Emergency Classification of Potent Kratom-related Compounds as Schedule I Drugs by the DEA: Why Now?
Rutgers researcher, Jenny Wilkerson, describes kratom and how it is pharmacologically different from its derivative products
If you are one of the millions of Americans living with chronic pain or substance use disorders, or if you work as a biomedical researcher or clinician in these fields, you may have heard of kratom. If you have not, there is a good chance you have never encountered it at all.
What is kratom?
Kratom, or Mitragyna speciosa, is a tropical tree native to Southeast Asia. Its leaves have been used traditionally in the region for centuries, but over the past two decades kratom has developed a substantial following in the United States. People use it for a variety of reasons, including pain, energy, mood, and to manage symptoms associated with opioid withdrawal. In the U.S., it is sold in forms ranging from dried leaf and powders to capsules, extracts, and increasingly concentrated products. NIDA estimates that millions of U.S. adults have used kratom.[1]
However, outside of the people who use it, researchers who study it, and the clinicians who encounter those patients, there remains surprisingly little public awareness of what kratom is. In talking with clinicians and members of the public, I have often encountered a version of: “Kratom? I have heard of it, but I really don’t know what it is.” There has been almost an “if you know, you know” view about kratom in the United States. It has become increasingly visible in gas stations, smoke shops, supplement stores, and online markets, while remaining relatively unfamiliar to much of the broader medical community and public. One reason kratom’s relative obscurity is changing rapidly is due to the emergence of highly concentrated kratom-derived products containing 7-hydroxymitragynine (7-OH) and other chemically modified compounds. This is where an important distinction is getting lost in the current discussion: these compounds are not readily interchangeable with traditional kratom leaf.
The US government’s emergency response to synthetic 7-OH derivatives
The federal government’s current action takes that distinction one step further. The Department of Justice has temporarily placed three potent 7-OH-related compounds mitragynine pseudoindoxyl (MGPI), MGM-15, and MGM-16 into Schedule I. [6] These are chemically modified compounds with potent μ-opioid receptor activity, and the available preclinical evidence raises legitimate concerns about dependence and respiratory effects. Importantly, the Department of Justice has stated that the action is directed at these manufactured and concentrated opioid compounds, rather than traditional botanical kratom.
Although this current Department of Justice Schedule I decision does not include whole plant kratom, this does not mean kratom is harmless. Repeated kratom use can produce tolerance, dependence, and withdrawal, and there are legitimate concerns about product quality, adulteration, and interactions with other substances. The FDA does not consider kratom to be lawfully marketed as a dietary supplement or approved drug in the United States.[7]
Challenges and unanswered questions
There are legitimate reasons to regulate highly potent, concentrated, and chemically modified opioid compounds. It should also be noted that regulatory decisions have consequences for science. Schedule I status can make it substantially more difficult to obtain, store, administer, and study compounds in controlled laboratory settings. Current research surrounding kratom and its alkaloids has only started to uncover some answers to the potential therapeutic utility and side effect profiles.
Those questions cannot be answered by treating “kratom” as a single pharmacological entity, and this is why we examine the individual alkaloids. In recent work from my laboratory, we found that mitragynine reduced methamphetamine self-administration in rats without disrupting responding for food.[8] This study simply reported a biological finding and does not mean that mitragynine or kratom is a viable treatment for methamphetamine use disorder. It does demonstrate why the pharmacology deserves to be studied rather than reduced to a simple label of “good” or “bad.” Simply stated, we still have a lot to learn.
As the word ‘kratom’ becomes increasingly visible in the United States, the conversation needs to evolve. The public needs to be able to understand what is and is not being discussed. Those discussing kratom need to distinguish between a plant, its naturally occurring alkaloids, highly concentrated derivatives, and chemically modified compounds that can have very different pharmacological properties. Reducing all of these into one word, ‘kratom’ is misleading and potentially dangerous. The pharmacology matters.
Reference
[1]: https://nida.nih.gov/research-topics/kratom “Kratom | National Institute on Drug Abuse (NIDA) – NIH”
[2] Obeng S, Wilkerson JL, León F, Reeves ME, Restrepo LF, Gamez-Jimenez LR, Patel A, Pennington AE, Taylor VA, Ho NP, Braun T, Fortner JD, Crowley ML, Williamson MR, Pallares VLC, Mottinelli M, Lopera-Londoño C, McCurdy CR, McMahon LR, Hiranita T. Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for μ-Opioid Receptor and Opioid-Like Behavioral Effects in Rats. J Pharmacol Exp Ther. 2021 Mar;376(3):410-427. doi: 10.1124/jpet.120.000189. Epub 2020 Dec 31. Erratum in: J Pharmacol Exp Ther. 2022 Dec;383(3):250. doi: 10.1124/jpet.120.000189err. PMID: 33384303; PMCID: PMC7923387.
[3] Obeng S, Crowley ML, Mottinelli M, León F, Zuarth Gonzalez JD, Chen Y, Gamez-Jimenez LR, Restrepo LF, Ho NP, Patel A, Martins Rocha J, Alvarez MA, Thadisetti AM, Park CR, Pallares VLC, Milner MJ, Canal CE, Hampson AJ, McCurdy CR, McMahon LR, Wilkerson JL, Hiranita T. The Mitragyna speciosa (kratom) alkaloid mitragynine: Analysis of adrenergic α2 receptor activity in vitro and in vivo. Eur J Pharmacol. 2024 Oct 5;980:176863. doi: 10.1016/j.ejphar.2024.176863. Epub 2024 Jul 26. PMID: 39068978; PMCID: PMC11556301.
[4] León F, Obeng S, Mottinelli M, Chen Y, King TI, Berthold EC, Kamble SH, Restrepo LF, Patel A, Gamez-Jimenez LR, Lopera-Londoño C, Hiranita T, Sharma A, Hampson AJ, Canal CE, McMahon LR, McCurdy CR. Activity of Mitragyna speciosa (“Kratom”) Alkaloids at Serotonin Receptors. J Med Chem. 2021 Sep 23;64(18):13510-13523. doi: 10.1021/acs.jmedchem.1c00726. Epub 2021 Sep 1. PMID: 34467758; PMCID: PMC9235362.
[5] Zuarth Gonzalez JD, Ragsdale AK, Mukhopadhyay S, McCurdy CR, McMahon LR, Obeng S, Wilkerson JL. Mitragynine and 7-hydroxymitragynine: Bidirectional effects on breathing in rats. J Pharmacol Exp Ther. 2025 Nov;392(11):103720. doi: 10.1016/j.jpet.2025.103720. Epub 2025 Sep 22. PMID: 41106041; PMCID: PMC13169311.
[6]: https://www.fda.gov/news-events/press-announcements/fda-takes-steps-restrict-7-oh-opioid-products-threatening-american-consumers “FDA Takes Steps to Restrict 7-OH Opioid Products …”
[7]: https://www.fda.gov/news-events/public-health-focus/fda-and-kratom “FDA and Kratom”
[8] Khodavirdilou L, Gonzalez JDZ, Mukhopadhyay S, Guadagnoli N, Obeng S, McCurdy CR, McMahon LR, Wilkerson JL. Mitragynine reduces methamphetamine self-administration in rats without disrupting food-maintained responding. Psychopharmacology (Berl). 2026 Jul 10. doi: 10.1007/s00213-026-07124-6. Epub ahead of print. PMID: 42429925.
