This page shows what was measured, who it was measured in, and what that does not settle.
What Mitragynine does in the body
Nothing approved. It is sold in petrol stations and smoke shops, is used by around two million American adults a year, and works partly through the same receptor as morphine
Kratom leaf contains mitragynine, which on its own binds the µ-opioid receptor weakly and in a laboratory assay actually blocked it rather than switching it on. The liver then converts some of it into 7-hydroxymitragynine, which does switch the receptor on. So the leaf is a slow, self-limiting delivery system for a metabolite — and the concentrated 7-hydroxymitragynine products now on sale skip the leaf and the liver entirely, delivering the active compound directly at doses the plant could never produce. That is the whole difference between the traditional material and the current retail market.
What happened in people
Mitragynine behaved as an antagonist and 7-hydroxymitragynine as a partial agonist (Emax 41.3%) at the human µ-opioid receptor in the same [35S]GTPγS assay
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
That kratom is an opioid in the simple sense — the parent alkaloid is not a µ agonist in functional assay; the metabolite is
Where it acts
µ-opioid receptors in the central nervous system and gut, reached after CYP3A4 in the liver converts mitragynine into the metabolite that actually does the work
Kind of result
The kind of result is not recorded
Supervision
Not usually supervised: sold as a supplement or food ingredient where recorded. That is a legal category, not a safety judgement.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · EP479K822J · read 2026-08-29
The organism is Mitragyna speciosa, a species. It is also called kratom.
NCBI Taxonomy · 170351 · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 151 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
µ-opioid receptor affinity and [35S]GTPγS efficacy for mitragynine and 7-hydroxymitragynine, with drug discrimination and antinociception in rats
✓ The study showed what it set out to show
Who was studied
Obeng et al. 2021 receptor and behavioural pharmacology (University of Florida)
How many people
0
Study design
Preclinical in vitro and rat in vivo
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Mitragynine an antagonist in [35S]GTPγS; 7-hydroxymitragynine a partial agonist, Emax 41.3%. Morphine-lever substitution 72.3% for mitragynine, 99.7% for 7-hydroxymitragynine
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The Ki values in the abstract are presented in the order opposite to the paper's own significance statement, and a correction was published in 2022. No human data.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral leaf powder, capsules and extracts; increasingly sublingual tablets and films of the isolated metabolite
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Overdose deaths with kratom detected on postmortem toxicology, and those with kratom determined to be a cause of death
✓ The study showed what it set out to show
Who was studied
CDC SUDORS analysis, 27 states, July 2016-December 2017
How many people
27338
Study design
Surveillance analysis of medical-examiner and coroner records
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
152 of 27,338 (0.56%) kratom-positive; kratom a cause of death in 91 of 152 (59.9%), sole substance detected in 7
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Postmortem toxicology protocols were undocumented and varied between and within states, so the number tested for kratom is unknown and the 0.56% is not an exposure rate. Fentanyl was a listed cause in 65.1% of kratom-positive decedents.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral leaf powder, capsules and extracts; increasingly sublingual tablets and films of the isolated metabolite
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Past-year and lifetime prevalence of kratom use in US adults
✓ The study showed what it set out to show
Who was studied
Schimmel et al. 2021 NMURx prevalence survey
How many people
59714
Study design
Cross-sectional weighted survey
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Past-year 0.8% (95% CI 0.7-0.9), about 2,031,803 adults; lifetime 1.3% (95% CI 1.2-1.4), about 3,353,624 adults
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. A non-probability online panel weighted to the adult population, not a household probability sample. Self-report only, with no biological confirmation.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Oral leaf powder, capsules and extracts; increasingly sublingual tablets and films of the isolated metabolite
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Mitragynine
What a person takes: Oral leaf powder, capsules and extracts; increasingly sublingual tablets and films of the isolated metabolite.
The measurement behind this step
Traditional preparation is chewed fresh leaf or a brewed decoction, which delivers mitragynine slowly and is self-limiting through nausea. The current US retail market is dominated by powders, capsules, gummies and — in the DEA product survey — chewable and sublingual tablets designed for rapid absorption, which deliver 7-hydroxymitragynine directly and bypass the metabolic step the plant relies on.
Getting in
Taken as leaf, extract, or a concentrated tablet
Traditionally the leaf is chewed or brewed. The current retail market is powders, capsules, gummies and sublingual films, and some of those contain the active metabolite directly.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Oral leaf powder or extract, delivering mitragynine with trace 7-hydroxymitragynine. Products surveyed by DEA in 2024-2025 carried 1 mg to 700 mg of 7-hydroxymitragynine per serving, most commonly as chewable or sublingual tablets, which bypasses first-pass metabolism entirely.
The liver turns mitragynine into the active compound
Cytochrome enzymes, chiefly CYP3A4, oxidise mitragynine into 7-hydroxymitragynine. This is a metabolic activation, the same pattern as codeine becoming morphine.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
CYP3A4-dominated oxidation of mitragynine yields 7-hydroxymitragynine among other metabolites. Kratom alkaloids also inhibit several P450 isoforms in vitro, so the conversion rate varies with co-medication as well as with genotype.
The parent alkaloid binds the receptor without switching it on. The metabolite switches it partly on — enough for analgesia, euphoria and respiratory depression.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Partial agonism at µ with Emax 41.3% in [35S]GTPγS, against mitragynine's antagonist behaviour in the same assay. In rats 7-hydroxymitragynine fully substituted for morphine in drug discrimination and produced antinociception; mitragynine did neither reliably. Naltrexone reverses both.
At low doses people describe kratom as stimulating rather than sedating, which the opioid receptor does not explain.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Mitragynine carries additional activity at adrenergic and serotonergic targets, and naltrexone failed to reverse its rate-decreasing effects in rats while reversing its discriminative-stimulus effects — direct evidence that part of its in-vivo action is not opioid-mediated.
Dependence, withdrawal and, in the case series, death
Regular use produces opioid-type dependence and withdrawal. In postmortem casework kratom is usually one of several substances, and in a minority of cases it was the only one found.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Kratom was a listed cause of death in 91 of 152 kratom-positive overdose deaths across 27 states, with any fentanyl also listed in 56.0% of those and kratom the sole detected substance in seven. DEA TOX reports 55 fatal and 30 non-fatal 7-hydroxymitragynine cases since 2019 at an average concentration of 463.23 ng/mL.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
An estimated 0.8% of US adults in the past year — about two million people — with users younger than average, 61% male, and over-represented among students and health-care workers.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Where the result stopped carrying
DEA's 2016 attempt to place mitragynine and 7-hydroxymitragynine in Schedule I was withdrawn six weeks after it was announced
No randomised controlled trial of kratom or mitragynine has been completed for pain, for opioid withdrawal, or for anything else
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Varies by country
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Oral leaf powder, capsules and extracts; increasingly sublingual tablets and films of the isolated metabolite
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Not usually supervised: sold as a supplement or food ingredient where recorded. That is a legal category, not a safety judgement.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
The identity record classes it as a botanical or organism preparation; no register records an approval.
No source is stored against this line.
What is in the pack
Traditional preparation is chewed fresh leaf or a brewed decoction, which delivers mitragynine slowly and is self-limiting through nausea.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: The current US retail market is dominated by powders, capsules, gummies and — in the DEA product survey — chewable and sublingual tablets designed for rapid absorption, which deliver 7-hydroxymitragynine directly and bypass the metabolic step the plant relies on.
No source is stored against this line.
Where it is registered
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No register entry is recorded.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Regular use produces opioid-type physical dependence with a withdrawal syndrome, and case reports document dependence severe enough to require inpatient medically managed withdrawal. Acute risks are those of a µ-opioid partial agonist: sedation, respiratory depression and, in reported cases, cardiopulmonary arrest reversed by naloxone. Hepatotoxicity with a cholestatic pattern is reported. In postmortem casework kratom is usually one of several substances, with fentanyl the commonest co-detection. Because the opioid effect depends on CYP-mediated conversion of mitragynine, exposure varies with hepatic enzyme activity and co-medication. Concentrated 7-hydroxymitragynine products remove that variability by delivering the active compound directly, at doses reported up to 700 mg.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Oral leaf powder, capsules and extracts; increasingly sublingual tablets and films of the isolated metabolite
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: The current US retail market is dominated by powders, capsules, gummies and — in the DEA product survey — chewable and sublingual tablets designed for rapid absorption, which deliver 7-hydroxymitragynine directly and bypass the metabolic step the plant relies on.
No source is stored against this line.
What is recorded as being sold
107111 marketed supplement labels list this ingredient, classed as botanical and non-nutrient/non-botanical.
Those labels carry all other and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
Watching one thing carefully can tell you whether it moved. It cannot tell you what moved it.
This is sold without a prescription, so a person can sensibly watch one thing and see whether it moves.
Pick one goal. One goal only. Two at once cannot be told apart afterwards.
Pick one thing to watch. No registered study lists a measure RNAWiki could read for this.
Measure before you start. Take the same measurement several times first. One reading is not a starting point.
Know the swing. Write down how much it moves on its own across a normal week.
Change one thing. Change nothing else at the same time, including training and sleep.
Give it the study length. No finished study window is recorded, so no length is suggested here.
Track whether you took it. Missed days are the most common reason a home test shows nothing.
Read the trend. Look at the line across weeks. A single reading tells you almost nothing.
What not to measure
Anything that swings more day to day than the change you are looking for.
A wearable estimate of sleep stages, which is an estimate and not a measurement.
Weight on one morning, which mostly records water.
A feeling you did not write down before starting.
When to stop
Stop if something new and unpleasant starts, and ask a pharmacist or doctor.
Stop if you cannot keep everything else steady, because the result will not mean anything.
Stop at the end of the window you set, and read the trend then.
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki does not work out an amount for anyone.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That kratom is an opioid in the simple sense — the parent alkaloid is not a µ agonist in functional assay; the metabolite is
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the traditional leaf safety record describes concentrated 7-hydroxymitragynine products, or that the postmortem series describes leaf
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That 91 kratom-involved deaths represent a rate; the number of people tested for kratom, and the number exposed, are both unknown
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That kratom treats opioid withdrawal — it is widely used for that and no controlled trial has tested it
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Mitragynine are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
Mitragynine is not the opioid — the metabolite is
In plain words
In a laboratory assay of receptor activation, mitragynine blocked the µ-opioid receptor rather than switching it on. Its liver metabolite switched it on. In rats, only the metabolite produced pain relief.
What was measured
[35S]GTPγS efficacy at the µ-opioid receptor, drug-discrimination substitution and antinociception in rats, for parent and metabolite separately
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Obeng et al. compared mitragynine and 7-hydroxymitragynine at the human µ-opioid receptor. In [35S]GTPγS stimulation, mitragynine was an antagonist while 7-hydroxymitragynine was a partial agonist with Emax 41.3%. In rats trained to discriminate morphine, mitragynine produced a maximum of 72.3% morphine-lever responding and 7-hydroxymitragynine 99.7%; 7-hydroxymitragynine produced antinociception and mitragynine did not. Naltrexone antagonised all the effects of morphine and 7-hydroxymitragynine, and antagonised the discriminative-stimulus effects of mitragynine but not its rate-decreasing effects. On affinity, the paper's significance statement records 7-hydroxymitragynine as having roughly 9-fold higher µ-opioid affinity than mitragynine; the two Ki values quoted in the abstract, 77.9 and 709 nM, are presented in the order opposite to that statement, and a correction was published in J Pharmacol Exp Ther 2022;383:250. This record therefore reports the direction of the difference and the functional results, which are unambiguous, and assigns no Ki value to either compound.
Written into the record, not signed off as a reviewed claim
CDC: 152 overdose deaths with kratom detected, 91 with kratom as a cause
In plain words
Across 27 states over eighteen months, kratom showed up in the toxicology of 152 of 27,338 overdose deaths. A medical examiner named it as a cause in 91 of those — and in 65% of them fentanyl was also a listed cause.
What was measured
Kratom-positive and kratom-involved overdose deaths with co-detected substances, 27 states, July 2016-December 2017
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
CDC analysed the State Unintentional Drug Overdose Reporting System for July 2016 to December 2017: 27,338 overdose deaths were entered, and 152 (0.56%) tested positive for kratom on postmortem toxicology. A medical examiner or coroner determined kratom to be a cause of death in 91 of the 152 (59.9%), including seven for whom kratom was the only substance detected — though the report notes additional substances cannot be ruled out. Fentanyl and its analogues were the most frequent co-occurring substances: any fentanyl was a listed cause of death for 65.1% of kratom-positive and 56.0% of kratom-involved decedents. Heroin followed at 32.9%, benzodiazepines 22.4%, prescription opioids 19.7% and cocaine 18.4%. About 80% had a documented history of substance misuse and about 90% had no evidence of medically supervised pain treatment. Testing protocols were not documented and varied between and within states, so the denominator for kratom testing is not the full 27,338.
Written into the record, not signed off as a reviewed claim
DEA moved to ban it in 2016, withdrew six weeks later, and is back in 2026
In plain words
In August 2016 the DEA announced it would place kratom's two main alkaloids in Schedule I. In October 2016 it withdrew the notice — an almost unheard-of reversal. In July 2026 it issued a new notice aimed only at concentrated 7-hydroxymitragynine.
What was measured
Sequence and scope of federal scheduling actions on mitragynine and 7-hydroxymitragynine
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
DEA published a notice of intent to temporarily place mitragynine and 7-hydroxymitragynine into Schedule I on 31 August 2016 (81 FR 59929), then published a withdrawal of that notice on 13 October 2016 (81 FR 70652) following public and congressional response. On 6 July 2026 DEA issued a new notice of intent (91 FR 40917, docket DEA-1570) proposing temporary Schedule I placement of 7-hydroxymitragynine above a specified threshold: more than 0.050% of 7-hydroxymitragynine on a dry-weight basis in botanical Mitragyna speciosa, or more than 0.050% by weight or volume, or more than 1.00 mg per article, in synthetic material and in extracts, concentrates, edibles or pressed pills. HHS was notified by letter of 24 February 2026, and the temporary order was to publish on or after 5 August 2026. A parallel notice the same day (91 FR 40909) covers mitragynine pseudoindoxyl, MGM-15 and MGM-16. The shift recorded here is in the object of regulation: from the plant and its alkaloids in 2016 to a concentration of one metabolite in 2026.
Source
DEA 81 FR 59929 (31 August 2016); 81 FR 70652 (13 October 2016); 91 FR 40917 (6 July 2026, docket DEA-1570)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
The retail market moved from leaf to metabolite, at up to 700 mg a dose
In plain words
A survey of 250 products sold between late 2024 and early 2025 found 7-hydroxymitragynine content ranging from 1 mg to 700 mg in a single serving. The plant itself contains only traces of it.
What was measured
7-hydroxymitragynine content per serving across 250 surveyed products, and postmortem and clinical case counts from the DEA TOX programme
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The DEA notice of intent summarises an investigation identifying 250 products sold between September 2024 and February 2025, most commonly chewable or sublingual tablets, marketed for general wellbeing and focus. 7-hydroxymitragynine content ranged from 1 mg to 700 mg per dose or serving, with an average cost of about $3.97 per dose. DEA notes that 7-hydroxymitragynine occurs only in trace amounts in Mitragyna speciosa, that it can be made from mitragynine in a single chemical step, and that synthetic and naturally occurring 7-hydroxymitragynine are chemically identical, so the pharmacology does not depend on the source. Separately, the DEA TOX programme has identified 7-hydroxymitragynine in 85 cases since 2019 — 55 fatal, 30 non-fatal, median age 36, average concentration 463.23 ng/mL — frequently alongside fentanyl, benzodiazepines such as bromazolam, or ketamine. The market described here did not exist when the 2016 scheduling attempt was withdrawn.
Source
DEA notice of intent, 91 FR 40917 (6 July 2026), product-survey and DEA TOX sections
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
About two million American adults used it in a year
In plain words
A weighted national survey of nearly sixty thousand adults put past-year kratom use at 0.8% — roughly two million people — with lifetime use at 1.3%.
What was measured
Weighted past-year and lifetime prevalence of kratom use in US adults, n=59,714
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Schimmel et al. analysed the Survey of Non-Medical Use of Prescription Drugs programme, a validated non-probability online survey, across the third quarter of 2018 and the first quarter of 2019, with 59,714 respondents aged 18 or over weighted to represent 252,063,800 US adults. Past-year kratom use was 0.8% (95% CI 0.7-0.9), representing 2,031,803 adults; lifetime use was 1.3% (95% CI 1.2-1.4), or 3,353,624 adults. Users were younger (mean 35 years, p < 0.001), more often male (61.0% versus 48.6%, p < 0.001), more often students (14.1% versus 7.5%) and health-care professionals (9.7% versus 4.5%), and less often degree holders (33.4% versus 42.6%). This is a non-probability internet panel weighted to the population, which is a weaker design than a household probability sample, and the estimate should be read with that limitation attached.
Written into the record, not signed off as a reviewed claim
Traditional-use safety arguments do not describe the current products
In plain words
Kratom leaf has been chewed in Southeast Asia for a very long time with little recorded harm. That history says nothing about a sublingual tablet delivering hundreds of milligrams of the active metabolite.
What was measured
That the safety record of traditional leaf preparations describes the risk of concentrated 7-hydroxymitragynine products, or that the postmortem series describes the risk of leaf
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The most common argument for kratom's safety is its long history of use as chewed or brewed leaf in Thailand, Malaysia and Indonesia. Leaf contains mitragynine, which is not itself a µ-opioid agonist in the functional assays, plus trace 7-hydroxymitragynine, and delivers both slowly with self-limiting nausea. The products DEA surveyed in 2024 and 2025 deliver up to 700 mg of 7-hydroxymitragynine sublingually, bypassing both the leaf matrix and first-pass metabolism, and DEA states that synthetic and plant-derived 7-hydroxymitragynine are pharmacologically identical. Extrapolating a safety record from the first exposure to the second is a category error, and this record files it as an inference in the traditional-use direction while noting the same error is made in reverse when the postmortem series is used to characterise leaf.
Source
DEA notice of intent 91 FR 40917 (6 July 2026), comparison of botanical and concentrated articles
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
CYP3A4 makes the active metabolite, so interactions are pharmacokinetic
In plain words
The liver enzyme CYP3A4 converts mitragynine into the compound that acts on the opioid receptor. Anything that changes that enzyme changes how much opioid effect a given amount of leaf produces.
What was measured
Cytochrome P450 isoform contributions to mitragynine metabolism and inhibition of CYP enzymes by kratom alkaloids in vitro
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Metabolite profiling in human liver microsomes and recombinant enzyme systems identified the cytochrome P450 isoforms responsible for mitragynine metabolism, with CYP3A4 the principal contributor to the oxidation that yields 7-hydroxymitragynine among other products. Kratom alkaloids were separately shown to inhibit several cytochrome P450 enzymes in vitro, so the interaction potential runs in both directions. The practical consequence is that the opioid effect of a fixed dose of leaf is not fixed: it depends on hepatic enzyme activity and on co-administered inhibitors and inducers. This is the same metabolic-activation pattern as codeine, where the parent is weak and a CYP-generated metabolite carries the µ-opioid effect, and it produces the same variability between people.
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The older medicine-wide conclusion held in this record
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Mitragynine is not the opioid — its oxidised metabolite is, and the concentrated 7-hydroxymitragynine products that appeared after 2023 deliver up to 700 mg of that metabolite in one dose, which is why DEA is now trying to schedule the metabolite above a concentration threshold rather than the plant.
Recorded evidence blocks (0)
Where it is registeredIdentifiers, relations and other names
No approved product. Sold as leaf powder, capsules, extracts and, since about 2023, as concentrated 7-hydroxymitragynine tablets, gummies and sublingual films
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This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.