Metabolites, kinetics & testing
A clinician-facing overview of what a kratom or 7-OH exposure becomes in the body, what targeted testing can establish, and the limits that should shape every result and treatment decision.
Start with the limits of the available pharmacokinetics
Most controlled human pharmacokinetic data come from botanical kratom, dried leaf, tea, or mitragynine-rich extract. In those studies, 7-OH is measured partly as a metabolite still being formed from mitragynine; they do not reproduce repeated direct ingestion of purified or semisynthetic commercial 7-OH. E20E21
Data insufficient The clinically relevant human bioavailability, accumulation pattern, receptor exposure, intrinsic elimination half-life, and withdrawal relationship after repeated high-dose direct 7-OH ingestion remain unknown. A terminal half-life measured after botanical exposure must not be pasted onto a bottle of purified 7-OH or used as a countdown clock for buprenorphine.
“Detected in urine” does not mean “primarily eliminated unchanged in urine,” and neither statement establishes a fixed clinical detection window. A urine result reflects the selected analyte, assay, cutoff, specimen timing, exposure pattern, metabolism, hydration, renal function, and specimen handling.
A plasma half-life is not duration of receptor occupancy, intoxication, withdrawal risk, or urine positivity. Formation from a longer-lived parent can make a measured metabolite terminal phase formation-limited rather than a direct measure of intrinsic elimination.
The metabolic map
Established The central pharmacologically important chain is mitragynine to 7-OH to mitragynine pseudoindoxyl (MP). CYP3A4 is the principal established enzyme for mitragynine-to-7-OH conversion; a controlled healthy-volunteer interaction study found that CYP3A inhibition reduced 7-OH formation after botanical exposure. E16E19
That pathway does not make CYP3A inhibition clinically simple. Inhibition may reduce formation of 7-OH from mitragynine while reducing clearance of mitragynine, directly ingested 7-OH, or other compounds. The net effect depends on what the patient actually took and when.
BOTANICAL KRATOM / MITRAGYNINE EXPOSURE
Mitragynine (MG)
|
|-- CYP3A4 --> 7-hydroxymitragynine (7-OH; 7-HMG)
| |
| |-- rearrangement in human plasma ex vivo and liver-associated systems -->
| | mitragynine pseudoindoxyl (MP)
| |
| '-- chemical degradation can yield 3-dehydromitragynine (3DM)
| under simulated gastric conditions; clinical in-vivo importance unknown
|
|-- non-CYP, NADPH-independent oxidation demonstrated in human liver fractions -->
| 3-dehydromitragynine (3DM; active/toxic in preclinical systems)
|
|-- CYP2C19 + CYP2D6 + CYP3A4 --> 9-O-demethylmitragynine
| (= 9-hydroxycorynantheidine; 9OH)
| |
| '-- phase II --> 9OH glucuronide (9G) and sulfate conjugates
|
|-- CYP2D6 + CYP2C19 + CYP2C18 --> 16-carboxymitragynine
|
|-- CYP2C19 --> 9-O-demethyl-16-carboxymitragynine
|
'-- additional O-demethylation, ester hydrolysis, oxidation/reduction,
and conjugation --> glucuronide/sulfate metabolites --> urine
Speciogynine
'-- O-demethylation --> 9-O-desmethylspeciogynine
(5-HT1A agonist in functional assays)
Paynantheine
'-- O-demethylation --> 9-O-desmethylpaynantheine
(5-HT1A agonist in functional assays)
Emerging Conversion of 7-OH to MP is demonstrated in human plasma ex vivo and related systems. MP is pharmacologically active and may also be manufactured and taken directly; the fraction formed in living humans and its contribution after commercial 7-OH use are not established. E18
Core compounds and clinically important metabolites
For clinical interpretation, separate a botanical parent alkaloid, a biologically formed metabolite, and a deliberately modified analogue. A compound may be detectable without being active, and an active compound may not be on a routine laboratory panel.
| Compound | Category | What is established | Clinical interpretation |
|---|---|---|---|
| Mitragynine (MG) | Major botanical parent alkaloid | Metabolic precursor to 7-OH and multiple other metabolites. | Botanical exposure is not a single-compound exposure; MG can produce a long metabolic tail. E16E20 |
| 7-hydroxymitragynine (7-OH) | Trace botanical alkaloid; active MG metabolite; commercial semisynthetic drug | Formed through CYP3A-mediated oxidation of MG and measured after botanical exposure. | A positive result may reflect metabolic formation, direct 7-OH exposure, or both. E16E19 |
| 9-O-demethylmitragynine (9OH) | Active MG metabolite | Partial μ-opioid receptor agonist and prominent phase-I urinary metabolite; CYP2C19, CYP2D6, and CYP3A4 are implicated. | Useful targeted exposure marker; human plasma half-life and validated detection window are not established. E17 |
| Mitragynine pseudoindoxyl (MP) | Active downstream product; semisynthetic commercial compound | Ex-vivo human plasma conversion from 7-OH is demonstrated. | Detection does not, by itself, distinguish direct MP use from downstream formation. E18 |
| 3-dehydromitragynine (3DM) | Oxidative MG product; degradation/product constituent | Can form through a non-CYP oxidative pathway and may arise through chemical degradation or processing. | Preclinical activity and toxicity signals do not establish the human in-vivo contribution. E10 |
| 9-O-desmethylspeciogynine and 9-O-desmethylpaynantheine | Active botanical-metabolite pathways | Both activate 5-HT1A receptors in functional assays. | Human concentration-time profiles and clinical contribution are unknown; this is not evidence that purified 7-OH is serotonergic. E13 |
Native alkaloids with measured human pharmacokinetics
Established Controlled botanical studies demonstrate oral mitragynine absorption, a long terminal phase, and accumulation with repeated exposure. The values below are orientation numbers from botanical context, not pharmacokinetics of a purified 7-OH tablet. E20E21
| Alkaloid | Median terminal half-life | Meaning for interpretation |
|---|---|---|
| Mitragynine | 45.3 h | Major parent alkaloid with a long terminal phase. |
| Speciogynine | 23.5 h | Parent botanical alkaloid; its O-demethylated metabolite has functional serotonergic activity in vitro. |
| Paynantheine | 27.0 h | Parent botanical alkaloid; likewise has an O-demethylated serotonergic metabolite. |
| Speciociliatine | 12.3 h | Botanical alkaloid with measured human PK after botanical exposure. |
| Mitraciliatine | 17.8 h | Botanical alkaloid with measured human PK after botanical exposure. |
| Isopaynantheine | 14.4 h | Botanical alkaloid with measured human PK after botanical exposure. |
| 7-OH | 5.67 h | Measured in a low-dose botanical tea context, where 7-OH was substantially metabolically generated. It is not direct high-dose 7-OH PK. |
In a controlled tea study, 7-OH had a median terminal half-life of about 5.67 hours; repeated dried-leaf and extract studies produced regimen-dependent, sometimes longer estimates. These values describe botanical or mitragynine-rich exposure, not intrinsic elimination after direct high-dose 7-OH. E20E21
Semisynthetic derivatives change the exposure question
MP, MGM-15, MGM-16, and 3DM must not be collapsed into “kratom.” They differ in origin, available human evidence, and analytical requirements. Product surveys have documented semisynthetic chemistry, label-content disagreement, and oxidation products in material sold as kratom or 7-OH. E10
| Compound | Relationship | Testing and human evidence |
|---|---|---|
| Mitragynine pseudoindoxyl (MP) | Downstream 7-OH rearrangement product and directly manufactured compound. | Targeted modern mass spectrometry can identify it; no validated human systemic half-life or clinical window. E18 |
| MGM-15 | Semisynthetic dihydro-7-OH analogue, not a metabolite. | Commercial material and toxicology specimens have been reported, but controlled human PK, metabolism, safety, and withdrawal data are absent. E39 |
| MGM-16 | Fluorinated dihydro-7-OH analogue. | Human pharmacokinetics, metabolism, and a validated biological window are unknown; targeted high-resolution testing needs an appropriate standard. |
| 3DM | Oxidative MG product and possible 7-OH degradation/product constituent. | Targeted high-resolution testing is possible in appropriate methods, but clinical human PK and biological detection timing remain unknown. E10 |
Elimination is predominantly metabolic, not intact renal clearance
Kratom alkaloids undergo extensive Phase I and Phase II metabolism. Urine can contain parent alkaloids, O-demethylated and carboxylated metabolites, and glucuronide or sulfate conjugates. The presence of a compound in urine therefore does not show that unchanged renal excretion is its primary route of elimination.
Controlled botanical work found low unchanged urinary recovery for mitragynine relative to administered amount, while some minor alkaloids showed higher intact renal recovery. Complete human mass-balance, biliary-clearance, and fecal-recovery studies remain limited; no human mass-balance study has established disposition after direct high-dose purified 7-OH.
Renal dysfunction may alter metabolite handling and hepatic dysfunction may alter formation or clearance, but there is no validated dose-adjustment model for purified 7-OH. Product identity, co-medications, and clinical status remain more informative than a universal adjustment rule.
Toxicology testing: what to order and how to read it
Routine opiate immunoassays are designed around morphine-like structures. They do not specifically identify mitragynine, 7-OH, MP, MGM-15, or MGM-16. A negative routine screen is an assay limitation, not a reason to dismiss a compatible history, intoxication, or withdrawal syndrome.
When the result will change management, order a targeted chromatography-mass-spectrometry method and name the clinical question. LC-MS/MS, LC-HRMS, LC-QTOF, and related methods can detect selected parent alkaloids, metabolites, and analogues when standards, transitions, chromatographic separation, and validation are appropriate. E17E37E38
- For a prior-exposure question: request urine LC-MS/MS or LC-HRMS that explicitly includes mitragynine, 7-OH, 9-O-demethylmitragynine, and 16-carboxymitragynine; add MP, 3DM, MGM-15, and MGM-16 where a concentrated modern product is suspected and the laboratory can validate them.
- For recent exposure, intoxication, or quantitative interpretation: request blood or plasma LC-MS/MS with the named analytes. A measured concentration confirms the selected analyte in the selected matrix; it does not independently establish impairment, dose, or readiness for a medication transition.
- For product attribution: retain and arrange analysis of the actual tablet, strip, shot, or powder when feasible. Biological results alone may not distinguish botanical exposure, direct 7-OH use, or direct MP use.
- For historical exposure: hair LC-MS/MS may support a longer-term exposure assessment, but it cannot provide a precise recent last-use time.
Record last reported use, collection time, product identity, all co-ingestants, matrix, analyte list, cutoff or reporting limit, whether conjugates were measured directly or after hydrolysis, and specimen handling. Targeted methods can be highly useful, but analytical sensitivity is not a clinical detection window. E37E38
Interpretive guardrails
- A positive 7-OH result does not prove direct ingestion of a 7-OH product because mitragynine can form 7-OH metabolically. E16E19
- A positive MP result does not prove direct MP ingestion because downstream formation is possible. E18
- Do not infer last-dose timing from a qualitative urine result. No validated clinical urine window exists for direct purified 7-OH, MP, MGM-15, MGM-16, or 3DM. E20E21
- GC-based analysis can create an MGM-15-to-mitragynine identification artifact; discuss unexpected or high-stakes results with the laboratory director. E39
What remains genuinely unknown
Data insufficient There is no controlled human pharmacokinetic study of direct high-dose purified 7-OH. The evidence does not establish its tablet or sublingual bioavailability, intrinsic elimination half-life, accumulation during frequent redosing, receptor-occupancy duration, or validated matrix-specific detection window.
Also unresolved are the in-vivo fraction of 7-OH converted to MP; human PK, metabolism, elimination, and toxicity for MGM-15 and MGM-16; a ratio that reliably distinguishes botanical kratom, MG extract, purified 7-OH, and direct MP exposure; and how organ impairment, CYP3A modulation, CYP2D6 phenotype, and polysubstance exposure alter direct 7-OH disposition.
These are not gaps to conceal. They explain why a symptom-led clinical assessment and transparent laboratory interpretation are safer than a fixed interval, a presumed dose, or a qualitative result treated as a clock.
Need the complete compound, pathway, and detection reference?
The chemistry and detection reference preserves the complete glossary, compound categories, analytical matrix, internal source list, and all stated uncertainties.
This module is educational and is not medical advice. It does not create a physician—patient relationship or replace an individual assessment. Patients who may be dependent on 7-OH or kratom alkaloids should seek an addiction medicine professional; use the buprenorphine prescriber finder to locate treatment support.