Where is mitragynine pseudoindoxyl found in nature?

Only at trace concentrations in Mitragyna speciosa material. Most published research on the compound uses chemically synthesized material derived from corynantheidine-class precursors.

Who first characterized mitragynine pseudoindoxyl?

The most influential published characterization is Váradi and colleagues (2016) in the Journal of Medicinal Chemistry, which described synthesis and the G-protein-biased MOR partial-agonist receptor profile.

Is mitragynine pseudoindoxyl in commercial 7-OH products?

Quantification of mitragynine pseudoindoxyl in commercial products is challenging due to low natural abundance and is not a routine Certificate of Analysis test panel item. Confirm specific product composition with the manufacturer's COA and the issuing laboratory.

Does the FDA's July 2025 Schedule I recommendation include mitragynine pseudoindoxyl?

The FDA's July 2025 recommendation to the DEA specifically named 7-hydroxymitragynine. As of May 2026, no separate scheduling action targeting mitragynine pseudoindoxyl had been published. Verify current status in your jurisdiction.

Alkaloids & Chemistry

Mitragynine Pseudoindoxyl

At-a-glance comparison

Spec	Value
Compound class	Indole alkaloid; pseudoindoxyl rearrangement product
Source	Trace constituent of Mitragyna speciosa material; rearrangement product of 7-hydroxymitragynine
Receptor target (in vitro)	Mu-opioid receptor - G-protein-biased partial agonist; delta-opioid receptor antagonist
Affinity vs 7-OH at MOR	Higher (typically reported as 5-10x in published assays)
Natural abundance	Very low; most commonly produced via chemical rearrangement of 7-OH in research settings
Primary published characterization	Váradi et al. 2016 (J Med Chem)

What is mitragynine pseudoindoxyl?

Mitragynine pseudoindoxyl is a chemical rearrangement product of 7-hydroxymitragynine. The pseudoindoxyl skeleton arises from oxidative ring rearrangement of the indole core present in 7-OH and other kratom alkaloids. The compound is present at very low concentrations in fresh kratom material - too low for direct isolation at meaningful scale - and is most commonly studied as a chemically synthesized or derivatized reference compound in receptor-pharmacology research.

The most influential published characterization of mitragynine pseudoindoxyl is Váradi and colleagues (2016), which described both its synthesis from corynantheidine-class precursors and its receptor profile.

Pharmacology in research context

In Váradi 2016 and subsequent in vitro characterizations, mitragynine pseudoindoxyl binds the mu-opioid receptor with affinity higher than 7-hydroxymitragynine - typically reported as roughly five to ten times greater across published assay systems - and shows G-protein-biased signaling, preferentially activating G-protein pathways over β-arrestin recruitment. At the delta-opioid receptor, the compound is generally reported as an antagonist.

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

How mitragynine pseudoindoxyl relates to 7-OH and mitragynine

The three compounds form a chemical and pharmacological progression: mitragynine is the parent alkaloid abundant in kratom leaf; CYP3A4 hepatic oxidation produces 7-hydroxymitragynine, which has higher MOR affinity than mitragynine; further oxidative rearrangement produces mitragynine pseudoindoxyl, which has higher MOR affinity than 7-OH. All three are characterized in published work as G-protein-biased partial agonists at MOR, but their binding affinities and abundances are markedly different.

Whether and to what extent mitragynine pseudoindoxyl forms in vivo from 7-OH in humans is an active research question. Quantification of the compound in commercial products is challenging because of its low natural abundance and is not a routine COA test.

Common questions about mitragynine pseudoindoxyl

What is mitragynine pseudoindoxyl?: It is a rearrangement product of 7-hydroxymitragynine. The pseudoindoxyl skeleton arises from oxidative rearrangement of the indole core present in 7-OH. The compound has been characterized in published in vitro work as a high-affinity G-protein-biased partial mu-opioid receptor agonist.
Is mitragynine pseudoindoxyl stronger than 7-OH?: In published in vitro receptor-binding assays, mitragynine pseudoindoxyl shows higher mu-opioid receptor affinity than 7-OH - typically reported as roughly five to ten times greater. Direct potency comparisons are research-context observations from receptor assays, not clinical equivalence statements.
Where is mitragynine pseudoindoxyl found in nature?: Only at trace concentrations in Mitragyna speciosa material. Most published research on the compound uses chemically synthesized material derived from corynantheidine-class precursors.
Who first characterized mitragynine pseudoindoxyl?: The most influential published characterization is Váradi and colleagues (2016) in the Journal of Medicinal Chemistry, which described synthesis and the G-protein-biased MOR partial-agonist receptor profile.
Is mitragynine pseudoindoxyl in commercial 7-OH products?: Quantification of mitragynine pseudoindoxyl in commercial products is challenging due to low natural abundance and is not a routine Certificate of Analysis test panel item. Confirm specific product composition with the manufacturer's COA and the issuing laboratory.
Does the FDA's July 2025 Schedule I recommendation include mitragynine pseudoindoxyl?: The FDA's July 2025 recommendation to the DEA specifically named 7-hydroxymitragynine. As of May 2026, no separate scheduling action targeting mitragynine pseudoindoxyl had been published. Verify current status in your jurisdiction.

References

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.
Kruegel AC, Gassaway MM, Kapoor A, et al. (2016). Synthetic and receptor signaling explorations of the Mitragyna alkaloids. JACS.
Hemby SE, McIntosh S, Leon F, et al. (2018). Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids. Addiction Biology.
Hassan Z, Muzaimi M, Navaratnam V, et al. (2013). From kratom to mitragynine and its derivatives. Neuroscience and Biobehavioral Reviews. PMID 23206666.

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.