Chemistry & Detection Reference

This clinician-facing working reference covers pharmacologically active kratom alkaloids and metabolites, metabolic pathways, emerging semisynthetic analogues, and biological detection. Its internal bracketed numbers refer to the plain numbered source list at the foot of this page; they are not entries in the site evidence registry.

Important: CYP assignments above come from recombinant human CYP experiments and, for the MG to 7-OH step, are supported by a controlled itraconazole interaction study in healthy volunteers. Whole-body metabolism can involve additional enzymes and nonenzymatic chemistry. [1-4]

This compact index distinguishes categories for webpage implementation. Metabolite means formed biologically from another kratom alkaloid; botanical alkaloid means present in M. speciosa; and semisynthetic analogue means deliberately chemically modified from a kratom scaffold. Several compounds occupy more than one category.

The following table includes compounds with demonstrated pharmacologic activity after formation from a kratom alkaloid. It deliberately distinguishes human-confirmed metabolites from metabolites demonstrated only in human liver systems or preclinical animals.

These compounds are important for forensic interpretation and for understanding total exposure, but clinically meaningful pharmacologic activity has not been established for each one.

The following values are useful orientation numbers, not direct-purified-7-OH pharmacokinetics. In a controlled single-dose study of a standardized kratom product in healthy adults, median terminal half-lives were approximately: [5]

A separate controlled dried-leaf study found mean MG half-lives around 43 h after single dosing and 68 h after repeated dosing, while mean 7-OH estimates were roughly 5 h single-dose and 25 h repeated-dose in that study. [6]

A 2026 concentrated-mitragynine-extract study reported extremely variable 7-OH half-life estimates after repeated dosing, including much longer terminal estimates in the highest-dose cohort. The authors specifically cautioned that high-dose estimates may reflect complex formation/elimination kinetics and possible saturation. This is another reason not to use a single fixed 7-OH half-life clinically. [7]

Renal elimination

Unchanged renal excretion differs substantially across alkaloids. Mitragynine itself is only minimally recovered unchanged in urine, while some minor alkaloids have materially higher unchanged urinary fractions. Most overall disposition therefore cannot be summarized as “the kidneys simply clear intact kratom alkaloids.” Metabolism plus conjugation are important. [5]

Mitragynine pseudoindoxyl (MP) deserves its own category because it is simultaneously:

1. a downstream transformation product of 7-OH;
2. a potent opioid-active molecule in experimental pharmacology; and
3. an increasingly relevant semisynthetic/commercial compound in the 7-OH marketplace. [11-14,18]

Kamble and colleagues demonstrated that 7-OH rearranged rapidly in human plasma ex vivo, with approximately 53.8% conversion to MP after 120 minutes under their experimental conditions. MP itself remained comparatively stable during the experiment. Those are ex-vivo plasma stability data, not systemic human pharmacokinetics. [11,12]

More recent metabolic-networking work supports both liver-associated and nonenzymatic contributions to MP formation. Human in-vivo fractional conversion, oral bioavailability, volume of distribution, systemic half-life, renal/fecal clearance, and clinical detection window have not been established. [13]

For forensic interpretation, a positive MP result can be difficult to interpret without context because MP may represent direct use of an MP-containing product, downstream formation after 7-OH exposure, or both. Product analysis and analyte ratios may eventually help, but no universally validated clinical algorithm currently exists.

MGM-15

Preferred descriptive name: dihydro-7-hydroxymitragynine.
Common labels: MGM-15; DH7OH; some commercial material has used “DHM” terminology, which is chemically ambiguous.

• MGM-15 is a synthetic/semi-synthetic derivative of 7-OH, produced by reduction/saturation of the relevant imine/double-bond system in the mitragynine scaffold. [19,20]
• In receptor studies it shows strong opioid-receptor activity, including MOR and DOR activity. [19,20]
• A 2025 analytical report identified commercial tablets averaging about 10.9 mg MGM-15 per tablet in the products tested. [19]
• The Center for Forensic Science Research and Education reported first U.S. detection in 2025 and confirmed MGM-15 in drug material and toxicology specimens using LC-QTOF-MS with reference material. [21]
• GC-MS is problematic: MGM-15 can undergo analytical conversion to mitragynine during GC analysis, creating a serious identification pitfall. High-quality LC-MS confirmation is preferable. [21]
• Human pharmacokinetics, human metabolism, human half-life, and validated urine/blood detection window: unknown.
• Clinical withdrawal/overdose literature: essentially absent compared with 7-OH.

MGM-16

Description: fluorinated dihydro-7-OH analogue. Position numbering varies depending on chemical-nomenclature convention; the medicinal-chemistry literature describes it as a fluorinated analogue developed alongside MGM-15. [20,22]

• Developed in preclinical medicinal chemistry as a potent dual mu/delta opioid agonist. [20,22]
• Demonstrated antiallodynic/analgesic activity in animal models. [20,22]
• DEA's 2026 scheduling record discusses MGM-16 as an emerging related compound but reported no established consumer-market/toxicology presence comparable to 7-OH or MGM-15 at the time of the notice. [18]
• Human use studies, metabolism, half-life, urine/blood detection window: none established.
• Routine laboratory availability: no standard clinical assay.

3-dehydromitragynine (3DM / 3DMTG)

3DM belongs in two categories at once: it is an oxidative MG product demonstrated in metabolic systems, and it can also occur as a minor natural/commercial-product constituent. The 2021 oxidative-metabolism study demonstrated formation from MG by a non-CYP, NADPH-independent pathway in human liver microsomes/S9 and in mice, and characterized MOR partial-agonist activity plus high-dose toxicity in mice through a mechanism not fully explained by opioid receptors. [34]

A 2026 study additionally showed degradation of 7-OH to 3DM under simulated gastric conditions. This chemistry is relevant to oral products but does not establish the fraction of an oral 7-OH dose converted to 3DM in living humans. [35]

• Controlled human in-vivo confirmation: not established.
• Human PK / half-life / clearance: unknown.
• Routine toxicology detection: not standard; targeted HRMS can identify it with an appropriate standard.
• Validated urine/blood detection window: unknown.
• Commercial relevance: reported in contemporary product analyses, including products with complex/mislabeled alkaloid profiles. [36]

8-hydroxymitragynine and 11-hydroxymitragynine

These names appear in emerging commercial/analytical literature. They should be listed as related hydroxylated mitragynine compounds, not as established clinically important human metabolites unless a specific human metabolic study demonstrates that pathway. Human pharmacology, PK, half-life, and detection windows remain poorly characterized.

Research pseudoindoxyl / hydroxyl analogues

Medicinal-chemistry literature includes compounds such as 7-hydroxypaynantheine, 7-hydroxyspeciogynine, paynantheine pseudoindoxyl, and speciogynine pseudoindoxyl. These are useful for understanding structure-activity relationships but should not be presented to patients as established human metabolites or common retail exposures without direct evidence. [24]

Kratom contains dozens of indole and oxindole alkaloids. Modern analytical studies have structurally characterized more than forty, with counts varying by plant chemotype, analytical method, and what authors consider a distinct alkaloid. The following are the most relevant to a clinical 7-OH resource. [25,26]

Mitragynine (MG)

The predominant alkaloid in most kratom leaf products. Opioid-active itself but also functions as a metabolic precursor to 7-OH. It has a much longer terminal half-life than 7-OH in botanical exposure studies. Human MG metabolism is extensive; unchanged urinary excretion is low. [1-7]

7-hydroxymitragynine (7-OH)

Minor naturally occurring alkaloid, human MG metabolite, oxidation/processing product, and now a high-dose commercial drug. Potent opioid pharmacology. Direct high-dose purified human PK remains a major evidence gap. [1-7,18]

Mitragynine pseudoindoxyl (MP)

Potent rearrangement product of 7-OH and also a directly manufactured commercial compound. Human systemic PK remains unknown. [11-14,18]

Speciogynine

Common minor alkaloid. Parent compound has serotonergic receptor binding; its 9-O-desmethyl metabolite demonstrates functional 5-HT1A agonism. [15-17]

Paynantheine

Common minor alkaloid. Like speciogynine, it has serotonergic receptor interactions, while its 9-O-desmethyl metabolite shows functional 5-HT1A agonism. [15-17]

Speciociliatine

Stereoisomer/related indole alkaloid with opioid-receptor activity. Human PK has been measured after botanical kratom exposure. [5,25,26]

Mitraciliatine

Minor alkaloid present in some chemotypes; has opioid-receptor activity in modern screening studies. Human PK has been measured after botanical exposure. [5,25,26]

Isopaynantheine and epiallo-isopaynantheine

Minor alkaloids found in botanical kratom. Opioid-receptor activity has been reported for some members of this subgroup, including KOR activity in modern functional screens. Clinical contribution is uncertain. [25-27]

Corynantheidine

Minor alkaloid with opioid-receptor binding/antagonist-like pharmacology reported in preclinical work. It is relevant to the broader kratom targetome but is not a principal 7-OH metabolite.

Corynoxine A / corynoxine B / corynoxeine

Oxindole alkaloids present in some kratom samples. They are pharmacologically interesting but far less clinically characterized than MG or 7-OH. [25,26]

Speciofoline / isospeciofoline (and related spelling variants)

Minor alkaloids identified in modern phytochemical profiling. Clinical activity remains incompletely characterized. [25,26]

Rhynchophylline / 3-epirhynchophylline and related oxindoles

Minor botanical constituents. They are part of the broader kratom alkaloid profile but should not be conflated with 7-OH or its metabolic pathway. [25,26]

N-oxide alkaloids

Mitragynine-N(4)-oxide, speciociliatine-N(4)-oxide, isopaynantheine-N(4)-oxide, and related N-oxides have been identified in botanical material. Their abundance can be affected by storage/oxidation and product processing. Clinical pharmacologic significance is incompletely defined. [25,26]

Routine urine drug screens

A routine “opiates” immunoassay is generally designed around morphine-like structures and does not specifically identify mitragynine, 7-OH, MP, MGM-15, or MGM-16. A negative routine opioid screen therefore does not exclude kratom-family exposure.

Dedicated mitragynine immunoassays have been developed, but they are specialized assays and can cross-react with related alkaloids/metabolites. Confirmation by chromatography-mass spectrometry is preferred when compound-level identification matters. [28]

Targeted urine testing

Validated research/forensic methods include LC-MS/MS, LC-HRMS, LC-QTOF-MS, and capillary electrophoresis-MS/MS. A 2024 urine method reported analytical limits of detection of approximately 0.5 ng/mL for mitragynine and 2 ng/mL for 7-OH. These are analytical sensitivity limits, not clinical detection windows. [29]

Controlled human botanical studies collected and quantified kratom alkaloids in urine for up to 120 hours after dosing. This supports the proposition that targeted urine testing can remain informative for days in some exposure settings, especially for MG and metabolites. It does not establish a universal “five-day window” for every dose, product, metabolizer, or assay. [5]

Plasma / blood

Mitragynine, 7-OH, and several parent botanical alkaloids have been measured with validated LC-MS/MS methods in controlled human studies. The time to last quantifiable concentration varies dramatically by analyte, dose, repeated use, and assay sensitivity. [5-7]

In the 2026 concentrated-mitragynine-extract study, 7-OH remained quantifiable much longer in some high-dose/repeated-dose participants than in low-dose participants, again demonstrating why a single blood “window” is not defensible. [7]

Hair

Mitragynine and 7-OH have been measured in hair using targeted LC-MS/MS forensic methods. Hair can support longer-term exposure assessment, but segment location, hair growth, cosmetic treatment, external contamination, and incorporation kinetics complicate interpretation. Hair testing is unsuitable for determining a precise recent last-use time. [30]

MGM-15

CFSRE has confirmed MGM-15 in toxicology specimens and drug materials using LC-QTOF-MS. No validated population detection window has been published. GC-MS can misidentify the compound because MGM-15 can convert to MG during analysis. [21]

Mitragynine pseudoindoxyl

MP can be measured with targeted modern LC-MS methods and has appeared in commercial/toxicology investigations. No validated blood or urine window exists. Because MP may arise downstream of 7-OH, detection alone may not prove direct MP ingestion. [11-14,18]

MGM-16

No validated clinical biological detection window exists. As of DEA's July 2026 discussion, confirmed real-world consumer/toxicology exposure was not established to the same degree as 7-OH, MP, or MGM-15. [18]

1. A positive 7-OH result does not automatically prove a person swallowed a commercial 7-OH product. Mitragynine is metabolized to 7-OH. Product history and relative analyte concentrations matter. [1-4]
2. A positive MP result does not automatically prove direct MP ingestion. MP can form downstream from 7-OH. [11-14]
3. A negative routine opioid screen does not rule out 7-OH intoxication or withdrawal. Standard immunoassay design is the problem, not necessarily the patient's history. [28,29]
4. Do not infer last-dose timing from a qualitative urine result. Long MG kinetics, metabolite formation, repeated dosing, renal function, assay cutoff, and product composition make back-calculation unreliable. [5-7]
5. Do not use ex-vivo plasma stability as a clinical half-life. The approximately 99-minute 7-OH value from the pseudoindoxyl conversion experiment is a laboratory plasma-incubation observation, not a systemic human PK parameter. [11,12]
6. Do not treat botanical-kratom 7-OH half-life as purified-7-OH PK. Formation from MG can distort the apparent terminal phase. [4-7]
7. Commercial labels are not dependable analytical records. Multiple recent product surveys found large differences between labelled and measured alkaloids, semisynthetic profiles, undeclared active compounds, and oxidation products. [23,31,32]
8. GC-MS can create identification artifacts for some emerging analogues. MGM-15 is a particularly important example because it can transform to MG during GC analysis. [21]
9. “Kratom” is chemically too broad for many clinical conclusions. Botanical leaf, MG-rich extract, purified 7-OH, MP products, MGM-15 products, and mixtures should be documented separately whenever possible.

The most important unresolved questions for the current public-health crisis are:

• Direct human PK of purified high-dose 7-OH, including Cmax, Tmax, oral/sublingual bioavailability, distribution, intrinsic elimination half-life, accumulation with frequent redosing, and active-metabolite contribution.
• The fraction of direct 7-OH converted to MP in vivo in humans.
• Human PK, metabolism, elimination, and toxicity of MGM-15 and MGM-16.
• Reliable biological detection windows for purified 7-OH, MP, MGM-15, MGM-16, and 3DMTG.
• Whether analyte ratios can reliably distinguish botanical kratom use, MG extract use, purified 7-OH use, and direct MP use.
• Quantitative contribution of 9-O-demethylmitragynine to analgesia, intoxication, dependence, or withdrawal in humans.
• Whether serotonergic active metabolites of speciogynine/paynantheine contribute materially to the distinctive affective or sleep features reported during botanical kratom withdrawal.
• How hepatic impairment, renal impairment, CYP3A inhibition/induction, CYP2D6 phenotype, and polysubstance exposure alter direct 7-OH disposition.
• Whether chronic high-frequency 7-OH dosing produces nonlinear kinetics or tissue redistribution that meaningfully changes buprenorphine induction timing.

These gaps should be presented prominently. They are not weaknesses in the resource; they are the current state of the science.

Botanical kratom: Leaf-derived Mitragyna speciosa material containing a mixture of naturally occurring alkaloids, usually dominated by mitragynine.

Mitragynine (MG): Principal kratom alkaloid and metabolic precursor to 7-OH.

7-OH / 7-hydroxymitragynine: Potent opioid-active alkaloid that exists in trace botanical quantities, is formed metabolically from MG, and is now sold in highly concentrated/semi-synthetic products.

Mitragynine pseudoindoxyl (MP): Potent rearrangement product downstream of 7-OH that is also sold directly as a semisynthetic opioid-active compound.

MGM-15: Dihydro-7-OH analogue now documented in commercial drug material and U.S. toxicology specimens; human PK and safety are essentially undefined.

MGM-16: Fluorinated MGM-15/7-OH analogue from medicinal-chemistry research; potent opioid activity in animals, with human PK and safety undefined.

Active metabolite: A metabolite with demonstrated pharmacologic activity, not merely a compound detectable after exposure.

Phase I metabolism: Oxidation, reduction, hydrolysis, or demethylation that changes the parent molecular structure.

Phase II metabolism: Conjugation, commonly glucuronidation or sulfation, usually increasing water solubility and facilitating elimination.

Detection window: The interval during which a specified analyte can be detected above a specified assay cutoff in a specified biological matrix. It is assay- and dose-dependent and should not be treated as a universal property of the drug.

Formation-limited kinetics: A situation in which the measured decline of a metabolite reflects how quickly it is still being produced from a longer-lived precursor, not simply how quickly the metabolite itself is eliminated.

Use these labels directly beside claims when helpful:

• Human controlled data — prospective human pharmacokinetic or interaction study.
• Human confirmed metabolite — directly identified in human plasma, urine, or ex-vivo human biological systems.
• Clinical case evidence — case report or small case series.
• Preclinical functional evidence — receptor/cellular/animal pharmacology.
• Forensic/commercial evidence — confirmed in marketed products, seized material, or toxicology testing.
• Clinical inference — reasonable extrapolation from pharmacology plus direct clinical experience, but not established by controlled study.
• Unknown — no adequate evidence currently available.

This hierarchy is particularly important for withdrawal timelines and buprenorphine timing, where the current literature does not support false precision.

For the professional biography associated with this resource, the public CSAM record independently confirms that Brian Harris, MD served as faculty for the 2025 California Society of Addiction Medicine Addiction Medicine Board Exam Preparation Course and lists his board certifications in Addiction Medicine, Anesthesiology, and Sleep Medicine. [38]

An archived August 2025 Basic Sciences & Addiction - Addiction Medicine Board Review deck identifies Brian Harris, MD as the presenter and contains a dedicated board-style kratom neuropharmacology question and explanation focused on mitragynine's opioid-receptor pharmacology. [41] This is useful contemporaneous evidence that kratom pharmacology was part of Dr. Harris's addiction-medicine teaching before the present 7-OH regulatory crisis.

Searchable text for “7-hydroxymitragynine” was not found in the retrieved copy. The stronger claim that this specific archived deck explicitly covered 7-OH should therefore remain dependent on locating the relevant slide/version rather than being stated as independently verified. The website should describe prior teaching experience without implying that CSAM endorses the present EusomniaMD resource.

1. Kruegel AC, et al. 7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects. ACS Central Science. 2019;5:992-1001. doi:10.1021/acscentsci.9b00141.
2. Kamble SH, et al. Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy. ACS Pharmacology & Translational Science. 2020;3:1063-1068. doi:10.1021/acsptsci.0c00075. PMID:33344889.
3. Basiliere S, Kerrigan S. CYP450-Mediated Metabolism of Mitragynine and Investigation of Metabolites in Human Urine. Journal of Analytical Toxicology. 2020;44:301-313. doi:10.1093/jat/bkz108.
4. Jaisi A, et al. Effects of Itraconazole on Pharmacokinetics of Mitragynine and 7-Hydroxymitragynine in Healthy Volunteers. ACS Pharmacology & Translational Science. 2024;7:823-833. doi:10.1021/acsptsci.3c00335. PMID:38481700.
5. Tanna RS, et al. Clinical Pharmacokinetic Assessment of Kratom (Mitragyna speciosa), a Botanical Product with Opioid-like Effects, in Healthy Adult Participants. Pharmaceutics. 2022;14:620. PMID:35335999.
6. Huestis MA, et al. Human Mitragynine and 7-Hydroxymitragynine Pharmacokinetics after Single and Multiple Daily Doses of Oral Encapsulated Dried Kratom Leaf Powder. Molecules. 2024;29:984.
7. Huestis MA, et al. Mitragynine and 7-hydroxy-mitragynine plasma pharmacokinetics in humans after single and 15 multiple oral kratom extract doses. Journal of Analytical Toxicology. 2026;50(6):bkag042. doi:10.1093/jat/bkag042. PMID:42266029. (Industry relationships disclosed by the authors.)
8. Matsumoto K, et al. Partial agonistic effect of 9-hydroxycorynantheidine on mu-opioid receptor in the guinea-pig ileum. Life Sciences. 2006;78:2265-2271. doi:10.1016/j.lfs.2005.09.030. PMID:16266723.
9. Philipp AA, et al. Classic LC-MS/GC-MS studies of mitragynine phase-I and phase-II metabolites in rat and human urine. Journal of Mass Spectrometry. 2009.
10. Basiliere/Kerrigan and related forensic metabolite studies documenting O-demethylated, carboxylated, glucuronidated, and sulfated MG metabolites in human urine. See ref. 3 and its cited metabolite literature.
11. Kamble SH, et al. Human-plasma ex-vivo conversion of 7-OH to MP. See ref. 2. In pooled human plasma, 53.8 ± 1.6% of incubated 7-OH was converted to MP by 120 min under the experiment's conditions; this is not a systemic human conversion fraction.
12. Zhou Y, et al. Predicted Mode of Binding to and Allosteric Modulation of the Mu-Opioid Receptor by Kratom's Alkaloids with Reported Antinociception In Vivo. Biochemistry. 2021;60:1420-1429. doi:10.1021/acs.biochem.0c00658. PMID:33274929.
13. Crandall WJ, et al. Mixtures Biotransformation: Multilayer Molecular Networking of Kratom Liver Metabolites. Journal of Natural Products. 2026. doi:10.1021/acs.jnatprod.5c01235.
14. Contemporary forensic/commercial analyses of mitragynine pseudoindoxyl and related semisynthetic kratom-opioid products; interpret biological detection with route and product chemistry in mind.
15. Leon F, et al. Activity of Mitragyna speciosa (Kratom) Alkaloids at Serotonin Receptors. Journal of Medicinal Chemistry. 2021;64:13510-13523. doi:10.1021/acs.jmedchem.1c00726.
16. Leon et al. supporting information and metabolic experiments for 9-O-desmethylspeciogynine. See ref. 15.
17. Leon et al. supporting information and metabolic experiments for 9-O-desmethylpaynantheine. See ref. 15.
18. U.S. Drug Enforcement Administration. Schedules of Controlled Substances: Temporary Placement of Mitragynine Pseudoindoxyl, MGM-15, and MGM-16 in Schedule I - Notice of Intent. Federal Register. July 6, 2026; Docket DEA-1644.
19. Gour A, et al. From Kratom to Semi-Synthetic Opioids: The Rise and Risks of MGM-15. Drug Testing and Analysis. 2025;17:2384-2389. doi:10.1002/dta.3952. PMID:40936282.
20. Matsumoto K, et al. Orally active opioid mu/delta dual agonist MGM-16, a derivative of the indole alkaloid mitragynine, exhibits potent antiallodynic effect on neuropathic pain in mice. Journal of Pharmacology and Experimental Therapeutics. 2014;348:383-392. PMID:24345467.
21. Center for Forensic Science Research and Education (CFSRE), NPS Discovery. MGM-15 analytical monograph / public alert. 2025-2026. Use the specific monograph version cited by the website when discussing analytical artifacts.
22. Medicinal-chemistry studies of MGM-15/MGM-16 and fluorinated 7-OH analogues; see ref. 20 and later structure-activity work.
23. Contemporary 2025-2026 market/product analyses of semisynthetic 7-OH-related alkaloids and label-content discrepancies.
24. Bhowmik S, et al. and related medicinal-chemistry studies of hydroxylated/pseudoindoxyl analogues derived from Mitragyna scaffolds.
25. Flores-Bocanegra L, et al. The Chemistry of Kratom [Mitragyna speciosa]: Updated Characterization Data and Methods to Elucidate Indole and Oxindole Alkaloids. Journal of Natural Products. 2020.
26. Manwill PK, et al. Modern LC-MS/NMR characterization of kratom alkaloid chemotypes and minor constituents. 2022.
27. Chakraborty S, et al. Kratom Alkaloids as Probes for Opioid Receptor Function: Pharmacological Characterization of Minor Indole and Oxindole Alkaloids from Kratom. ACS Chemical Neuroscience. 2021;12:2661-2678. doi:10.1021/acschemneuro.1c00149. PMID:34213886.
28. Dedicated mitragynine immunoassays have been developed, but they are not equivalent to routine hospital opiate screens and require assay-specific interpretation/cross-reactivity review.
29. Targeted urine methods for MG/7-OH include validated LC-MS/MS and later CZE-MS/MS approaches. A 2015 LC-MS/MS method demonstrated sub-ng/mL analytical sensitivity; analytical LOD is not the same as a clinical cutoff or detection window.
30. 2024 Journal of Analytical Toxicology LC-MS/MS hair method for mitragynine and 7-OH; hair establishes historical exposure, not acute timing.
31. Brown et al. 2026 Journal of AOAC International analysis of high-7-OH products showing alkaloid concentrations/profiles inconsistent with authentic botanical leaf.
32. 2026 quantitative commercial-product analyses documenting label disagreement, oxidation products, and semisynthetic chemical signatures.
33. An in vitro evaluation on metabolism of mitragynine to 9-O-demethylmitragynine. Human liver S9 study reporting 9ODM formation as a major MG pathway and supporting CYP3A contribution. 2024.
34. Chakraborty S, et al. Oxidative Metabolism as a Modulator of Kratom's Biological Actions. Journal of Medicinal Chemistry. 2021;64:16553-16572. doi:10.1021/acs.jmedchem.1c01111. Establishes preclinical formation/activity of 7-OH, MP, and 3DM, including non-CYP 3DM formation.
35. Avula B, et al. Quantitative analysis of 7-hydroxymitragynine in commercial kratom products and its stability under chemical and physiological conditions. Phytochemistry. 2026. PMID:41825819. Reports degradation of 7-OH to 3DM under simulated gastric conditions; treat this as product/GI chemistry until human in-vivo conversion is quantified.
36. Gour A, et al. Mislabeling and Status of Semisynthetic Kratom-Derived Products in the US Market. Drug Testing and Analysis. 2026. doi:10.1002/dta.70122. PMID:42448619. Reports frequent label-content disagreement and pharmacologically/toxicologically relevant compounds including 7-OH and 3DM.
37. Metabolic literature identifying 9-O-demethylmitragynine glucuronide (9-hydroxycorynantheidine glucuronide) and reporting weak MOR affinity; clinical activity is unproven. See refs. 9, 13 and cited pharmacology therein.
38. California Society of Addiction Medicine. 2025 Addiction Medicine Board Exam Preparation Course. Official CSAM Education Center faculty listing: Brian Harris, MD.
39. Reissig CJ, et al. A Pilot, Dose-Finding, Pharmacodynamic and Pharmacokinetic Study of Orally Administered Botanical Kratom. J Clin Psychopharmacol. 2026;46:386-398. doi:10.1097/JCP.0000000000002158. PMID:41837407.
40. Gour A, et al. Drug Testing and Analysis 2026 commercial-product study; see ref. 36.
41. Harris B. Basic Sciences & Addiction - Addiction Medicine Board Review. August 2025 archived presentation deck. Contains a board-style kratom pharmacology item discussing mitragynine as a partial mu-opioid agonist and kappa-opioid antagonist. Internal source archive; distinguish this from formal CSAM endorsement.

For the public-facing resource, prefer wording such as:

rather than:

Likewise, prefer:

rather than assigning a single half-life to the commercial drug.

The scientifically useful message is not that every number is known. It is that we now know enough to identify the pharmacologically important pathway, and we know exactly where the evidence stops.