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Mitragynine

MIT · CAS 4098-40-2

Indole alkaloid

Formula

C₂₃H₃₀N₂O₄

Molecular Weight

398.5 g/mol

Abundance in Leaf

40–66%

Last Reviewed

2026-03-12

What Is Mitragynine?

Mitragynine is the most abundant alkaloid in kratom leaves, typically making up 40–66% of the total alkaloid content. It acts as a partial agonist at the mu-opioid receptor — meaning it activates pain-relief pathways but with a built-in ceiling effect, unlike full agonists such as morphine. At lower doses users commonly report increased energy and focus, while higher doses tend to produce sedation and pain relief. This dual nature is a key reason kratom behaves differently depending on the amount consumed. If you see "MIT" on a Certificate of Analysis, this is the compound being measured.

Dose-Dependent Effects

Low dose (1–5 g leaf equivalent)

Mild stimulation and increased alertness
Enhanced sociability and talkativeness
Reduced fatigue

As reported in Kruegel & Bhowmik 2016; Prozialeck et al. 2012, not a recommendation.

High dose (5–15 g leaf equivalent)

Analgesia (pain relief)
Sedation and relaxation
Euphoria in some users
Nausea and constipation at higher end

As reported in Kruegel & Bhowmik 2016; Singh et al. 2016, not a recommendation.

Receptor Activity

Receptor	Ki (nM)	Activity Type	What This Means
Mu-opioid (MOR)	160–700	Partial agonist (Emax 30–44%)	Activates the main pain-relief receptor but only partially — producing analgesia with a built-in ceiling that limits respiratory depression compared to full opioids.
Kappa-opioid (KOR)	—	Antagonist	Blocks the kappa receptor, which is associated with dysphoria and hallucinations. This may explain why kratom is less likely to cause unpleasant psychological effects seen with some opioids.
Delta-opioid (DOR)	—	Antagonist	Blocks the delta-opioid receptor. The functional significance in kratom's overall effect profile is still being studied.
Alpha-2A adrenoceptor	~1260	Complex activity	Interacts with the same receptor targeted by clonidine, a medication used for blood pressure and opioid withdrawal. May contribute to kratom's reported effects on withdrawal symptoms.
Serotonin (5-HT receptors)	—	Moderate affinity	Shows activity at several serotonin receptor subtypes, which may contribute to the mood-related effects reported by users.

Safety & Adverse Effects

Reported adverse effects

Nausea, constipation, dizziness, dry mouth, and itching are the most commonly reported side effects. Seizures have been reported in rare cases, typically involving high doses or polysubstance use.

Source: Swogger & Walsh 2018; Eastlack et al. 2020

Dependence potential

Regular use can lead to physical dependence and a withdrawal syndrome characterized by irritability, muscle aches, insomnia, and runny nose — generally described as milder than classical opioid withdrawal.

Source: Singh et al. 2014; Prozialeck et al. 2012

Hepatotoxicity context

Rare case reports of liver injury exist, but causality is difficult to establish due to frequent polysubstance use and adulterated products. Pure mitragynine has not shown direct hepatotoxicity in controlled animal studies at typical doses.

Source: Eastlack et al. 2020; Philipp et al. 2020

Contraindications

Should not be combined with CNS depressants (benzodiazepines, alcohol, opioids), MAOIs, or serotonergic drugs without medical supervision. Pre-existing liver conditions warrant caution.

Source: Henningfield et al. 2018

Drug Interactions

CYP3A4 inhibitors (ketoconazole, grapefruit juice)

major

Mitragynine is primarily metabolized by CYP3A4. Inhibitors can significantly increase plasma levels.

CYP2D6 substrates (codeine, tramadol, SSRIs)

major

Mitragynine inhibits CYP2D6, potentially altering metabolism of many common medications.

CNS depressants (benzodiazepines, alcohol, opioids)

major

Additive sedation and respiratory depression risk. Most reported kratom-associated fatalities involved co-ingestion.

View full interaction database

COA Connection

Appears on Certificates of Analysis as: MIT. Graded under P_acc (Potency Accuracy) (40% of total score).

View graded products

Cited Literature

[1]

Kruegel AC, Grundmann O (2018). The medicinal chemistry and neuropharmacology of kratom: A preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology.

DOI: 10.1016/j.neuropharm.2017.08.026

[2]

Váradi A, Marrone GF, Palmer TC, et al. (2016). Mitragynine/corynantheidine pseudoindoxyls as opioid analgesics with mu agonism and delta antagonism, which do not recruit β-arrestin-2. J Am Chem Soc.

DOI: 10.1021/jacs.6b00360

[3]

Prozialeck WC, Jivan JK, Andurkar SV (2012). Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc.

DOI: 10.7556/jaoa.2012.112.12.792

[4]

Singh D, Narayanan S, Vicknasingam B (2016). Traditional and non-traditional uses of Mitragynine (Kratom): A survey of the literature. Brain Res Bull.

DOI: 10.1016/j.brainresbull.2016.05.004

[5]

León F, Obeng S, Bhowmik S, et al. (2021). Activity of Mitragyna speciosa ("Kratom") alkaloids at serotonin receptors. J Med Chem.

DOI: 10.1016/j.ejphar.2021.174050

[6]

Eastlack SC, Cornett EM, Kaye AD (2020). Kratom — Pharmacology, clinical implications, and outlook: A comprehensive review. Pain Ther.

DOI: 10.1007/s40122-020-00151-x

[7]

Swogger MT, Walsh Z (2018). Kratom use and mental health: A systematic review. Drug Alcohol Depend.

DOI: 10.1016/j.drugalcdep.2018.10.006

[8]

Henningfield JE, Fant RV, Wang DW (2018). The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research. Psychopharmacology.

DOI: 10.1007/s00213-018-5010-2

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