The US Agencies' 7-OH Threshold – and What Experts Argue Against It
On July 6, 2026, two US agencies opened a proceeding that has no precedent in the field surrounding Mitragyna speciosa: what is to be scheduled is not the plant, but a content threshold. The response from the scientific side is just as remarkable. In peer-reviewed journals, pharmacologists have explicitly argued against scheduling, and the agencies themselves draw a line between untreated leaf material and enriched preparations. This article places both side by side: the proposal, the scientific objections, and where the proceeding currently stands.
Scheduling a plant is not the same as scheduling a content threshold
Classical controlled-substance law works with lists. What appears on those lists are names: a substance, a class of substances, occasionally an entire plant together with its parts. Classification is therefore binary. Something is on the list or it is not, and that question can be answered by identifying the material botanically or chemically.
A content threshold works differently. There, the same substance from the same plant sits on both sides of the line, and which side applies depends solely on how much of it a given article contains. Two samples can be botanically identical, come from the same harvest and look the same — one falls under the rule, the other does not. The construction is not entirely new: hemp law has long shown that a limit for tetrahydrocannabinol on a dry weight basis decides whether a plant counts as industrial hemp. For Mitragyna speciosa the approach is new, and it shifts the decisive step from identifying the species to measuring in the laboratory.
The agencies themselves distinguish between leaf and concentrate
This point is regularly lost in press coverage, yet it is stated explicitly in the documents. The US Food and Drug Administration records that the measures target concentrated and synthetic 7-OH products and are not intended to be applied to natural leaf material containing only naturally occurring trace amounts. By the agencies' own wording, the proceeding is therefore directed at a composition, not at the plant.
The quantitative background for this is unambiguous. The alkaloid fraction of the leaf — that is, the totality of the nitrogen-containing plant constituents it holds — is dominated by mitragynine. 7-hydroxymitragynine, by contrast, is a trace alkaloid and occurs in untreated leaf material in very small proportions, far below what mitragynine accounts for.
Chemically, 7-hydroxymitragynine is an oxidation product of mitragynine: on the indole skeleton, position 7 carries an additional hydroxyl group. This kinship has two consequences, both of which are named in the DEA notice. First, the substance arises in the body as an oxidized metabolite of mitragynine. Second, it can be produced from mitragynine in a single-step chemical reaction. Because the passage from one molecule to the other is chemically so short, the content of a given batch depends not only on the plant, but also on how the material was dried, stored and processed.
Why the dividing line also has a pharmacological basis
Distinguishing between the parent substance and its conversion product does not rest on quantitative ratios alone. A 2022 paper by Hill and colleagues, published in the British Journal of Pharmacology, examined the relationship in a mouse model — and produced a finding that turns out to be favorable for the parent substance.
What was measured was respiration in awake, freely moving animals after oral administration. For mitragynine, the respiratory depressant effect showed a ceiling effect: doses above 10 milligrams per kilogram produced no further increase in effect. For 7-hydroxymitragynine the picture was different, with the effect rising along with the dose. When the researchers inhibited the enzyme CYP3A, the respiratory depressant effect of mitragynine decreased, while that of 7-hydroxymitragynine did not. From this the authors conclude that conversion into the more potent substance carries the effect — and that the limited rate of that conversion caps it at the upper end. In their words, what is at work here is a "metabolic saturation" which, in their assessment, could underlie an improved safety profile for mitragynine.
This is a finding from an animal model and not a statement about human beings. As a finding it is notable because it shows the same property from two sides: the fact that mitragynine only becomes the more potent molecule through metabolism makes measurement and comparison harder — yet in the experiment it is at the same time what limits the effect. A product to which 7-hydroxymitragynine has been added directly bypasses that intermediate step. It is precisely at this point that the agencies take hold.
How enrichment comes about
The notice names, in essence, three routes by which a product can contain more 7-hydroxymitragynine than the starting leaf.
- Concentrating. Extracts and concentrates remove plant mass and leave the alkaloids behind. The proportion rises without a single molecule having to be newly formed.
- Converting. Chemical or thermal treatment can transform mitragynine into 7-hydroxymitragynine, either deliberately or as a side effect. The DEA speaks of processes that lead to chemical conversions.
- Adding. Isolated or synthetically manufactured substance is added to a product. Here the measured content no longer has anything to do with the original plant.
The dosage forms named as affected are expressly extracts, concentrates, processed edibles and pressed tablets.
What was put forward — and how far the proceeding has gone
On July 6, 2026, three documents appeared in the Federal Register. The DEA announced that it intended to place 7-hydroxymitragynine above a defined threshold temporarily in Schedule I, and alongside it three related synthetic substances — mitragynine pseudoindoxyl, MGM-15 and MGM-16. The Department of Health and Human Services additionally published a request for comment which put up for discussion, among other things, whether the proposed value is the right one.
The threshold itself is split in two in the text. For plant material it applies as a content of more than 0.050 percent 7-hydroxymitragynine on a dry weight basis — not relative to the alkaloid fraction, but to the dried mass as a whole. For synthetically obtained or further processed material a second criterion is added: more than 0.050 percent, expressed as weight by weight, weight by volume or volume by volume, or more than 1.00 milligram of 7-hydroxymitragynine per article.
The status of the proceeding as of September 21, 2026 is differentiated, and it is frequently reported in abbreviated form:
| Subject | Status |
|---|---|
| Mitragynine pseudoindoxyl, MGM-15, MGM-16 | Published as a final rule on August 26, 2026; temporary placement in Schedule I |
| 7-hydroxymitragynine above a threshold | Still an announcement; no final order published |
| Comment proceeding on the threshold | Extended on August 26, 2026; deadline September 10, 2026 |
Under US law a temporary placement runs for two years and can be extended by a further year for as long as the regular proceeding is under way. Since the final order on the threshold has not appeared to date, the figure of 0.050 percent is not settled either: it is the proposed value, not the one in force.
The scientific objections — what the literature sets against it
In 2018, Jack E. Henningfield and colleagues published an assessment in Psychopharmacology structured along the eight factors of the Controlled Substances Act — the very framework that US law prescribes for a scheduling decision. Their conclusion: the abuse potential of mitragynine lies within the range of many uncontrolled substances, and there is no evidence of an imminent hazard to public health.
In 2022, Frontiers in Pharmacology carried the update under the title "Kratom Abuse Potential 2021: An Updated Eight Factor Analysis". In it, Henningfield, Wang and Huestis evaluated more than 100 papers published since January 2018. Three points from that work bear directly on the present proceeding:
- The authors argue explicitly against scheduling under the Controlled Substances Act and recommend instead a form of regulation that addresses contaminated, adulterated and inaccurately marketed products.
- Describing mitragynine as an opioid "analogue" or as a "narcotic-like opioid" is, on their evaluation, not compatible with the overall body of evidence. Among other things they point out that the alkaloids examined do not recruit β-arrestin-2 at the opioid receptors — a behavior that sets them apart from classical opioids.
- As a risk of scheduling they expressly name consequences for public health, because a prohibition shifts demand onto unregulated markets.
The current proceeding has drawn scientific objections of its own. The pharmacologist Christopher McCurdy of the University of Florida told Spectrum News that lumping very different products together under a shared label has created considerable confusion — among physicians, among consumers, and in the toxicological as well as the policy debate; for MGM-15, for instance, not even animal safety data are available so far. In May 2026 the R Street Institute argued in a paper for proportionate regulation that distinguishes between natural products, concentrated 7-OH preparations and genuine synthetic analogues; the available evidence, it held, supports neither equating concentrated 7-OH with heroin or fentanyl nor treating it as free of risk.
How deaths are attributed in the statistics
Mortality figures play a large part in this debate, and they are frequently quoted without the attribution portion that belongs to them. The US Centers for Disease Control and Prevention evaluated a total of 27,338 unintentional overdose deaths across 27 states for the period from July 2016 through December 2017. Kratom was detected in 152 of the decedents; in 91 of those it was listed as a cause of death. In only seven of the 152 cases was kratom the sole substance to test positive in postmortem toxicology. The most frequent finding was fentanyl: it was listed as a cause of death in 65.1 percent of the decedents who tested positive.
The 2021 evaluation summarizes the same picture for the literature as a whole: in roughly 80 percent of cases with a kratom detection, further drugs of abuse were also detected or a history of substance use disorder was present, so that a contribution from other substances cannot be ruled out. On that basis the authors arrive at the assessment that the risk of an associated death lies orders of magnitude below that of morphine-like opioids.
How widespread use is
For the US population survey NSDUH, the 2021 evaluation reports a lifetime prevalence of 1.4 percent and a past-year prevalence of 0.7 percent; extrapolations in the literature range from 1.8 million to more than 16 million users, and the authors consider at least 10 million to be likely. On motives there is a much-cited survey by Oliver Grundmann, published in Drug and Alcohol Dependence in 2017: 8,049 people completed the questionnaire in full, 68 percent named pain as their reason and 66 percent named emotional or mental states. Surveys of this kind are self-reports from a self-selected group and are no substitute for a controlled study — as an order of magnitude for the question of what is actually being regulated, they are nonetheless informative.
A line you cannot see on the product
Whether a product lies above or below the line cannot be established with the naked eye. Two powders, two tablets, two liquids can look identical; the difference becomes visible only in the analytical report. That pushes questions to the center which otherwise seem merely technical: which analytical method was used? What does the percentage figure refer to? How representative is the sample of the batch? What measurement uncertainty attaches to the result, and what does it mean in the immediate vicinity of a limit? On top of that comes the dual nature of the criterion: a large-format product can sit below the line in percentage terms and still exceed the milligram limit per article, while a small dosage form can present the reverse case.
What this means for European suppliers — and what it expressly does not
Here clarity matters more than any nuance: US law does not apply in the European Union. The Controlled Substances Act is US federal law; a placement in Schedule I has no direct effect in Germany or in any other member state. Neither a European limit nor an obligation to align with one follows from the threshold.
The legal framework in the EU arises from other instruments — among them Regulation (EU) 2015/2283 on novel foods, national narcotics and medicines law, and the rules on contaminants and residues. These bodies of law follow systems of their own and are not altered by a US proceeding. What is directly touched, if anything, are matters with a US connection, meaning export, import or supply chains that pass through the United States.
Why the proceeding is relevant nonetheless
It is interesting less as a legal norm than as a pattern of thought. The guiding question shifts from "which plant" to "which composition". Where regulation attaches to a content threshold, it is no longer botanical origin that decides classification but the analytical result — which turns test methods, reference standards and reference bases into regulatory quantities.
Patterns of thought like this tend, in experience, to travel across borders, because they solve a problem that presents itself in the same way in many legal systems: the distinction between a traditionally traded plant material and a heavily enriched product derived from it. Whether such an approach will ever find its way into European law is an open question. What can be recorded is that the question of composition is gaining in importance — and that it cannot be answered without analytics.
Further sources: the DEA notice on the threshold of July 6, 2026 (Federal Register), the extension of the comment period to September 10, 2026 (Federal Register), the FDA's position on concentrated products (fda.gov), Hill et al., "The respiratory depressant effects of mitragynine are limited by its conversion to 7-OH mitragynine", British Journal of Pharmacology 179 (2022), 3875–3885 (PMC), Henningfield, Fant and Wang, Psychopharmacology 235 (2018), 573–589 (PubMed), Henningfield, Wang and Huestis, "Kratom Abuse Potential 2021", Frontiers in Pharmacology 12 (2022) (Frontiers), Olsen et al., MMWR 68 (2019), issue 14 (cdc.gov), Grundmann, Drug and Alcohol Dependence 176 (2017), 63–70 (PubMed), and the R Street Institute paper of May 2026 (rstreet.org).
Further reading
- What is 7-hydroxymitragynine?
- Mitragynine vs. 7-OH-Mitragynine: What Sets the Two Main Alkaloids Apart?
- Kratom in the USA: How the Community Fought Bans – and Won
- Kratom Research 2025/2026: Where Do We Stand?
- Kratom and Novel Food: What the EU Regulation Means for Buyers and Sellers
Legal notice
This article is for informational purposes only and does not constitute legal advice. Its content is not intended to encourage consumption. Laws may change; the applicable regulations and information from official bodies are authoritative. Image source: https://www.kratoein.com/