Background

                  Kratom has gained popularity over recent years due to its widespread availability as an over-the-counter nootropic agent. Kratom products are derived from the leaves of the mitragyna speciosa tree native to Southeast Asia¹. Kratom is often marketed as a dietary supplement, mood enhancer, or pain reliever, and is available to purchase in gas stations, smoke shops and from online retailers¹.

                  Recently, more potent kratom byproducts have been introduced into the U.S. market. 7-hydroxymitragynine (7-OH) and pseudoindoxyl mitragynine (MP), are semi-synthetic derivatives of mitragynine, the main alkaloid found in kratom². Mitragynine acts as an atypical opioid agonist and is primarily responsible for producing kratom’s psychoactive effects².

               Increasing concerns have arisen regarding the safety of kratom and similar products, due to their high potential for misuse and misleading labeling². The FDA has taken steps to restrict the sale of 7-OH and has pushed for its scheduling under the Controlled Substances Act³. Due to the potential risks associated with the use of these products, there is a call for increased awareness and education for consumers.

Mechanism

               Mitragynine is the most abundant alkaloid, among 50 other alkaloids, present in kratom⁴. It is considered a partial opioid agonist, weakly acting on the μ-opioid receptor⁴. Mitragynine has several other mechanisms of action in the brain, including effects on serotonergic, adrenergic, delta and kappa opioid receptors⁴. Mitragynine is credited for producing the analgesic effects associated with kratom⁴.

               7-Hydroxymitragynine, or 7-OH, is a mitragynine metabolite that is converted from mitragynine in the liver². 7-OH has a significantly higher potency than its parent metabolite and has been shown to have higher abuse potential⁵. According to researchers, 7-OH is 22-fold more potent than mitragynine as a μ-opioid receptor agonist⁵. 7-OH is then further converted to mitragynine pseudoindoxyl (MP) in human plasma, producing a chemical even more potent than 7-OH, and nearly as potent as fentanyl².

Effects

                  Individuals report using kratom and similar products to treat several conditions including headaches, diarrhea, insomnia and anxiety². There are also reported cases of individuals using these products to self-treat symptoms related to opioid use disorder (OUD)⁶. Kratom, 7-OH and MP containing products can cause effects that mimic classical opioids, such as morphine, fentanyl, oxycodone, and hydrocodone³. Use of these products can also lead to adverse effects including liver toxicity, seizures and substance use disorder (SUD)¹. Research shows there is also a significant risk of respiratory depression associated with 7-OH, similar to that of morphine⁴.

Treatment

                 Prolonged use of kratom, 7-OH, and MP containing products can result in increased tolerance, dependance and withdrawal when stopping use abruptly⁶. In the event of a suspected 7-OH involved overdose, it is recommended to use naloxone to reverse the effects⁵. Several studies have showed success in treating kratom dependence and withdrawal with buprenorphine^6,7,8 however there are currently no standard guidelines for treating OUD induced by kratom use⁷. There are case reports of 7-OH mitragynine use specifically requiring medically managed withdrawal with buprenorphine⁸.

Conclusion

                 U.S. Poison Centers have reported multiple cases of 7-OH exposure resulting in serious adverse outcomes this year⁴. However, the number of adverse events related to 7-OH is likely to be underreported due in part to a lack of self-reporting among individuals who may not be aware of the presence of 7-OH in some kratom products⁴. Additionally, the National Poison Data System codes for reporting cases of 7-OH exposure were only added earlier this year⁴.

                 According to FDA reports, a major concern regarding these products is misleading labeling and false claims by manufacturers¹. Since neither 7-OH or MP are naturally occurring in the dried leaves of the kratom plant, researchers believe that semi-synthetically produced 7-OH and MP formulations are being added to products². 7-OH and MP products are sometimes misleadingly marketed as kratom, leading to consumers obtaining products containing high-potency synthetic substances, rather than a natural botanical⁴.

                 The use of these products poses a threat to public health, necessitating a need for awareness among consumers and the public. To learn more about Kratom and other contaminants, visit the MATTERS website at https://mattersnetwork.org/edu/.

References

1. Commissioner O of the. FDA and Kratom. U.S. Food and Drug Administration. Accessed August 27, 2025. https://www.fda.gov/news-events/public-health-focus/fda-and-kratom.
2. Hill K, Smith KE, Grundmann O, Boyer EW. De facto opioids: Characterization of novel 7-hydroxymitragynine and mitragynine pseudoindoxyl product marketing. International Society of Addiction Journal Editors. May 8, 2025. https://www.sciencedirect.com/science/article/pii/S0376871625001541.
3. Commissioner O of the. FDA takes steps to restrict 7-oh opioid products threatening American consumers. U.S. Food and Drug Administration. Accessed August 27, 2025. https://www.fda.gov/news-events/press-announcements/fda-takes-steps-restrict-7-oh-opioid-products-threatening-american-consumers.
4. 7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat. United States Food and Drug Administration. Accessed August 26, 2025. https://www.fda.gov/files/drugs/published/7-hydroxymitragynin_7-oh_an_assessment_of_the_scientific_data_and_toxicological_concerns_around_an_emerging_opioid_threat.pdf
5. Kamble SH, León F, King TI, et al. Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy. ACS Pharmacol Transl Sci.2020;3(6):1063-1068. Published 2020 Jul 31. doi:10.1021/acsptsci.0c00075
6. Khazaeli, Azin MD; Jerry, Jason M. MD; Vazirian, Mohsen MD. Treatment of Kratom Withdrawal and Addiction With Buprenorphine. Journal of Addiction Medicine 12(6):p 493-495, November/December 2018. | DOI: 10.1097/ADM.0000000000000435.
7. Weiss, Stephanie T. MD, PhD; Douglas, Heather E. MD. Treatment of Kratom Withdrawal and Dependence With Buprenorphine/Naloxone: A Case Series and Systematic Literature Review. Journal of Addiction Medicine 15(2):p 167-172, March/April 2021. | DOI: 10.1097/ADM.0000000000000721.
8. Wightman, Rachel S. MD; Hu, David MD. A Case of 7-OH Mitragynine Use Requiring Inpatient Medically Managed Withdrawal. Journal of Addiction Medicine, 10.1097/ADM.0000000000001558, August 4, 2025. | DOI: 10.1097/ADM.0000000000001558.