RESEARCH MONOGRAPH · KDC-MN-155

Mitragynine (Kratom)

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

61/100

A complicated alkaloid with partial mu-opioid agonism, real abuse liability concerns, and pharmacology worth understanding

Mitragynine is the major alkaloid in Mitragyna speciosa leaves (kratom). The pharmacology has gotten substantial research attention in the last decade, mostly because the public health context made it impossible to ignore. The receptor profile is partial mu-opioid agonism with substantially lower efficacy than morphine at MOR, plus alpha-2 adrenergic agonism, plus serotonergic activity at 5-HT2A and 5-HT2C, plus some adenosine and other minor activities. So its not a clean mu-opioid agonist, but the mu activity is the part driving most of the discussion around abuse and dependence.

The Susruta Majumdar lab at Memorial Sloan Kettering and others have done structure-activity work showing that mitragynine itself is a partial agonist with G-protein-biased signaling at MOR, which is the basis for the (now somewhat-controversial) claim that kratom has less respiratory depression risk than full mu-opioid agonists. The biased agonism story has been complicated by later work suggesting the signaling profile is more nuanced than the original biased ligand hypothesis claimed.

The bigger pharmacological issue is metabolism. Mitragynine is converted to 7-hydroxymitragynine by hepatic CYP3A4, and 7-hydroxy is a substantially more potent and more efficacious mu-opioid agonist than the parent alkaloid. So the active species in vivo is a mixture, and the metabolic conversion rate varies between people, between strains of the plant, and depending on chronic versus acute exposure.

What we like: as a research tool for studying partial mu-opioid agonism and biased signaling, mitragynine is genuinely interesting. The receptor pharmacology has been increasingly well-characterized. The natural product chemistry is well-established.

What we dont like: the popular use as an unregulated supplement has produced real public health concerns. Dependence syndromes are documented and meaningful, withdrawal patterns resemble milder opioid withdrawal, and adulterated commercial products are common.

Mechanism: partially mapped. MOR partial agonism, alpha-2 adrenergic agonism, serotonergic effects. Active metabolite contribution is important.

Sourcing: legitimate research-grade isolated mitragynine is available from a small number of academic and specialty suppliers. The consumer kratom market is wildly variable and frequently adulterated.

Worth studying. The pharmacology is genuinely complicated and worth understanding rather than dismissing.

Evidence: 60
Mechanism: 70
Reliability: 65
Safety: 50
Sourcing: 55
Value: 55
Signal: 70
Staying power: 60

Plain-language summary Intrigue 70 / 100

Mitragynine is the principal alkaloid of kratom (Mitragyna speciosa), a Southeast Asian tree. It is a partial mu-opioid receptor agonist; at low doses it has stimulant effects, at higher doses opioid-like effects. Controversial regulatory status in the US. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Indole alkaloid / partial mu-opioid agonist

The principal alkaloid of Mitragyna speciosa (kratom), a partial mu-opioid agonist with low respiratory depression liability and significant abuse and dependence potential.

Abstract

Mitragynine (CAS 4098-40-2; molecular formula C23H30N2O4; molecular weight 398.49) is the principal indole alkaloid of Mitragyna speciosa (kratom), a tree native to Southeast Asia. The compound and its 7-hydroxymetabolite are partial mu-opioid receptor agonists with G-protein-biased signaling that produces analgesia with reduced respiratory depression compared with classical opioids at equivalent analgesic potency. Kratom and mitragynine have substantial dependence and addiction liability with chronic use; FDA has issued multiple warnings, and DEA has attempted scheduling (currently not federally scheduled but prohibited in some states). The compound is sold as kratom leaf, kratom extracts, and isolated mitragynine. Reported research dose ranges in the literature for kratom leaf are highly variable and span roughly 1 to 5 grams.

Mechanism of action

Partial mu-opioid receptor agonist with G-protein-biased signaling. Active metabolite 7-hydroxymitragynine is more potent.

Reported research dose ranges

Reported research dose ranges in the literature for kratom leaf span roughly 1 to 5 grams; isolated mitragynine amounts reported are lower.

References

Kruegel AC, et al. The medicinal chemistry and neuropharmacology of kratom. Neuropharmacology 2018.

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KDC-MN-155

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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Mitragynine (Kratom)

Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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