Kratom (Mitragyna speciosa)

Mechanism of action

Primary alkaloid mitragynine is a partial agonist at mu-opioid receptors with biased signaling — produces analgesia and mood elevation with less respiratory depression than classical opioids. 7-hydroxymitragynine, a minor alkaloid, is a more potent full agonist. Lower doses produce stimulant effects; higher doses produce sedation. Significant dependence and tolerance develop with regular use.

History

Kratom has been used by Southeast Asian populations for centuries as a stimulant and pain reliever. Modern Western use accelerated in the 2010s as an unscheduled alternative to opioids. The FDA has issued multiple warnings; several state and local jurisdictions have banned it. The DEA proposed scheduling it as Schedule I in 2016 but withdrew the proposal under pressure. Dependence is well-documented; deaths involving kratom have occurred.

Benefits

• Pain relief

  EVIDENCEC

  Anecdotal + small trials.

• Mood elevation

  EVIDENCEC

  User reports.

Side effects

• Dependence with regular usecommonsevere
• Withdrawal symptomscommonsevere
• Liver toxicity (case reports)raresevere

Cited research

• Kratom alkaloid pharmacology (Kruegel)2016
  PMID 27993006 ↗
• Kratom dependence and withdrawal (Vicknasingam)2010
  PMID 20598211 ↗
• Kratom use and harm in US: review (Henningfield)2018
  PMID 29486236 ↗

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