Mitragynine, the main alkaloid in kratom leaf, has no settled half-life in people. Six human studies have estimated it, in a combined total of about 120 people given an active dose, and their estimates run from under 9 hours to almost 68. Much of that spread appears to come from how the studies were run rather than from the people in them.
The second question has a clearer answer. The human body does convert some mitragynine into 7-hydroxymitragynine (7-OH), the more potent opioid-like alkaloid, and the liver enzyme CYP3A4 does much of that work. In the human studies, 7-OH in the blood reached roughly a tenth to a third of the mitragynine level. What that small amount contributes to kratom’s effects in people has not been measured.
This is an evidence review. Each finding is labelled by the tier of evidence it comes from: anecdote, then surveys and case reports, then animal and test-tube (in vitro) studies, then human observational studies, then controlled human trials. The human pharmacokinetic studies below are small, and most of them did not compare kratom with a placebo, so “human data” here means a few dozen people, not a population.
What pharmacokinetics measures
Pharmacokinetics is the study of what the body does to a substance: how fast it is absorbed, where it goes, how it is broken down, and how it leaves. The figure most often quoted is the half-life, the time it takes for the concentration in the blood to fall by half.
Two cautions apply to every half-life in this article.
The first is the sampling window. A half-life is estimated from the slope of the falling blood concentration. If blood is drawn for 24 hours and the substance is still there at the end, the estimate rests on a short stretch of the curve and is easy to get wrong.
The second is the terminal half-life. Mitragynine leaves the blood quickly at first, as it moves into tissues, and then much more slowly as it seeps back out. The terminal half-life describes the slow tail. It is a real property of the drug, but it does not by itself tell you how much builds up in the blood with daily use, a point two of the studies below make about their own data.
The human half-life studies
These are all the human pharmacokinetic studies of mitragynine with published half-life figures that we found and read. Every number in the right-hand column is a terminal half-life for mitragynine taken by mouth.
| Study | People | Form and mitragynine dose | Blood sampled for | Mitragynine half-life |
|---|---|---|---|---|
| Trakulsrichai et al., 2015, Thailand | 10 men, all long-term daily users; 9 analysed | Tea brewed from fresh leaf, 6.25 to 23 mg, after 7 days of daily tea | 24 hours | Mean 23.2 hours (standard deviation 16.1) |
| Tanna et al., 2022, US | 6 healthy adults (3 men, 3 women), 5 completed; all had used kratom before | Tea from 2 g of leaf powder, about 39 mg | 120 hours | Median 45.3 hours (range 31.9 to 50.2) |
| Mongar et al., 2024, Thailand | 16 healthy adults (5 men, 11 women) with no kratom history; tables report 15 | Fresh tea, 23.6 mg | 72 hours | Geometric mean 8.72 hours |
| Huestis et al., 2024, Canada | 12 healthy adults per dose (13 at the highest), new to kratom or no use for a year; 8 to 11 per dose had data after daily dosing | Capsules of dried leaf powder, 6.65 to 53.2 mg, once and then daily for 15 days | Up to 10 days after a single dose | Single dose: mean 8.5 hours at 6.65 mg, rising to 43.4 hours at 53.2 mg. Daily dosing: up to a mean of 67.9 hours |
| Huestis et al., 2026, Canada | 12 healthy adults per dose (10 or 11 analysed after one dose; 11, 11 and 5 after daily dosing) | Capsules of an extract, 39.5% mitragynine, 9.9 to 59.2 mg, once and then daily for 15 days | Up to 10 days after a single dose | Single dose: mean 13.5 hours at 9.9 mg, rising to 54.7 hours at 59.2 mg. Daily dosing: 40.9 to 64.8 hours |
| Kanumuri et al., 2026, US | 4 adults taking kratom at least five days a week | Each person’s own product, 26.6 to 54.1 mg | 24 hours | 17.1 to 35.1 hours in the four people, with mitragynine already in their blood before the dose |
Four things in that table matter more than any single figure in it.
A 24-hour window is the reason the first study’s number is in doubt. The 2015 Thai study, the first in humans, reported a terminal half-life of about a day from blood drawn over one day. Tanna and colleagues, writing in 2022, said the figure “was near or exceeded the sample collection period”, and questioned whether it, and the measures calculated from it, could be relied on. Their own study sampled for five days and found a median of 45 hours, in five people. The four-person 2026 study also sampled for 24 hours, in people who already had mitragynine in their blood from earlier use, so its figures carry the same caution.
Within one study, the half-life rises with the dose. In the 2024 leaf-powder trial the mean went from 8.5 hours at the lowest dose to 43.4 hours at the highest, and individual single-dose estimates ranged from 1.5 to 84.5 hours. The extract trial showed the same pattern. The authors of both attribute much of this to the assay: at low doses, mitragynine falls below what the test can detect sooner, so the slow tail is cut off and the half-life looks short. The 2026 paper adds that the pattern “also suggested possible enzyme saturation”, meaning the body may clear mitragynine less efficiently at higher doses. It does not settle which explanation is right.
The long terminal half-life overstates how much builds up. If mitragynine really halved only every two or three days, daily dosing should pile it up in the blood. The 2024 trial found accumulation ratios of 1.1 to 1.3 for peak concentration and 1.6 to 1.9 for total exposure, which the authors call low to moderate, and steady state, the point where daily intake and elimination balance, within 8 to 9 days. Its authors wrote that these results “contradict the observed long terminal T1/2”, and both Huestis papers call for an “operational” half-life that would predict accumulation better. Nobody has published one for mitragynine.
The people studied are not the people who use kratom most. The trials gave at most 59.2 milligrams of mitragynine in a dose. Only the 2015 study and the four-person 2026 study enrolled regular users. Together the studies are mostly young, healthy adults, with no published data for older people, pregnancy, or liver or kidney disease.
Both Huestis trials were randomised, double-blind and placebo-controlled, the strongest design on the evidence hierarchy. The half-lives and blood ratios quoted here, though, come only from the people who took kratom; the placebo groups add nothing to those numbers, so as evidence they are closer to careful human observation than to a trial result. Both trials were commercially sponsored. A company selling the leaf product tested paid for the 2024 trial, and all four authors were paid consultants to it; two were also consultants to the American Kratom Association, and one works for a pharmaceutical company. The same company funded the human research in the 2026 trial; the company that supplied the extract paid for the writing and publication, all five authors are its consultants, and one works for it. The 2022 Tanna study was funded by the US National Institutes of Health and its authors declared no conflicts.
The figures that circulate
Shorter half-lives circulate too. A 2019 systematic review (Ya and colleagues, Asian Journal of Psychiatry), summarising rat and human studies together, gave a half-life of 3 to 9 hours. We read its abstract only. That review predates every human study in the table except the first, so it cannot reflect them. Any single half-life figure for mitragynine, short or long, should come with the study, the number of people, and the dose. Without those it cannot be checked.
How the body breaks mitragynine down
Very little mitragynine leaves the body unchanged. In the 2015 Thai study, 0.14 percent of the dose appeared unchanged in urine; in the 2022 US study, about 0.1 percent. The rest is broken down, mostly in the liver, by enzymes in the cytochrome P450 family (CYP for short).
In the test tube (tier 3). Three groups incubated mitragynine with human liver preparations or with individual human CYP enzymes grown in the laboratory:
- Kamble and colleagues (2019, Xenobiotica) found thirteen metabolites in human liver preparations. They report that metabolism “was predominantly carried out through the CYP3A4 with minor contributions by CYP2D6 and CYP2C9”, and that CYP3A4 formed 7-OH. We read the abstract only.
- Kruegel and colleagues (2019, ACS Central Science) found that the CYP3A4 enzyme broke down nearly all the mitragynine in an hour (2 percent remaining at 60 minutes), while four other major CYP enzymes did little. In human liver preparations, ketoconazole, a drug that blocks CYP3A, strongly inhibited both the breakdown of mitragynine and the formation of 7-OH. We read the full text. The work was partly funded by the American Kratom Association, a kratom advocacy group, and several authors hold patent applications on mitragynine-like compounds.
- Basiliere and Kerrigan (2020, Journal of Analytical Toxicology) found four CYP enzymes (2C18, 2C19, 2D6 and 3A4) acting on mitragynine, and report that 7-OH “was produced exclusively by 3A4”. The most abundant metabolite in their experiments, and in urine from kratom users, was a different one, 9-O-demethylmitragynine. We read the abstract only.
The three agree that CYP3A4 makes 7-OH. They do not agree on what else matters: Kruegel’s group concluded that demethylation, the route that makes 9-O-demethylmitragynine, is “only a minor pathway” of liver metabolism, while the other two groups found it to be a major one.
In people (tier 4). The 2026 study in four regular users used a test for seventeen alkaloids and metabolites on their blood. Its authors name two other metabolites, mitragynine 16-carboxylic acid and 9-hydroxycorynantheidine, as “the major circulating metabolites”. By area under the curve, a measure of total exposure, these reached 20 to 42 percent and 15 to 27 percent of mitragynine. 7-OH reached 11 to 13 percent. So in the blood of these four people, 7-OH was one of several metabolites and not the largest.
Does the body make 7-OH from mitragynine?
Yes. Two lines of human evidence point there, and one of them tests the mechanism directly.
7-OH appears in the blood after leaf that contains almost none. The 2024 leaf-powder trial used powder in which 7-OH was below 0.01 percent, and the 2022 tea study used powder that contained only a trace. Both found 7-OH in blood. The 2022 authors wrote that it “was assumed to be largely formed from mitragynine in vivo”; the 2024 authors attribute it to mitragynine metabolism, given how little the powder contained. The amounts, by each paper’s own measure:
| Study | 7-OH as a share of mitragynine in blood |
|---|---|
| Tanna 2022, tea, 5 people | Peak 27%, total exposure 24% (medians) |
| Huestis 2024, leaf powder, 12 per dose | Mean concentration ratio 20 to 31% after one dose, 15 to 21% after 15 daily doses |
| Huestis 2026, extract, 10 or 11 per dose after one dose; 11, 11 and 5 after daily doses | Peak 16 to 23% after one dose, 12 to 21% after daily doses (means) |
| Mongar 2024, tea, 15 people | Peak about 9%, total exposure about 13% over 72 hours and 20% extrapolated beyond it |
| Kanumuri 2026, own products, 4 regular users | Total exposure 11 to 13% |
In both Huestis trials the share was higher after a single dose than after daily dosing, and higher at lower doses. The 2026 paper’s abstract states the opposite for single and daily doses; its results section and its own table support the reading given here. Its authors suggest that at higher doses the conversion to 7-OH “was not as efficient”, which is consistent with the enzyme saturation idea but does not prove it.
Blocking CYP3A4 in people cuts 7-OH (a small, unblinded human experiment). Mongar and colleagues (2024) gave 16 healthy Thai volunteers kratom tea twice: once alone, and once after four days of itraconazole, an antifungal drug that strongly blocks CYP3A4. With itraconazole, mitragynine’s peak rose about 1.5 times and 7-OH fell. The paper reports that 7-OH’s peak fell by 56 percent and its 72-hour exposure by 43 percent. The geometric means in the paper’s own table imply larger falls, about two thirds for both, and the paper does not explain the difference. In either reading, less CYP3A4 activity meant less 7-OH. The authors call this “the first evidence of metabolic conversion of mitragynine to 7OH in humans”. It is one study of 15 analysed people, it has no placebo arm, and it gave a single 23.6 mg dose.
The animal evidence does not line up neatly (tier 3). In rats given the CYP3A blocker ketoconazole (Kamble and colleagues, 2023), exposure to mitragynine rose by 120 percent and exposure to 7-OH also rose, by 130 percent, the opposite of the human itraconazole result. The authors concluded that both compounds are cleared through CYP3A in rats and that 7-OH must also be formed by other routes. In mice, blocking CYP3A reduced the slowing of breathing caused by mitragynine but not that caused by 7-OH (Hill and colleagues, 2022), which suggests that in mice part of mitragynine’s effect runs through 7-OH. In female beagle dogs given mitragynine by mouth, 7-OH reached the blood; given it intravenously, 7-OH stayed below the limit of measurement (Maxwell and colleagues, 2020). The intravenous dose was fifty times smaller than the oral one (0.1 against 5 milligrams per kilogram), so that difference may partly reflect the dose and the limits of the test. The dog study also found that 69.6 percent of an oral dose reached the blood. No study has given mitragynine intravenously to people, so that figure does not exist for humans. We read the abstracts of the rat and dog studies and the full text of the mouse study.
Whether the 7-OH matters
This is the part the human evidence does not reach.
7-OH binds the brain’s main opioid receptor more strongly than mitragynine (see kratom’s alkaloids). Whether the small amount made in the body drives any of kratom’s effects in people has not been tested. The two mouse studies that tried to answer it disagree. Kruegel’s group (2019) concluded that 7-OH is “a key mediator” of mitragynine’s pain-relieving effect in mice. Berthold and colleagues (2022) found that at doses that relieved pain equally, the brain level of 7-OH formed from mitragynine was 11 times lower than after 7-OH itself, and concluded that it has “a negligible role” in mice. We read Berthold’s abstract only.
There is a further complication specific to humans. In a test-tube study (Kamble and colleagues, 2020), 7-OH was stable in rodent and monkey plasma but in human plasma turned into another compound, mitragynine pseudoindoxyl, which the authors describe as an opioid “even more potent than either mitragynine or 7-HMG” (their abbreviation for 7-OH). We read the abstract only. The four-person 2026 study measured pseudoindoxyl in the blood of all four regular users, at a total exposure of 4 to 9 percent of mitragynine’s. What it contributes in people is not known.
Because species differ in exactly the steps that make and break down 7-OH, a finding in mice or rats does not transfer directly to people. Several of these papers say so themselves.
What this means for interactions
CYP3A4 also breaks down many prescription medicines. The human studies show the relationship runs both ways: blocking CYP3A4 with itraconazole raised mitragynine and lowered 7-OH (Mongar 2024), and in a separate study of 12 healthy adults a single 2 g dose of kratom tea raised blood levels of midazolam, a sedative cleared by CYP3A, by about 39 percent in total exposure and 50 percent at the peak (Tanna and colleagues, 2023). The authors attribute this mainly to CYP3A in the gut wall rather than the liver. What this means in practice, and which combinations have been studied, is covered in kratom and drug interactions. We found no human study of what a drug that speeds CYP3A4 up does to mitragynine or 7-OH.
Putting the tiers together
| Question | Best evidence | Tier | What it shows |
|---|---|---|---|
| What is mitragynine’s half-life? | Six small human studies, two inside placebo-controlled trials | 4 | Estimates from under 9 to about 68 hours, depending heavily on dose and sampling window |
| Does it build up with daily use? | Two industry-funded trials, 5 to 13 people per dose | 4 | Less than the long half-life predicts; steady state in 8 to 9 days |
| Which enzyme breaks it down? | Human liver preparations and enzymes in the test tube | 3 | Mainly CYP3A4, with smaller roles for others |
| Does the body make 7-OH from it? | One small human CYP3A4-blocking experiment, plus 7-OH in blood after low-7-OH leaf | 4 | Yes, partly through CYP3A4 |
| How much 7-OH? | Five human studies | 4 | About a tenth to a third of the mitragynine level |
| Does that 7-OH cause effects in people? | No human study; mouse studies disagree | 3 | Unknown |
| How much of an oral dose reaches the blood? | One dog study | 3 | Not known in humans |
What we do not know
How long mitragynine takes to leave the body at the doses regular users take. The trials stop at 59.2 milligrams in a dose, and the half-life estimates move with the dose.
Whether the dose-dependence of the half-life is an artefact of the assay, a sign that metabolism saturates, or both.
How mitragynine behaves in older people, in pregnancy, or in people with liver or kidney disease. No human study has looked.
How much people differ. CYP3A4 activity varies between individuals and is changed by many drugs and some foods, but no study has been large enough to describe that variation for mitragynine.
How much of an oral dose reaches the blood in people, and how much reaches the brain.
Whether the 7-OH, or the pseudoindoxyl, made in the human body contributes to kratom’s effects.
How we found these papers
Europe PMC was searched on 29 October 2026 with the query (TITLE_ABS:(kratom OR mitragynine OR "Mitragyna speciosa" OR "7-hydroxymitragynine")) AND (TITLE_ABS:(pharmacokinetic* OR "half-life" OR "half life" OR metabolism OR metabolite* OR CYP3A4 OR "cytochrome P450" OR clearance OR bioavailability OR "plasma concentration*" OR toxicokinetic* OR disposition OR absorption OR elimination)), which returned 206 records. We screened the titles for human pharmacokinetic
studies, enzyme studies of mitragynine metabolism, and animal studies of 7-OH formation, and set
aside plant chemistry, analytical methods without human data, reviews, and modelling papers built
on other studies’ data.
We read in full: the 2015 Thai study, the 2022 tea study, the 2024 itraconazole study, both Huestis trials, the four-person 2026 study, the Kruegel 2019 paper and the Hill 2022 mouse study. Of the 2023 interaction study we read the abstract and the methods. We read the abstracts only of the two 2019 and 2020 enzyme papers by Kamble and by Basiliere, the 2020 human plasma study, the rat, dog and Berthold mouse studies, and the 2019 systematic review, and we do not characterise anything in them beyond what their abstracts state.
A 2026 dose-finding study of leaf in 40 recreational drug users, whose authors are at the US Food and Drug Administration (Reissig and colleagues), also measured blood levels. Its abstract reports no half-life or 7-OH figures, and we could not obtain the full text, so its pharmacokinetic results are not used here. A 2017 master’s thesis from a Thai university, cited by the itraconazole study as reporting a similar half-life in healthy volunteers, has not been published in a journal and we have not read it.
This page is not medical advice.
If you know of a human pharmacokinetic study of mitragynine that we have missed, write to editorial@wikikratom.com.