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Master glossary
Metabolite = formed biologically from another kratom alkaloid. Botanical alkaloid = present in M. speciosa. Semisynthetic analogue = deliberately modified from a kratom scaffold. Several compounds occupy more than one category.
| Compound | Also called | Category | Why it matters clinically | Human detection / timing status |
|---|---|---|---|---|
| Mitragynine | MG, MTG | Major botanical parent alkaloid | Main botanical exposure; precursor to multiple active metabolites, especially 7-OH | Plasma/urine/hair measurable by targeted MS. Botanical human t½ commonly ~40–70 h depending regimen; unchanged urinary recovery very low. |
| 7-hydroxymitragynine | 7-OH, 7-HMG, 7-OH-MTG | Trace botanical alkaloid; active human MG metabolite; semisynthetic retail drug | Potent opioid-active compound driving high-concentration products | Targeted assays exist. After 2-g botanical tea, median terminal t½ ~5.67 h; urine informative through 120-h collection in that study. Direct purified high-dose human PK is unknown. |
| 9-O-demethylmitragynine | 9ODM, 9OH, 9-hydroxycorynantheidine | Active MG metabolite | MOR partial agonist; prominent phase-I urinary metabolite | Identified in human urine by targeted MS; plasma PK and validated urine window unknown. |
| Mitragynine pseudoindoxyl | MP | Active downstream 7-OH/MG product; manufactured semisynthetic drug | Potent opioid-active rearrangement product; may be ingested directly or form downstream from 7-OH | Targeted LC-HRMS/LC-QTOF can identify it. No validated systemic half-life or clinical window; detection alone does not prove direct ingestion. |
| 3-dehydromitragynine | 3DM, 3DMTG | Oxidative MG product; degradation/product constituent | Preclinical MOR partial agonism plus high-dose non-opioid toxicity signal; found in modern commercial products | Targeted HRMS can identify it in research/product matrices; human in-vivo PK unknown. |
| 9-O-demethylmitragynine glucuronide | 9G | Phase-II 9OH conjugate | Weak MOR affinity reported; clinically meaningful agonism not established | Conjugate-aware HRMS or hydrolysis methods; timing unknown. |
| 16-carboxymitragynine | 16-COOH-MG | MG metabolite / hydrolysis product | Useful urinary/product marker; pharmacologic activity not established | Identified in human urine by targeted MS; no validated window. |
| 9-O-demethyl-16-carboxymitragynine | 9ODM-16-COOH-MG | MG metabolite | Pathway marker; CYP2C19 prominent in recombinant studies | Human urine identification reported; no validated window. |
| 9-O-desmethylspeciogynine | — | Active speciogynine metabolite | Functional 5-HT1A agonist in vitro (botanical pathway) | Targeted metabolomics possible; clinical window unknown. |
| 9-O-desmethylpaynantheine | — | Active paynantheine metabolite | Functional 5-HT1A agonist in vitro | Targeted MS possible; clinical window unknown. |
| MGM-15 | dihydro-7-OH, DH7OH | Semisynthetic 7-OH analogue, not a metabolite | Higher hMOR/hDOR binding affinity than 7-OH in published in-vitro work; commercial exposure documented | LC-MS identification feasible. No validated human half-life or biological window. |
| MGM-16 | 9-fluoro-dihydro-7-hydroxymitragynine | Synthetic/semisynthetic analogue, not a metabolite | Potent preclinical mu/delta agonist; adjacent to MGM-15 in analogue market/regulatory response | No established clinical human PK or validated window. |
| Minor botanical alkaloids | speciogynine, paynantheine, speciociliatine, mitraciliatine, isopaynantheine, others | Botanical parents / minor alkaloids | Contribute to botanical polypharmacology; not principal drivers of purified 7-OH dependence alone | Several have controlled human plasma PK after botanical exposure; compound-specific clinical urine windows not validated. |
Not shown as established human metabolites: medicinal-chemistry probes such as 7-hydroxypaynantheine, 7-hydroxyspeciogynine, paynantheine pseudoindoxyl, and speciogynine pseudoindoxyl without direct metabolic evidence.
Active metabolites with the strongest evidence
| Compound | Parent / pathway | Pharmacology | Human metabolic evidence | Human half-life | Detectability |
|---|---|---|---|---|---|
| 7-OH | MG via predominantly CYP3A4 oxidation; also trace botanical / processing product | Potent MOR agonist; efficacy assay-dependent | High after botanical/MG-rich exposure; CYP3A interaction study supports formation in vivo | Direct purified 7-OH: unknown. Botanical tea median terminal t½ ~5.67 h (formation-limited context) | Targeted LC-MS/MS / HRMS. One 2-g tea study: plasma ~24 h; urine through 120-h collection—not a universal five-day window |
| 9OH / 9ODM | MG O-demethylation (CYP2C19 / 3A4 / 2D6 implicated) | MOR partial agonist | Moderate–high; major phase-I urinary metabolite in kratom-user work | Unknown in humans | Targeted metabolite MS in urine; no validated time-since-last-use window |
| MP | Downstream of MG/7-OH; also manufactured directly | Potent opioid-active; strong MOR activity with DOR/KOR antagonism in several assays | Moderate; human plasma ex vivo formation demonstrated; in-vivo fraction unknown | Systemic human half-life unknown (ex-vivo plasma instability ≠ systemic PK) | Targeted LC-HRMS/QTOF; positive result may reflect direct exposure, metabolism, or both |
| 3DM | Non-CYP oxidative pathway in human liver fractions; also gastric degradation product of 7-OH in chemistry work | Preclinical MOR partial agonism; high-dose non-opioid toxicity signal in mice | Limited for circulating in-vivo human metabolite status | Unknown in humans | Targeted HRMS in products/research matrices; no validated clinical window |
| 9-O-desmethylspeciogynine / paynantheine | O-demethylation of minor botanical alkaloids | Functional 5-HT1A agonists in vitro | Moderate pharmacology; limited human exposure data | Unknown | Targeted MS possible; no routine clinical window |
| 9G | Glucuronidation of 9OH | Weak MOR affinity only; not proven clinically active opioid | Phase-II formation supported; quantitative in-vivo exposure poorly defined | Unknown | Conjugate-aware methods; no validated window |
Bottom line: best-established clinically relevant chain is MG → 7-OH → MP. Secondary pathway MG → 9OH → 9G. 3DM is pharmacologically and toxicologically interesting preclinically; human contribution remains unknown.
Controlled human PK orientation (botanical context)
Useful orientation numbers—not direct-purified-7-OH pharmacokinetics. Median terminal half-lives after a controlled single-dose standardized kratom product in healthy adults:
| Alkaloid | Median terminal half-life | Comment |
|---|---|---|
| Mitragynine | 45.3 h | Major parent; long terminal phase |
| Speciogynine | 23.5 h | Parent botanical alkaloid |
| Paynantheine | 27.0 h | Parent botanical alkaloid |
| Speciociliatine | 12.3 h | Parent botanical alkaloid |
| Mitraciliatine | 17.8 h | Parent botanical alkaloid |
| Isopaynantheine | 14.4 h | Parent botanical alkaloid |
| 7-OH | 5.67 h | Mostly metabolically generated in this botanical-exposure context |
A separate dried-leaf study found mean MG half-lives around ~43 h (single) and ~68 h (repeated), while mean 7-OH estimates were roughly ~5 h (single) and ~25 h (repeated). Concentrated-mitragynine-extract work reports highly variable 7-OH terminal estimates with possible saturation—another reason not to use a single fixed 7-OH half-life clinically.
Renal elimination: unchanged mitragynine recovery in urine is minimal; metabolism and conjugation dominate disposition for several alkaloids.
Other identified mitragynine metabolites
Important for forensic interpretation; clinically meaningful pharmacologic activity has not been established for each:
- 16-carboxymitragynine
- 9-O-demethyl-16-carboxymitragynine
- 17-O-demethyl-16,17-dihydromitragynine
- 9,17-O-bisdemethyl-16,17-dihydromitragynine
- 17-carboxy-16,17-dihydromitragynine
- 9-O-demethyl-17-carboxy-16,17-dihydromitragynine
- Glucuronide and sulfate conjugates of O-demethylated/carboxylated metabolites
Related pages
Chemistry summary · Pharmacology · Appendix A (full Markdown) · Combined chemistry reference · Full longform resource · Evidence library