What is the difference between mitragynine and 7-hydroxymitragynine?

Mitragynine is the parent compound and the dominant alkaloid by mass in kratom leaf. 7-hydroxymitragynine is its hepatic metabolite, formed when CYP3A4 oxidizes mitragynine in the liver. In published in vitro assays, 7-OH binds the mu-opioid receptor with roughly 5 to 22 times higher affinity than mitragynine.

Is mitragynine the only active alkaloid in kratom?

No. Kratom contains more than 40 identified alkaloids. Mitragynine and 7-hydroxymitragynine receive the most attention in published pharmacology because of their abundance and receptor activity, but secondary alkaloids including paynantheine, speciogynine, speciociliatine, and mitragynine pseudoindoxyl have measurable receptor activity in laboratory assays.

Is mitragynine a controlled substance in the United States?

Mitragynine is not currently scheduled federally in the United States. The DEA's 2016 notice of intent to schedule was withdrawn. The FDA's 2025 Schedule I recommendation specifically targeted 7-hydroxymitragynine; mitragynine itself was not the subject of that recommendation. State and municipal restrictions vary, so verify in your jurisdiction.

What does "active metabolite" mean for mitragynine?

An active metabolite is a metabolic product of a parent compound that retains pharmacological activity. 7-hydroxymitragynine is described as an active metabolite of mitragynine because CYP3A4-mediated conversion in the liver generates it from oral mitragynine, and 7-OH itself binds mu-opioid receptors with greater affinity than mitragynine.

Where can I read peer-reviewed mitragynine research?

Notable journals publishing mitragynine research include the Journal of Medicinal Chemistry, ACS Central Science, the Journal of Natural Products, Bioorganic and Medicinal Chemistry, Phytochemistry, and Drug and Alcohol Dependence. Most papers are indexed in PubMed (pubmed.ncbi.nlm.nih.gov).

Why does FDA scrutiny focus on 7-OH and not on mitragynine?

FDA's specific concern, articulated in warning letters and in the July 2025 recommendation to the DEA, focuses on isolated and concentrated 7-hydroxymitragynine products rather than on mitragynine. The agency has cited the much higher receptor affinity of 7-OH and the rise of products that concentrate 7-OH well above natural leaf levels as the basis for that focus.

Alkaloids & Chemistry

Mitragynine

At-a-glance comparison

Spec	Value
Compound class	Indole alkaloid (corynantheine type)
Source	Mitragyna speciosa (kratom) leaves
Typical leaf abundance	Approximately 50-66% of total alkaloid content (varies by strain, harvest, and processing)
Molecular formula	C23H30N2O4
Molar mass	398.50 g/mol
CAS Registry Number	4098-40-2
Active metabolite	7-Hydroxymitragynine (via hepatic CYP3A4)
U.S. FDA status	Not approved for any medical use

What is mitragynine?

Mitragynine is the dominant indole alkaloid produced by Mitragyna speciosa, an evergreen tree native to Southeast Asia. Among the 40-plus alkaloids identified in kratom leaf, mitragynine is by far the most abundant; published HPLC quantification typically places it between 50% and 66% of total alkaloid content, depending on strain, harvest conditions, and post-harvest handling.

Structurally, mitragynine belongs to the corynantheine subclass of indole alkaloids - compounds built on the indole ring system that also includes the related kratom alkaloids paynantheine, speciogynine, and speciociliatine. The molecular formula is C23H30N2O4 and the molar mass is 398.50 g/mol.

Where does mitragynine occur in nature?

Mitragynine is biosynthesized in the leaves of Mitragyna speciosa. The species is native to Thailand, Malaysia, Indonesia, Borneo, and Papua New Guinea, with commercial cultivation concentrated in Indonesia. The compound was first isolated and chemically characterized in the mid-twentieth century, with sustained pharmacology research continuing in Japan in the 1970s. Broad scientific attention resumed in the 2000s and accelerated through the 2010s and 2020s as analytical and receptor-pharmacology tools advanced.

Pharmacology in research context

Mitragynine has also been studied at the delta-opioid receptor, kappa-opioid receptor, alpha-2 adrenergic receptors, and several serotonin receptor subtypes in published assays, with varying affinities and mixed agonist/antagonist behavior depending on the assay system used.

These findings come from cell-based and biochemical assays performed in academic and industry laboratories. They describe receptor-level interactions only and should not be interpreted as evidence of safety, efficacy, or any clinical or therapeutic effect in humans.

Relationship to 7-hydroxymitragynine

Mitragynine is converted in the liver to 7-hydroxymitragynine (7-OH) through oxidation by the cytochrome P450 enzyme CYP3A4. 7-OH is itself a partial MOR agonist, with receptor binding affinity reported at roughly 5 to 22 times that of mitragynine in published in vitro assays.

Because of this first-pass metabolism, 7-OH is described in the scientific literature as an active metabolite of mitragynine. Even though 7-OH is present at only trace concentrations in fresh kratom leaf, it contributes substantially to the in vivo pharmacological profile of orally consumed kratom material in research models. CYP3A4 inhibitors such as ketoconazole reduce 7-OH formation in those research models, while CYP3A4 inducers may increase it.

How is mitragynine measured in commercial products?

Mitragynine content in commercial kratom and 7-OH products is typically measured by reverse-phase high-performance liquid chromatography (HPLC), often with ultraviolet or mass-spectrometry detection. A complete Certificate of Analysis (COA) reports mitragynine as a percent-assay value alongside test results for microbial counts, heavy metals, residual solvents, and - for finished products - the percent-assay of 7-hydroxymitragynine.

Industry-standard analytical methods follow guidance documents from the United States Pharmacopeia (USP), AOAC International, and the International Council for Harmonisation (ICH). The American Kratom Association GMP Standards Program specifies test panels for member vendors.

Regulatory status (educational summary; verify in your jurisdiction)

The U.S. Food and Drug Administration (FDA) has not approved mitragynine or kratom for any medical use. Mitragynine and kratom remain federally legal in most U.S. states as of May 2026, although several states and municipalities prohibit kratom and 7-OH products and others impose age or labeling requirements.

The U.S. Drug Enforcement Administration (DEA) issued a notice of intent in August 2016 to emergency-schedule mitragynine and 7-OH as Schedule I controlled substances, but the agency withdrew that proposal in October 2016 following public response. In July 2025 the FDA recommended Schedule I status specifically for 7-hydroxymitragynine; mitragynine itself was not the subject of that recommendation. As of May 2026, no final DEA action on the 2025 recommendation had been published.

Verify the current legal status of mitragynine and kratom in your jurisdiction before any purchase. This summary is educational and does not constitute legal advice.

Common questions about mitragynine

What is the difference between mitragynine and 7-hydroxymitragynine?: Mitragynine is the parent compound and the dominant alkaloid by mass in kratom leaf. 7-hydroxymitragynine is its hepatic metabolite, formed when CYP3A4 oxidizes mitragynine in the liver. In published in vitro assays, 7-OH binds the mu-opioid receptor with roughly 5 to 22 times higher affinity than mitragynine.
Is mitragynine the only active alkaloid in kratom?: No. Kratom contains more than 40 identified alkaloids. Mitragynine and 7-hydroxymitragynine receive the most attention in published pharmacology because of their abundance and receptor activity, but secondary alkaloids including paynantheine, speciogynine, speciociliatine, and mitragynine pseudoindoxyl have measurable receptor activity in laboratory assays.
How is mitragynine measured in commercial products?: Reverse-phase HPLC with ultraviolet or mass-spectrometry detection is the analytical standard. A complete Certificate of Analysis reports mitragynine as a percent-assay value along with microbial, heavy-metal, and residual-solvent test results.
Is mitragynine a controlled substance in the United States?: Mitragynine is not currently scheduled federally in the United States. The DEA's 2016 notice of intent to schedule was withdrawn. The FDA's 2025 Schedule I recommendation specifically targeted 7-hydroxymitragynine; mitragynine itself was not the subject of that recommendation. State and municipal restrictions vary, so verify in your jurisdiction.
What does "active metabolite" mean for mitragynine?: An active metabolite is a metabolic product of a parent compound that retains pharmacological activity. 7-hydroxymitragynine is described as an active metabolite of mitragynine because CYP3A4-mediated conversion in the liver generates it from oral mitragynine, and 7-OH itself binds mu-opioid receptors with greater affinity than mitragynine.
Where can I read peer-reviewed mitragynine research?: Notable journals publishing mitragynine research include the Journal of Medicinal Chemistry, ACS Central Science, the Journal of Natural Products, Bioorganic and Medicinal Chemistry, Phytochemistry, and Drug and Alcohol Dependence. Most papers are indexed in PubMed (pubmed.ncbi.nlm.nih.gov).
Why does FDA scrutiny focus on 7-OH and not on mitragynine?: FDA's specific concern, articulated in warning letters and in the July 2025 recommendation to the DEA, focuses on isolated and concentrated 7-hydroxymitragynine products rather than on mitragynine. The agency has cited the much higher receptor affinity of 7-OH and the rise of products that concentrate 7-OH well above natural leaf levels as the basis for that focus.

References

Singh D, Müller CP, Vicknasingam BK. (2016). Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug and Alcohol Dependence. PMID 24667060.
Kruegel AC, Grundmann O. (2018). The medicinal chemistry and neuropharmacology of kratom. Neuropharmacology. PMID 29132958.
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. Journal of Medicinal Chemistry. PMID 27513560.
Wilson LL, Harris HM, Eans SO, et al. (2020). Lyophilized kratom tea as a therapeutic option for opioid dependence. Drug and Alcohol Dependence.
Hassan Z, Muzaimi M, Navaratnam V, et al. (2013). From kratom to mitragynine and its derivatives. Neuroscience and Biobehavioral Reviews. PMID 23206666.
Kamble SH, Sharma A, King TI, et al. (2020). Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids. Toxicology Letters.

Important safety information:

Products containing 7-hydroxymitragynine (7-OH) are sold for adult use only (21+). These statements have not been evaluated by the U.S. Food and Drug Administration. Products are not intended to diagnose, treat, cure, or prevent any disease. The FDA has raised safety concerns regarding concentrated 7-OH products; consult a qualified healthcare professional before use. Do not operate vehicles or machinery after use. Keep out of reach of children and pets. Laws vary by state, buyers are responsible for knowing applicable law.