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Behavioral and neurochemical characterization of kratom (Mitragyna speciosa) extract

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Abstract

Objective

Mitragyna speciosa and its extracts are named kratom (dried leaves, extract). It contains several alkaloids and is used in traditional medicine to alleviate musculoskeletal pain, hypertension, coughing, diarrhea, and as an opiate substitute for addicts. Abuse and addiction to kratom is described, and kratom has attracted increasing interest in Western countries. Individual effects of kratom on opioidergic, adrenergic, serotonergic, and dopaminergic receptors are known, but not all of the effects have been explained. Pharmacokinetic and pharmacodynamic data are needed.

Methods

The effects of kratom extract on mice behavior were investigated following oral (po), intraperitoneal (ip), and intracerebroventricular (icv) application. Receptor-binding studies were performed.

Results

In μ opioid receptor knockout mice (−/−) and wild type (+/+) animals, the extract reduced locomotor activity after ip and low po doses in +/+ animals, but not after icv administration. The ip effect was counteracted by 0.3 mg/kg of apomorphine sc, suggesting dopaminergic presynaptic activity. An analgesic effect was only found in −/− mice after icv application. Norbinaltorphimine abolished the analgesic effect, but not the inhibitory effect, on locomotor activity, indicating that the analgesic effect is mediated via κ opioid receptors. Oral doses, which did not diminish locomotor activity, impaired the acquisition of shuttle box avoidance learning. There was no effect on consolidation. Binding studies showed affinity of kratom to μ, δ, and κ opioid receptors and to dopamine D1 receptors.

Conclusions

The results obtained in drug-naïve mice demonstrate weak behavioral effects mediated via μ and κ opioid receptors.

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Acknowledgments

We gratefully acknowledge the expert assistance of Ms. M. Böx, Ms. P. Dehmel, Ms. D. Heidemann, Ms. G. Borkhardt and Ms. C. Knape.

Conflict of interest

None.

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Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, Medical Faculty, O. v. Guericke University, Leipziger Str. 44, 30124, Magdeburg, Germany

    Anne-Christin Stolt, Helmut Schröder, Gisela Grecksch, Volker Höllt & Axel Becker

  2. Center of Pharmacology and Toxicology, Georg August University, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Hartmud Neurath

  3. Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, D-66421, Homburg (Saar), Germany

    Markus R. Meyer & Hans H. Maurer

  4. Department of Psychiatry and Psychotherapy, Georg August University, von Siebold-Str. 5, 37075, Göttingen, Germany

    Nancy Ziebolz & Ursula Havemann-Reinecke

  5. DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain, 37075, Göttingen, Germany

    Ursula Havemann-Reinecke

Authors
  1. Anne-Christin Stolt
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  2. Helmut Schröder
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  3. Hartmud Neurath
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  4. Gisela Grecksch
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  5. Volker Höllt
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  6. Markus R. Meyer
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  7. Hans H. Maurer
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  8. Nancy Ziebolz
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  9. Ursula Havemann-Reinecke
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  10. Axel Becker
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Corresponding author

Correspondence to Axel Becker.

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Stolt, AC., Schröder, H., Neurath, H. et al. Behavioral and neurochemical characterization of kratom (Mitragyna speciosa) extract. Psychopharmacology 231, 13–25 (2014). https://doi.org/10.1007/s00213-013-3201-y

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  • DOI: https://doi.org/10.1007/s00213-013-3201-y

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