Mitragynine (Kratom)
Mitragynine is the primary active alkaloid in kratom (Mitragyna speciosa), a partial mu-opioid receptor agonist with dose-dependent stimulant (low dose) to opioid-like sedative/analgesic (higher dose) effects. It carries documented risks of dependence, withdrawal, hepatotoxicity, and cardiac effects.
Evidence last reviewed: 02 Aug 2026
Not a routine supplement — not recommended for self-directed use.
Information here is educational only, not a recommendation to use. See our Safety page.
- •Anyone with a current or past opioid use disorder or other substance dependence history
- •Pregnant or breastfeeding individuals — opioid-like neonatal withdrawal has been reported following maternal kratom use
- •Anyone taking opioids, benzodiazepines, alcohol, or other CNS depressants — additive respiratory depression risk
- •Anyone with liver disease or a history of drug-induced liver injury
- •Anyone with cardiac arrhythmia, QT prolongation, or taking QT-prolonging medications
- •Anyone taking MAOIs, SSRIs, or SNRIs — kratom alkaloids affect monoaminergic pathways in addition to opioid receptors
- •Anyone under 18
- •Anyone in a jurisdiction where kratom or its alkaloids are restricted or banned — check local regulations before use
Partial agonist at mu-opioid receptors (with additional activity at delta/kappa opioid receptors and adrenergic/monoaminergic systems), producing biphasic effects: stimulant/euphoric at low doses, sedative/analgesic/opioid-like at higher doses. Partially metabolized to 7-hydroxymitragynine, a minor but substantially more potent mu-opioid agonist metabolite.
Evidence is from research or clinical settings — does not imply safety outside supervised contexts.
Evidence for mitragynine is a mix of receptor pharmacology, clinical case reports/series, and epidemiological review — there are no controlled human efficacy trials. The safety literature (dependence, hepatotoxicity, cardiotoxicity, poison-control exposure trends) is comparatively well developed and consistent across sources.
Mu-opioid receptor partial agonism (mechanism of action)In vitro receptor-binding assays · Receptor pharmacologyModerate
Establishes mitragynine as an atypical, G-protein-biased partial agonist at the mu-opioid receptor with additional activity at delta/kappa opioid and adrenergic receptors — the structural basis for its dose-dependent stimulant-to-opioid-like effects.
7-Hydroxymitragynine identified as the primary mediator of analgesic effectsAnimal models · PharmacologyModerate
Shows that 7-hydroxymitragynine — a minor alkaloid and active metabolite of mitragynine — is substantially more potent at the mu-opioid receptor and accounts for most of kratom's analgesic effect. Directly relevant to the elevated risk of concentrated 7-OH-mitragynine products.
Kratom use disorder and opioid-like withdrawal syndromeRegular kratom users · Clinical reviewModerate
Documents a clinically recognized kratom use disorder, with a withdrawal syndrome on cessation resembling mild-to-moderate opioid withdrawal (myalgia, insomnia, anxiety, GI distress, cravings).
Withdrawal/dependence treated with opioid-agonist therapyCase series · Case series + systematic reviewLow
Describes successful treatment of kratom dependence and withdrawal using buprenorphine/naloxone, underscoring the clinically opioid-like nature of kratom dependence.
Cholestatic / acute liver injuryCase reports · Case reportLow
Case report of cholestatic liver injury temporally associated with kratom use, resolving after discontinuation — one of several published kratom-associated liver injury cases.
Cardiac hERG channel inhibition (QT-prolongation risk)In vitro (HEK293 cells) · In vitro pharmacologyLow
Mitragynine inhibits hERG1a/1b potassium channels in vitro — a mechanism associated with QT-interval prolongation and arrhythmia risk, consistent with published cardiotoxicity case reports.
Association with fatalities, largely in poly-substance contextsUS poison control / medical examiner data · Epidemiological reviewLow
Reports on kratom-involved deaths recorded by US poison control centers and medical examiners, most involving co-ingestion with other substances — underscoring the danger of combining kratom with other CNS-active drugs.
Forms & usage▾
Safety & trade-offs5▾
Dependence & withdrawal potential
Context: Regular, especially daily, use is associated with a well-documented withdrawal syndrome resembling mild opioid withdrawal.
Hepatotoxicity (liver injury) case reports
Context: Multiple published case reports of cholestatic and acute liver injury following kratom use.
Additive CNS/respiratory depression with opioids, benzodiazepines, alcohol
Cardiac QT-prolongation / hERG channel inhibition reported
Highly variable, often unverified alkaloid content in commercial products
●High ●Moderate ● Low / note