Mitragynine

methyl (E)-2-[(2S,3S,12bS)-3-ethyl-8-methoxy-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizin-2-yl]-3-methoxyprop-2-enoate

Overview

Mitragynine belongs to Opioids.

Key safety note: Mitragynine is the main alkaloid of kratom, which has a genuinely dual profile: a mild stimulant at low doses and an opioid at higher ones.[4][6]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • Low doses (≈1–5 g leaf): caffeine-like stimulation, alertness, increased energy, focus, talkativeness and sociability.
  • Higher doses (≈5–8 g+): opioid-like analgesia, calm, mild euphoria, sedation and anxiety relief: often with the stimulant and relaxant qualities felt together.
  • Common unwanted effects: nausea, vomiting, constipation, sweating, itching, dizziness and, on stopping after regular use, an opioid-type withdrawal (irritability, aches, runny nose, insomnia, craving).
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral: dried leaf chewed, brewed as tea, or swallowed as powder/capsules. Also concentrated extracts. Figures below are for KRATOM LEAF (mitragynine is not dosed in isolation) and are rough context, not a safe or recommended amount.. Kratom is dosed as leaf/powder, and its effect is biphasic: more stimulating at lower doses, more opioid-like (sedating, analgesic) at higher ones. Potency varies widely between products, and concentrated extracts (and 'enriched 7-OH' products) can be far stronger than leaf, so the same gram figure is not comparable across products. Key harm-reduction points: never combine with opioids, benzodiazepines, alcohol or other depressants (the main cause of kratom-associated deaths). Start low with a known product. Expect tolerance and dependence with daily use, and be aware that naloxone reverses the opioid component. Amounts refer to dried leaf.

Dose ranges

Threshold

1 g leaf

Light (stimulant)

2–3 g

Common

3–5 g

Strong (opioid-like)

5–8 g

Heavy

8 g +

Duration

onset

20–40 min

total

2–4 h

after effects

3–6 h

Chemical & Physical Properties
FormulaC23H30N2O4
Molar mass398.5 g/mol
StateSolid
Melting point104 °C
Boiling point235 °C at 5 mmHg
DensityNot reported
Vapor pressureNot reported
pKaNot reported
LogP3.4 (predicted, XLogP3)
SolubilitySoluble in alcohol, chloroform, acetic acid
Refractive indexNot reported
Identifiers & Synonyms
CAS4098-40-2
CAS (enantiomer)
PubChem CID3034396
InChIKeyLELBFTMXCIIKKX-QVRQZEMUSA-N
InChIInChI=1S/C23H30N2O4/c1-5-14-12-25-10-9-15-21-18(7-6-8-20(21)28-3)24-22(15)19(25)11-16(14)17(13-27-2)23(26)29-4/h6-8,13-14,16,19,24H,5,9-12H2,1-4H3/b17-13+/t14-,16+,19+/m1/s1
SMILESCC[C@@H]1CN2CCC3=C([C@@H]2C[C@@H]1/C(=C\OC)/C(=O)OC)NC4=C3C(=CC=C4)OC

Synonyms

  • Kratom
  • Kratom alkaloid
  • 9-methoxycorynantheidine
Pharmacodynamics & Biochemistry

Mitragynine is the most abundant alkaloid of kratom (Mitragyna speciosa), a Southeast-Asian tree whose leaves are chewed or brewed for stimulant and opioid-like effects. It is a corynanthe-type indole alkaloid that binds the μ-opioid receptor (MOR) only weakly (Kᵢ ≈7,700 nM: roughly a hundred-fold weaker than its metabolite 7-hydroxymitragynine, ≈78 nM) and is a low-efficacy ligand there: it behaves as a weak, G-protein-biased partial agonist in some assays and as an antagonist in [³⁵S]GTPγS binding, with weaker activity at the κ- and δ-opioid receptors. Much of kratom's actual opioid effect in the body is therefore thought to be carried by 7-hydroxymitragynine, formed from mitragynine by hepatic CYP3A4, which is a far more potent MOR partial agonist. This is why the parent alkaloid's weak, assay-dependent receptor activity understates kratom's opioid pharmacology in vivo. Mitragynine is not a pure opioid: it also acts at α2-adrenergic and several serotonin (5-HT) receptors and modulates other targets, which is thought to underlie kratom's dose-dependent, biphasic profile: caffeine-like stimulation, focus and sociability at low doses, shifting to analgesia, sedation and euphoria at higher doses. (Because mitragynine binds MOR weakly and its functional efficacy is low and assay-dependent, the sub-nanomolar 'agonist' potency listed for it in one curated dataset is not shown here, it would misrepresent this pharmacology, the honest weak binding affinity is given instead.)

Biological targets

  • MOR

Binding & functional measurements

TargetMeasurementSpecies
MORKi 7,700 nMHuman/Rodent
Pharmacokinetics
BioavailabilityOral, variable
Tmax≈0.8–1.5 h
Half-life≈3–9 h (estimates vary)
VdNot reported
Protein bindingNot reported
MetabolismHepatic CYP3A4. O-demethylation to active 7-hydroxymitragynine
ExcretionRenal and biliary
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Mitragynine is the main alkaloid of kratom, which has a genuinely dual profile: a mild stimulant at low doses and an opioid at higher ones. Its most important risk is opioid-type: tolerance, physical dependence and a real (if usually milder-than-classical-opioid) withdrawal syndrome develop with regular use, and respiratory depression can occur: the danger rises sharply when kratom is combined with other depressants (opioids, benzodiazepines, alcohol, gabapentinoids), which is the pattern in most kratom-associated deaths. Product quality is a major hazard: powders and especially concentrated extracts vary widely in alkaloid content, are sometimes adulterated (e.g. with O-desmethyltramadol in the past), and 'enriched 7-OH' products can deliver a far larger opioid dose than leaf. Common effects include nausea, constipation, sweating, itching, dizziness and, with heavy use, weight loss and dependence. It should not be combined with other depressants or used in pregnancy. Naloxone can reverse the opioid component. Isolated deaths from kratom alone are rare and usually involve very high doses or polydrug use.[4][6]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

Opioids, Benzodiazepines, Alcohol Additive sedation and respiratory depression, the pattern in most kratom-associated deaths.[4]
CYP3A4 inhibitors (ritonavir, azole antifungals, macrolides, grapefruit) Azole antifungals, ritonavir or grapefruit increase mitragynine exposure and effect.[3]
MAOIs, SSRIs, Stimulants (amphetamines, cocaine) Implicated in adverse events, with a theoretical serotonin-toxicity and additive cardiovascular risk.[4]
CYP2D6 substrate drugs Mitragynine can inhibit several CYP enzymes in vitro, a possible source of herb-drug interactions.[3]

Contraindications

Combining with alcohol or other CNS depressants concurrent opioid or other CNS-depressant use.[4]
Pregnancy or breastfeeding[4]
Kidney or liver impairment significant hepatic impairment.[4]
History of stimulant or substance use disorder history of opioid or other substance use disorder.[4]
Usage & Context
  • Traditionally used in Thailand, Malaysia and Indonesia, leaves chewed, or brewed as a tea, by manual labourers for stimulation and endurance and in folk medicine for pain, diarrhoea and cough.
  • In the West it is widely used as an over-the-counter herbal product for pain, anxiety, low mood and energy, and notably for self-managed treatment of opioid withdrawal and reduction of opioid or alcohol use.
  • Also used recreationally, and studied as a lead for atypical (potentially safer-profile) opioid analgesics. It sits in an unusual and shifting legal position between herbal supplement and controlled drug.
Sources & Evidence

Further Information