E., Weisbach, J. A., and Douglas, B. (1972). Some observations on the pharmacology of mitragynine. Archives Internationales De Pharmacodynamie Et De Therapie, 198(1), 145–161.

Matsumoto, K., Horie, S., Ishikawa, H., Takayama, H., Aimi, N., Ponglux, D., and Watanabe, K. (2004). Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa. Life Sciences, 74(17), 2143–2155. https://doi.org/10.1016/j.lfs.2003.09.054

McWhirter, L., and Morris, S. (2010). A Case Report of Inpatient Detoxification after Kratom (Mitragyna speciosa) Dependence. European Addiction Research, 16(4), 229–231. https://doi.org/10.1159/000320288

Meier, U., Mercer‐Chalmers‐Bender, K., Scheurer, E., and Dussy, F. (2020). Development, validation, and application of an LC–MS/MS method for mitragynine and 7-hydroxymitragynine analysis in hair. Drug Testing and Analysis, 12(2), 280–284. https://doi.org/10.1002/dta.2746

Menteri Pertanian Republik Indonesia. (2020). Keputusan Menteri Pertanian Republik Indonesia Nomor 104/KPTS/HK.140/M/2/2020. Jakarta: Kementerian Pertanian Republik Indonesia.

Miquel, F. A. W. (1856). Flora van Nederlandsch Indië (Vol. 2, No. 2). Bavarian: van der Post.

Mousa, M. S., Sephien, A., Gutierrez, J., and O’Leary, C. (2018). N-Acetylcysteine for Acute Hepatitis Induced by Kratom Herbal Tea. American Journal of Therapeutics, 25(5), e550–e551. https://doi.org/10.1097/MJT.0000000000000631

Mudge, E., and Brown, P. (2016). Determination of Mitragynine in Mitragyna speciosa Raw Materials and Finished Products by Liquid Chromatography with UV Detection: Single-Laboratory Validation. Journal of AOAC International, 100. https://doi.org/10.5740/jaoacint.16-0220

Nelsen, J. L., Lapoint, J., Hodgman, M. J., and Aldous, K. M. (2010). Seizure and Coma Following Kratom (Mitragynina speciosa Korth) Exposure. Journal of Medical Toxicology, 6(4), 424–426. https://doi.org/10.1007/s13181-010-0079-5

Neng, N. R., Ahmad, S. M., Gaspar, H., and Nogueira, J. M. F. (2015). Determination of mitragynine in urine matrices by bar adsorptive microextraction and HPLC analysis. Talanta, 144, 105–109. https://doi.org/10.1016/j.talanta.2015.05.038

Nilus, R. (2011). Rehabilitation of Tropical Rainforest Ecosystems. 14.

Oberbarnscheidt, T., and Miller, N. (2019). Kratom- A Lethal Drug on the Rise. J Addiction Prevention, 77(1), 6.

Olsen, E. O. (2019). Notes from the Field: Unintentional Drug Overdose Deaths with Kratom Detected — 27 States, July 2016–December 2017. MMWR. Morbidity and Mortality Weekly Report, 68. https://doi.org/10.15585/mmwr.mm6814a2

Osborne, C. S., Overstreet, A. N., Rockey, D. C., and Schreiner, A. D. (2019). Drug-Induced Liver Injury Caused by Kratom Use as an Alternative Pain Treatment Amid an Ongoing Opioid Epidemic. Journal of Investigative Medicine High Impact Case Reports, 7, 2324709619826167. https://doi.org/10.1177/2324709619826167

Papsun, D. M., Chan-Hosokawa, A., Friederich, L., Brower, J., Graf, K., and Logan, B. (2019). The Trouble With Kratom: Analytical and Interpretative Issues Involving Mitragynine. Journal of Analytical Toxicology, 43(8), 615–629. https://doi.org/10.1093/jat/bkz064

Parthasarathy, S., Ramanathan, S., Ismail, S., Adenan, M. I., Mansor, S. M., and Murugaiyah, V. (2010). Determination of mitragynine in plasma with solid-phase extraction and rapid HPLC–UV analysis, and its application to a pharmacokinetic study in rat. Analytical and Bioanalytical Chemistry, 397(5), 2023–2030. https://doi.org/10.1007/s00216-010-3707-7

Pathak, V., Hahn, C., Cabellon, M., and Aris, R. (2014). Adult Respiratory Distress Syndrome Secondary To The Use Of Herbal Drug Kratom. American Journal of Respiratory and Critical Care Medicine, 189(1), 1.

Phongprueksapattana, S., Putalun, W., Keawpradub, N., and Wungsintaweekul, J. (2008). Mitragyna speciosa: Hairy Root Culture for Triterpenoid Production and High Yield of Mitragynine by Regenerated Plants. Zeitschrift Für Naturforschung C, 63(9–10), 691–698. https://doi.org/10.1515/znc-2008-9-1014

Prozialeck, W. C., Jivan, J. K., and Andurkar, S. V. (2012). Pharmacology of Kratom: An Emerging Botanical Agent With Stimulant, Analgesic and Opioid-Like Effects. J Am Osteopath Assoc, 112(12), 792–799.

Purintrapiban, J., Keawpradub, N., Kansenalak, S., Chittrakarn, S., Janchawee, B., and Sawangjaroen, K. (2011). Study on glucose transport in muscle cells by extracts from Mitragyna speciosa (Korth) and mitragynine. Natural Product Research, 25(15), 1379–1387. https://doi.org/10.1080/14786410802267627

Raffa, R. B. (2014). Kratom and Other Mitragynines. CRC Press.

Raini, M. (2017). Kratom (Mitragyna speciosa Korth): Manfaat, Efek Samping dan Legalitas. Media Penelitian dan Pengembangan Kesehatan, 27(3), 175–184. https://doi.org/10.22435/mpk.v27i3.6806.175-184

Ramanathan, S., Parthasarathy, S., Murugaiyah, V., Magosso, E., Tan, S. C., and Mansor, S. M. (2015). Understanding the physicochemical properties of mitragynine, a principal alkaloid of Mitragyna speciosa, for preclinical evaluation. Molecules (Basel, Switzerland), 20(3), 4915–4927. https://doi.org/10.3390/molecules20034915

Ramli, M. D. B. C., Chong, W. N., Chong, B. M. R., Uzid, M. B. M., and Sanusi, J. (2019). The neurotoxicity assessment in addicted adult zebrafish (DANIO RERIO) induced by Mitragyna speciosa. International Journal of Medical Toxicology & Legal Medicine, 22(3and4), 63. https://doi.org/10.5958/0974-4614.2019.00060.3

Ratsch, C. (2005). The Encyclopedia of Psychoactive Plants (J. R. Baker, Penerj.). Park Street Press.

Razafimandimbison, S. G., and Bremer, B. (2001). Tribal Delimitation of Naucleeae (Cinchonoideae, Rubiaceae): Inference from Molecular and Morphological Data. Systematics and Geography of Plants, 71(2), 515–538. https://doi.org/10.2307/3668697

Rech, M. A., Donahey, E., Cappiello Dziedzic, J. M., Oh, L., and Greenhalgh, E. (2015). New drugs of abuse. Pharmacotherapy, 35(2), 189–197. https://doi.org/10.1002/phar.1522

Rokib, M. (2019, Maret 22). Kepala BBPOM Beri Penjelasan Terkait Larangan Jual Kratom Dalam Bentuk Olahan—Tribun Pontianak. https://pontianak.tribunnews.com/2019/03/22/kepala-bbpom-beri-penjelasan-terkait-larangan-jual-kratom-dalam-bentuk-olahan

Sattaburuth, C., and Wannapiroon, P. (2021). Sensorization of Things Intelligent Technology for Sport Science to Develop an Athlete's Physical Potential. Higher Education Studies, 11(2), 201-214.

Schmuhl, K. K., Gardner, S. M., Cottrill, C. B., and Bonny, A. E. (2020). Home induction and outpatient treatment of kratom use disorder with buprenorphine-naloxone: A case report in a young adult. Substance Abuse, 41(3), 311–314. https://doi.org/10.1080/08897077.2019.1671945

Singh, D., Grundmann, O., Murugaiyah, V., Rahim, A. B. M., Chawarski, M., and Balasingam, V. (2019a). Improved sexual functioning of long-term daily users of Mitragyna speciosa (Korth.). Journal of Herbal Medicine, 100293.

Singh, D., Müller, C. P., and Vicknasingam, B. K. (2014). Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug and Alcohol Dependence, 139, 132–137. https://doi.org/10.1016/j.drugalcdep.2014.03.017

Singh, D., Narayanan, S., Müller, C. P., Swogger, M. T., Chear, N. J. Y., Dzulkapli, E. B., Yusoff, N. S. M., Ramachandram, D. S., León, F., McCurdy, C. R., and Vicknasingam, B. (2019b). Motives for using Kratom (Mitragyna speciosa Korth.) among regular users in Malaysia. Journal of Ethnopharmacology, 233, 34–40.

Suwanlert, S. (1975). A Study of Kratom Eaters in Thailand. Buletin on Narcotics, 27(3), 21–27.

Steudel, E. G. (1841). Nomenclator botanicus: seu: Synonymia plantarum universalis, enumerans ordine alphabetico nomina atque synonyma, tum generica tum specifica, et a Linnaeo et a recentioribus de re botanica scriptoribus plantis phanerogamis imposita (Vol. 2). New York: Typis et sumptibus JG Cottae.

Takayama, H. (2004). Chemistry and Pharmacology of Analgesic Indole Alkaloids from the Rubiaceous Plant, Mitragyna speciosa. Chemical and Pharmaceutical Bulletin, 52(8), 916–928. https://doi.org/10.1248/cpb.52.916

Takayama, H., Ishikawa, H., Kurihara, M., Kitajima, M., Aimi, N., Ponglux, D., Koyama, F., Matsumoto, K., Moriyama, T., Yamamoto, L. T., Watanabe, K., Murayama, T., and Horie, S. (2002). Studies on the Synthesis and Opioid Agonistic Activities of Mitragynine-Related Indole Alkaloids: Discovery of Opioid Agonists Structurally Different from Other Opioid Ligands. Journal of Medicinal Chemistry, 45(9), 1949–1956. https://doi.org/10.1021/jm010576e

Tanguay, P. (2011). Kratom in Thailand (SSRN Scholarly Paper ID 1908849). Social Science Research Network. https://papers.ssrn.com/abstract=1908849

Tayabali, K., Bolzon, C., Foster, P., Patel, J., and Kalim, M. O. (2018). Kratom: A dangerous player in the opioid crisis. Journal of Community Hospital Internal Medicine Perspectives, 8(3), 107–110. https://doi.org/10.1080/20009666.2018.1468693

Tohda, M., Thongpraditchote, S., Matsumoto, K., Murakami, Y., Sakai, S., Aimi, N., Takayama, H., Tongroach, P., and Watanabe, H. (1997). Effects of Mitragynine on cAMP Formation Mediated by .DELTA.-Opiate Receptors in NG108-15 Cells. Biological & Pharmaceutical Bulletin, 20(4), 338–340. https://doi.org/10.1248/bpb.20.338

Váradi, A., Marrone, G. F., Palmer, T. C., Narayan, A., Szabó, M. R., Le Rouzic, V., Grinnell, S. G., Subrath, J. J., Warner, E., Kalra, S., Hunkele, A., Pagirsky, J., Eans, S. O., Medina, J. M., Xu, J., Pan, Y.-X., Borics, A., Pasternak, G. W., McLaughlin, J. P., and Majumdar, S. (2016). Mitragynine/Corynantheidine Pseudoindoxyls as Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit Β-Arrestin-2. Journal of Medicinal Chemistry, 59(18), 8381–8397.

Veltri, C., and Grundmann, O. (2019). Current perspectives on the impact of Kratom use. Substance Abuse and Rehabilitation, 10, 23–31. https://doi.org/10.2147/SAR.S164261

Vicknasingam, B., Narayanan, S., Beng, G. T., and Mansor, S. M. (2010). The informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy. The International Journal on Drug Policy, 21(4), 283–288. https://doi.org/10.1016/j.drugpo.2009.12.003

Wang, M., Carrell, E. J., Ali, Z., Avula, B., Avonto, C., Parcher, J. F., and Khan, I. A. (2014). Comparison of three chromatographic techniques for the detection of mitragynine and other indole and oxindole alkaloids in Mitragyna speciosa (kratom) plants. Journal of Separation Science, 37(12), 1411–1418. https://doi.org/10.1002/jssc.201301389

Wikramanayake, E. D., Dinerstein, E., and Loucks, C. J. (2002). Terrestrial Ecoregions of the Indo-Pacific: A Conservation Assessment. Island Press.

Ya, K., Tangamornsuksan, W., Scholfield, C. N., Methaneethorn, J., and Lohitnavy, M. (2019). Pharmacokinetics of mitragynine, a major analgesic alkaloid in kratom (Mitragyna speciosa): A systematic review. Asian Journal of Psychiatry, 43, 73–82. https://doi.org/10.1016/j.ajp.2019.05.016

Yusof, A. (2019), September 21. Penang farmers want to cash in on ‘miracle drug’ kratom as Putrajaya mulls blanket ban. CNA. https://www.channelnewsasia.com/news/asia/malaysia-kratom-drugs-opioid-illegal-ban-11910832

Zarembo, J. E., Douglas, B., Valenta, J., and Weisbach, J. A. (1974). Metabolites of Mitragynine. Journal of Pharmaceutical Sciences, 63(9), 1407–1415. https://doi.org/10.1002/jps.2600630916

Zhou, J., and Zhou, S. (2010). Antihypertensive and neuroprotective activities of rhynchophylline: The role of rhynchophylline in neurotransmission and ion channel activity. Journal of Ethnopharmacology, 132(1), 15–27. https://doi.org/10.1016/j.jep.2010.08.041

DOI: https://doi.org/10.20961/jpscr.v7i2.50942

Refbacks

  • There are currently no refbacks.