Behavioral and neurochemical characterization of kratom (Mitragyna speciosa) extract

Psychopharmacology (Berl). 2014 Jan;231(1):13-25. doi: 10.1007/s00213-013-3201-y. Epub 2013 Jul 12.


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.

MeSH terms

  • Administration, Oral
  • Animals
  • Anxiety / psychology
  • Behavior, Animal / drug effects*
  • Blotting, Western
  • Drug Interactions
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • HEK293 Cells
  • Hot Temperature
  • Humans
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Mice
  • Mice, Knockout
  • Mitragyna / chemistry*
  • Naltrexone / analogs & derivatives
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Pain Threshold / drug effects
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, kappa / metabolism
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism


  • Narcotic Antagonists
  • Plant Extracts
  • Receptors, Dopamine D1
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • norbinaltorphimine
  • Naltrexone