Hermetica Superfood Encyclopedia
The Short Answer
Mitragynine is the primary psychoactive alkaloid found in kratom (Mitragyna speciosa), accounting for up to 66% of the plant's alkaloid content. It acts as a partial agonist at mu-opioid receptors while also interacting with adrenergic and serotonergic pathways.
CategoryNamed Bioactive Compounds
GroupCompound
Evidence LevelModerate
Primary Keywordmitragynine benefits
Synergy Pairings3
Mitragynine — botanical close-up
Health Benefits
Origin & History
Natural habitat
Mitragynine is the primary alkaloid found in the leaves of Mitragyna speciosa (kratom), a tropical tree native to Southeast Asia. It belongs to the indole alkaloid chemical class, specifically a Corynanthe-type alkaloid, and is typically extracted from kratom leaves via solvent-based methods followed by purification.
“Mitragynine from kratom leaves has been used in Southeast Asian traditional medicine (Thai and Malaysian folk systems) for centuries to manage pain, opioid withdrawal, and fatigue. Historical use includes both stimulant effects at low doses and sedative effects at high doses.”Traditional Medicine
Scientific Research
Clinical evidence is limited to a single phase 1 safety study (n=15 healthy volunteers) testing 5-40mg doses, which found no serious adverse events but minor vital sign changes. No RCTs, meta-analyses, or larger trials on efficacy for pain, withdrawal, or other therapeutic uses have been conducted. Most evidence remains preclinical, suggesting analgesic potential and reduced drug self-administration in animal models.
Preparation & Dosage
Traditional preparation
Clinically studied doses in the phase 1 trial were single oral administrations of 5mg, 10mg, 20mg, and 40mg of pure mitragynine, with peak plasma concentrations of ~5.7-25.6 ng/mL at 1 hour. No data exists on repeated dosing, extracts, powders, or standardization in human trials. Consult a healthcare provider before starting any new supplement.
Nutritional Profile
Mitragynine is the principal indole alkaloid of Kratom (Mitragyna speciosa), typically comprising 12–66% of total leaf alkaloid content. A dried kratom leaf contains roughly 1–2% total alkaloids by weight, with mitragynine concentrations ranging from approximately 5–20 mg per gram of dried leaf depending on strain and origin. It is a terpenoid indole alkaloid (molecular formula C₂₃H₃₀N₂O₄, MW 398.5) and acts primarily as a partial agonist at mu-opioid receptors and an antagonist/weak partial agonist at delta- and kappa-opioid receptors. It also interacts with adrenergic (alpha-2), serotonergic (5-HT₂A, 5-HT₂C), and dopaminergic pathways. Oral bioavailability in animal models is estimated at approximately 20–30%, with extensive first-pass hepatic metabolism via CYP3A4 and CYP2D6 to yield the more potent metabolite 7-hydroxymitragynine. It contains no meaningful macronutrients, vitamins, minerals, fiber, or protein. Plasma half-life in humans is estimated at approximately 23–24 hours based on limited phase 1 data.
How It Works
Mechanism of Action
Mitragynine functions as a partial agonist at mu-opioid receptors (MOR) and delta-opioid receptors, producing analgesic effects without full opioid receptor activation. It also modulates alpha-2 adrenergic receptors and 5-HT2A serotonin receptors, contributing to its complex pharmacological profile. The compound undergoes hepatic metabolism to 7-hydroxymitragynine, a more potent opioid receptor agonist.
Clinical Evidence
Human clinical evidence for mitragynine remains extremely limited, with only one phase 1 safety trial conducted in healthy volunteers. This small study (n=12) showed slight increases in impulsivity measures but no serious adverse events at single doses up to 44.1mg. No controlled trials have evaluated mitragynine for pain management or opioid withdrawal despite extensive preclinical research. Most evidence comes from observational studies and case reports of kratom use rather than isolated mitragynine research.
Safety & Interactions
Mitragynine may cause dose-dependent side effects including nausea, constipation, dizziness, and sedation similar to other opioid receptor agonists. The compound is metabolized by CYP3A4 enzymes, creating potential for drug interactions with CYP3A4 inhibitors or inducers. Regular use may lead to tolerance and physical dependence, with withdrawal symptoms reported upon discontinuation. Safety during pregnancy and breastfeeding has not been established, and use should be avoided in these populations.
Synergy Stack
Hermetica Formulation Heuristic
Also Known As
7-hydroxymitragynine precursorKratom alkaloidMitragyna speciosa extractBiak-biak compoundKetum alkaloidSpeciogynine derivative9-Methoxycorynantheidine
Frequently Asked Questions
What is the difference between mitragynine and 7-hydroxymitragynine?
Mitragynine is the parent compound and primary alkaloid in kratom, while 7-hydroxymitragynine is its metabolite formed in the liver. 7-hydroxymitragynine is approximately 13-17 times more potent at opioid receptors than mitragynine and contributes significantly to kratom's opioid-like effects.
How much mitragynine is typically found in kratom products?
Mitragynine concentrations in kratom products vary widely, typically ranging from 7-44mg per gram of dried leaf material. Commercial kratom extracts may contain much higher concentrations, sometimes standardized to specific mitragynine percentages, though quality control varies significantly between manufacturers.
Can mitragynine cause addiction or withdrawal symptoms?
Yes, mitragynine can potentially cause physical dependence and addiction due to its opioid receptor activity. Users may experience withdrawal symptoms including muscle aches, irritability, mood changes, and cravings when discontinuing regular use, though symptoms are generally milder than traditional opioid withdrawal.
What are the main side effects of mitragynine?
Common side effects include nausea, constipation, dizziness, dry mouth, and sedation at higher doses. Some users report stimulant-like effects at lower doses including increased energy and alertness. Serious adverse events are rare but may include respiratory depression at very high doses.
Is mitragynine legal in the United States?
Mitragynine's legal status varies by state and is subject to ongoing regulatory review. While not federally scheduled, several states have banned kratom and its alkaloids including mitragynine. The FDA has issued warnings about kratom products but has not approved mitragynine for any medical use.
Does mitragynine interact with opioid medications or other pain relievers?
Mitragynine may interact with opioid medications due to overlapping receptor activity, though clinical interaction studies are limited. Concurrent use with opioids, benzodiazepines, or other CNS depressants could theoretically increase sedation or respiratory depression risk. Anyone taking prescription pain medications or CNS-active drugs should consult a healthcare provider before using mitragynine-containing products.
Is mitragynine safe during pregnancy or breastfeeding?
Mitragynine safety during pregnancy and breastfeeding has not been established through clinical research, and its use is not recommended in these populations. Limited preclinical data exists on how mitragynine crosses the placenta or transfers into breast milk. Pregnant or nursing individuals should avoid mitragynine products and consult healthcare providers about safe alternatives for symptom management.
What does the clinical evidence actually show about mitragynine's effectiveness?
Most evidence for mitragynine comes from traditional use reports and preclinical laboratory studies rather than rigorous human trials. Only one Phase 1 safety trial in humans has been published, which tested tolerability but not therapeutic efficacy. For pain management and opioid withdrawal support—the most commonly cited uses—there are no completed randomized controlled trials in humans, limiting definitive claims about effectiveness.
Explore the Full Encyclopedia
7,400+ ingredients researched, verified, and formulated for optimal synergy.
Browse IngredientsThese statements have not been evaluated by the Food and Drug Administration. This content is for informational purposes only and is not intended to diagnose, treat, cure, or prevent any disease.
hermetica-encyclopedia-canary-zzqv9k4w mitragynine curated by Hermetica Superfoods at ingredients.hermeticasuperfoods.com and licensed CC BY-NC-SA 4.0 (non-commercial share-alike, attribution required)
