Forensic Toxicology

, Volume 34, Issue 2, pp 213–226 | Cite as

Chemical characterization and in vitro cyto- and genotoxicity of ‘legal high’ products containing Kratom (Mitragyna speciosa)

  • Ana Sofia Oliveira
  • Sónia Fraga
  • Félix Carvalho
  • Ana Margarida Araújo
  • Cristiana Costa Pereira
  • João Paulo Teixeira
  • Maria de Lourdes Bastos
  • Paula Guedes de PinhoEmail author
Original Article


Kratom is a popular ‘legal high’ mainly constituted by alkaloids extracted from the Mitragyna speciosa plant with mitragynine (MG) as the dominant active substance. The increasing use of Kratom for recreational purposes has alerted risk assessment bodies of the lack of information on the real composition and its potential health risks. The present study aimed to determine and compare the MG composition of 13 commercial products of Kratom sold online and in “smartshops”, by gas chromatography–mass spectrometry. For the first time, the cytotoxicity induced by pure MG and Kratom, extracts was evaluated in in vitro models of human intestinal (Caco-2) and neuronal (SH-SY5Y) cells after 6 and 24 h. Genotoxicity was also evaluated in intestinal Caco-2 cells following 24 h of exposure to subtoxic concentrations using the comet assay. The obtained results revealed an inconsistency between the information (‘power’) provided in labels and the MG content. Cytotoxicity tests revealed a concentration-dependent decrease in cell viability in both cellular models, with the SH-SY5Y cells being more sensitive to the Kratom extracts. The resin and the ‘powered extracts’ were the most cytotoxic samples, with IC50 values significantly lower than the leaf extracts and pure MG (P < 0.0001 vs. leaf extracts and MG). In addition, significant DNA damage was observed in Caco-2 cells exposed to these extracts but not to pure MG, which suggests that other substances present in the extracts or interactions involving Kratom components might be responsible for the observed effects.


Kratom GC–MS Cytotoxicity Genotoxicity Caco-2 cell line SH-SY5Y cell line 



This work received financial support from the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project Pest-C/EQB/LA0006/2013.

Compliance with ethical standards

Conflict of interest

There are no financial or other relations that could lead to a conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

11419_2015_305_MOESM1_ESM.doc (51 kb)
Supplementary material 1 (DOC 51 kb)
11419_2015_305_MOESM2_ESM.doc (1.1 mb)
Supplementary material 2 (DOC 1152 kb)
11419_2015_305_MOESM3_ESM.doc (96 kb)
Supplementary material 3 (DOC 95 kb)


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Copyright information

© Japanese Association of Forensic Toxicology and Springer Japan 2016

Authors and Affiliations

  • Ana Sofia Oliveira
    • 1
  • Sónia Fraga
    • 1
  • Félix Carvalho
    • 1
  • Ana Margarida Araújo
    • 1
  • Cristiana Costa Pereira
    • 2
    • 3
  • João Paulo Teixeira
    • 2
    • 3
  • Maria de Lourdes Bastos
    • 1
  • Paula Guedes de Pinho
    • 1
    Email author
  1. 1.UCIBIO-REQUIMTE, Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de FarmáciaUniversidade do PortoPortoPortugal
  2. 2.Departamento de Saúde AmbientalInstituto Nacional de Saúde Doutor Ricardo JorgePortoPortugal
  3. 3.EPIUnit - Instituto de Saúde PúblicaUniversidade do PortoPortoPortugal

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