Kratom alkaloids and pharmacology: what the research says about mitragynine and 7-OH

Kratom’s effects come from a family of indole alkaloids, chiefly mitragynine and the far smaller amount of 7-hydroxymitragynine that the body makes from it. This guide summarizes what the published pharmacology says about those compounds: where they act, how they differ from classical opioids, and what is still unresolved. It is written for readers who want to understand lab results and regulatory debates, not as health guidance. Nothing here is advice about using kratom.

Last reviewed: November 9, 2026. Part of the KratomSource knowledge base.

The alkaloids in the leaf

More than 40 alkaloids have been isolated from Mitragyna speciosa. In dried leaf powder, mitragynine dominates, typically around 1–2% of dry weight and roughly two-thirds of total alkaloids. The next most abundant are paynantheine, speciogynine and speciociliatine, each at a fraction of a percent. 7-hydroxymitragynine (7-OH) is present in fresh and properly dried leaf only in trace amounts, generally below 0.05% of dry weight, and higher levels in a powder point to oxidation during processing or deliberate addition. This is why lab panels report mitragynine and 7-OH separately, and why the US DEA’s 2026 proposal to schedule concentrated 7-OH used 0.05% as the threshold distinguishing leaf from extract; our 7-OH guide covers that rule.

Where mitragynine acts

Mitragynine is a partial agonist at the mu-opioid receptor, the same receptor targeted by morphine, with lower intrinsic efficacy. Work from Columbia University and collaborators (Kruegel et al., Journal of the American Chemical Society, 2016) showed that mitragynine and 7-OH activate the receptor’s G-protein signalling pathway with little or no recruitment of beta-arrestin-2, the pathway associated in animal studies with respiratory depression and constipation. This “biased agonism” is the basis for the frequently repeated claim that kratom alkaloids are safer than classical opioids. It is a laboratory finding about signalling, replicated in several labs, and it is not the same as a demonstration of safety in people.

Mitragynine is also active beyond opioid receptors. It binds alpha-2 adrenergic receptors (the target of clonidine), has activity at serotonin receptors, and at low concentrations shows stimulant-like effects in animals that are not opioid-mediated. Pharmacology reviews describe the overall profile as dose-dependent: stimulant-like at lower exposures and opioid-like at higher ones, which matches what survey respondents describe and what traditional use in Southeast Asia reports. The mixed receptor profile is also why kratom is difficult to place in a single drug category.

7-hydroxymitragynine: metabolite and concentrate

7-OH is several times more potent than mitragynine at the mu-opioid receptor and, in animal studies, more potent than morphine on some measures. Research from 2019 onward (Kruegel et al., ACS Central Science) showed that most of the 7-OH in the body after taking leaf kratom is formed from mitragynine by liver enzymes (CYP3A4), not ingested as such. Animal work by Hemby and others found that mitragynine itself showed little reinforcing effect while 7-OH did, which is one reason regulators and researchers treat concentrated 7-OH products as a different risk category from leaf powder. KratomSource does not review or score 7-OH concentrates for that reason.

Respiratory depression

The most dangerous effect of classical opioids is suppression of breathing. Animal studies of mitragynine have generally found a much smaller effect on respiration than morphine at equivalent analgesic doses, and a 2022 review commissioned with industry funding reached the same conclusion from the available data. The US CDC’s analysis of overdose deaths from 2016–2017 found kratom detected in 152 of 27,338 deaths (0.56%); in 91 of those a medical examiner listed kratom as a cause, but almost all involved other substances (fentanyl in about two-thirds), and only seven had kratom as the sole substance detected. The honest summary is that leaf kratom appears far less likely than opioids to stop breathing on its own, that deaths with kratom as the only substance are rare but documented, and that the combination of kratom with opioids, benzodiazepines or alcohol is where most of the recorded harm sits.

Drug interactions reported in the literature

Mitragynine is metabolized by CYP3A4 and CYP2D6 and inhibits both in laboratory assays, so case reports and reviews flag the possibility of interactions with drugs that depend on those enzymes, and additive effects with other sedatives. Case reports have described liver injury (cholestatic hepatitis) in a small number of users, seizures mostly in combination with other substances, and interactions with medications such as quetiapine and certain antidepressants. These are case reports, not controlled studies, and the rate is unknown; they are the reason every reputable source, including this one, says to involve a physician or pharmacist in any decision about kratom alongside medication.

Dependence

Regular use produces tolerance and a withdrawal syndrome on stopping, described in surveys and Malaysian cohort studies as generally milder than opioid withdrawal but real: irritability, muscle aches, runny nose, insomnia and low mood, typically peaking within the first few days. A proportion of regular users meet diagnostic criteria for a substance use disorder; large US surveys put that at a minority of respondents, with most reporting they could stop without significant difficulty and a smaller group reporting marked difficulty. Our effects, dosage literature and safety guide gives the survey figures and sources.

What is not known

• There are no large randomized controlled trials of kratom in humans. The human evidence is surveys, observational cohorts, case reports and a small number of controlled laboratory studies.
• Long-term effects of daily use over years are not characterized beyond the Malaysian cohort work.
• Alkaloid content varies widely between products and batches, so “a dose of kratom” is not a defined quantity of any compound without a certificate of analysis.
• The relative contribution of minor alkaloids to effects and risks is largely unstudied.

The World Health Organization’s Expert Committee on Drug Dependence reviewed kratom in October 2021 and concluded there was insufficient evidence to recommend a critical review for international scheduling, while asking for continued surveillance. The US FDA has taken the position that kratom has no approved use and warns against it; Health Canada has not authorized any kratom product for sale as a health product. Those positions are described on our legal map and enforcement tracker.

Sources

• Kruegel AC, Grundmann O. The medicinal chemistry and neuropharmacology of kratom. Neuropharmacology 2018;134(Pt A):108–120. PubMed 28830758.
• Kruegel AC et al. Synthetic and receptor signaling explorations of the Mitragyna alkaloids: mitragynine as an atypical molecular framework for opioid receptor modulators. J Am Chem Soc 2016;138(21):6754–6764.
• Kruegel AC et al. 7-Hydroxymitragynine is an active metabolite of mitragynine and a key mediator of its analgesic effects. ACS Cent Sci 2019;5(6):992–1001.
• Hemby SE et al. Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids mitragynine and 7-hydroxymitragynine. Addict Biol 2019;24(5):874–885.
• Olsen EO et al. Notes from the field: unintentional drug overdose deaths with kratom detected, 27 states, July 2016–December 2017. MMWR 2019;68(14):326–327. CDC.
• Henningfield JE et al. Respiratory effects of oral mitragynine and oxycodone in a rodent model. Psychopharmacology 2022;239:3793–3804.
• WHO Expert Committee on Drug Dependence, 44th report (2021), kratom pre-review.
• Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend 2014;139:132–137.

Frequently asked questions

Is kratom an opioid?

Its main alkaloid, mitragynine, is a partial agonist at the mu-opioid receptor and also acts on adrenergic and serotonin receptors. Pharmacologists describe it as an atypical opioid with a mixed profile rather than a classical one.

What is 7-hydroxymitragynine?

A minor leaf alkaloid, below 0.05% in natural leaf, and the main active metabolite the liver produces from mitragynine. It is several times more potent at the opioid receptor, which is why concentrated 7-OH products are treated as a separate risk category.

Does kratom cause respiratory depression?

Animal studies show much less respiratory depression than morphine at comparable doses. Deaths with kratom as the only substance detected are rare but documented; most recorded deaths involve kratom combined with opioids or sedatives.

Does kratom interact with medications?

Mitragynine inhibits the liver enzymes CYP3A4 and CYP2D6 in laboratory studies, and case reports describe serious interactions with sedatives and some psychiatric medications. Anyone taking medication should involve a physician or pharmacist.