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      Mitragyna speciosa: Clinical, Toxicological Aspects and Analysis in Biological and Non-Biological Samples

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          Abstract

          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.

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          Most cited references109

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          Patterns of Kratom use and health impact in the US-Results from an online survey.

          Kratom preparations have raised concerns of public health and safety in the US. Investigation into the demographics, perceived beneficial and detrimental effects of Kratom as well as common doses and purposes of its use are important to properly evaluate its potential health impact.
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            Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users.

            Kratom (Mitragyna speciosa) preparations have been traditionally used in Southeast Asia for its medicinal properties. Lately, Kratom use has spread to Europe and the US, where abuse potential and health hazards increasingly emerge. This study is the first to measure systematically Kratom dependence, withdrawal symptoms, and drug craving in regular Kratom users in Malaysia.
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              Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa.

              The leaves of a tropical plant, Mitragyna speciosa KORTH (Rubiaceae), have been traditionally used as a substitute for opium. Phytochemical studies of the constituents of the plant growing in Thailand and Malaysia have led to the isolation of several 9-methoxy-Corynanthe-type monoterpenoid indole alkaloids, including new natural products. The structures of the new compounds were elucidated by spectroscopic and/or synthetic methods. The potent opioid agonistic activities of mitragynine, the major constituent of this plant, and its analogues were found in in vitro and in vivo experiments and the mechanisms underlying the analgesic activity were clarified. The essential structural features of mitragynines, which differ from those of morphine and are responsible for the analgesic activity, were elucidated by pharmacological evaluation of the natural and synthetic derivatives. Among the mitragynine derivatives, 7-hydroxymitragynine, a minor constituent of M. speciosa, was found to exhibit potent antinociceptive activity in mice.
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                Author and article information

                Journal
                Medicines (Basel)
                Medicines (Basel)
                medicines
                Medicines
                MDPI
                2305-6320
                04 March 2019
                March 2019
                : 6
                : 1
                : 35
                Affiliations
                [1 ]Centro de Investigação em Ciências da Saúde, Faculdade de Ciências da Saúde da Universidade da Beira Interior (CICS-UBI), 6200-506 Covilhã, Portugal; vaniaandbia@ 123456hotmail.com (V.M.); tiagorosadofful@ 123456hotmail.com (T.R.); sofia_soares_26@ 123456hotmail.com (S.S.); janitagoncalves@ 123456hotmail.com (J.G.); afluis27@ 123456gmail.com (Â.L.); deboracaramela50@ 123456gmail.com (D.C.); anaaysa95@ 123456gmail.com (A.Y.S.); apduarte@ 123456fcsaude.ubi.pt (A.P.D.)
                [2 ]Serviço de Química e Toxicologia Forenses, Instituto de Medicina Legal e Ciências Forenses—Delegação do Sul, 1169-201 Lisboa, Portugal; mario.j.barroso@ 123456inmlcf.mj.pt
                [3 ]Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Toxicología y Química Legal, Laboratorio de Asesoramiento Toxicológico Analítico (CENATOXA). Junín 956 7mo piso. Ciudad Autónoma de Buenos Aires (CABA), Buenos Aires C1113AAD, Argentina; nfernandez@ 123456ffyb.uba.ar
                Author notes
                [* ]Correspondence: egallardo@ 123456fcsaude.ubi.pt ; Tel.: +35-127-532-9002
                Author information
                https://orcid.org/0000-0003-0712-6522
                https://orcid.org/0000-0003-3333-5977
                https://orcid.org/0000-0002-1802-8998
                Article
                medicines-06-00035
                10.3390/medicines6010035
                6473843
                30836609
                62716d82-91f8-4814-8780-524b9274dcb1
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 January 2019
                : 27 February 2019
                Categories
                Review

                mitragyna speciosa,kratom,secondary metabolites,therapeutic uses,toxicology,analysis

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