Kratom and the Impact of 7-OH Reclassification

Mitragyna speciosa or kratom leaves with medicinal products in capsules and powder in white ceramic bowl and wooden table, top view | Image Credit: ©Yanawut Suntornkij - stock.adobe.com

On July 29, 2025, FDA published recommendations for the control of concentrated 7-hydroxymitragynine (7-OH) products under the Controlled Substances Act (1), because a concentrated byproduct of the kratom plant has been recognized as having the potential for abuse due to its ability to bind to opioid receptors. The agency also released a report, “7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat,” detailing concerns over these products. FDA’s recommendations now go to the Drug Enforcement Agency, which has authority over drug classification.

On Aug. 14, 2025, Florida Attorney General James Uthmeier issued an emergency rule filing to classify certain 7-OH products as Schedule 1 controlled substances in Florida. The rule makes it illegal to sell, possess, or distribute certain 7-OH drugs in the state (2).

Pharmaceutical Technology® interviewed C. Michael White, distinguished professor and Chair of the Department of Pharmacy Practice at the UConn School of Pharmacy and chair of the Kratom Consumer Advisory Council, to find out how these regulatory actions may impact the pharmaceutical industry and consumers.

Kratom and opioids

PharmTech: Can you please explain what kratom is and how it is used in the development of opioids?

White: There is a Mitragyna speciosa tree in Southeast Asia that was called kratom by indigenous people when Western explorers arrived in the 1800s. The leaves contain many phytochemical alkaloids that can act on receptors in the body. Mitragynine is the most abundant alkaloid and stimulates serotonin, alpha-1 and alpha-2 adrenoceptors, and indirectly and mildly stimulates opioid receptors. Mitragynine is a unique opioid receptor stimulator because it is a mild stimulator rather than a depressant and is unlikely to cause reductions in respiratory rate or minute ventilation as the dose escalates. One of the metabolites of mitragynine is 7-OH, which is a very potent but short-acting opioid receptor stimulator, and the metabolite of 7-OH is mitragynine pseudoindoxyl, which is also a potent opioid receptor stimulator but possibly with a longer duration of action.

Instead of following the normal process where chemicals derived from natural products are pre-clinically tested to support an IND [investigational new drug] application followed by Phase I, II, and III clinical trials, manufacturers simply extracted mitragynine, oxidized it to make 7-OH, and then chemically converted it to make mitragynine pseudoindoxyl. [They] started putting it into products and selling it to consumers with no involvement of health professionals.

Consumers could self-select if they wanted to take it, even if it was just to experience euphoria, choose the duration of therapy, and choose their own dose. This seems to be against FDA’s drug approval process and sets a horrible precedent for drug development. These products were never approved as new dietary ingredients and should not have been legally sold as dietary supplements, but they were.

While 7-OH is found in trace amounts (less than 2% of total alkaloids) in the dried kratom powder, it is not in the fresh leaf, so whether it would qualify as a dietary supplement is unclear. However, it is clear that mitragynine pseudoindoxyl is not found in fresh or dried kratom leaves and should never be allowed as a dietary supplement.

[This situation] is similar to the recent sales of tianeptine as a dietary supplement. Tianeptine is a fully synthetic molecule and used as a drug in some European countries but appeared on gas station, convenience store, and smoke shop shelves as a dietary supplement. This exposes a major vulnerability in our drug and dietary supplement market where dietary supplements do not need to notify FDA before they are sold, and it is up to the overworked and understaffed FDA to discover them and then start testing, warning, and enforcement actions. Additionally, 7-OH products are actually being sold in vape pens, sublingual strips, and buccal pouches even though dietary supplements can only be swallowed. This is blatant disregarding of federal law.

Reclassification of 7-OH products

PharmTech: How do the recommendations by FDA, and Florida’s emergency ruling to reclass certain concentration 7-OH opioids as controlled substances, impact the pharmaceutical industry, patients, and consumers?

White: The actions from FDA and [the] Florida Attorney General are desperately needed by the pharmaceutical industry, patients, and consumers. Pharmaceutical companies following FDA guidance and spending billions of dollars to bring a drug to market that is proven to have a positive benefit-to-risk profile in human clinical trials should not be competing against competitors that are circumventing the process and directly reaching consumers. Patients are being denied access to well-tested, novel drugs because prescribers cannot be certain if the risks of these new products are better or worse than current options, how to use the drugs in unique patient types, and what the risk of drug interactions are. Consumers are taking products that animal studies show are highly addictive with no protections. Many of the products are being sold next to the Gatorade and Mentos and are fruit-flavored, sugar-enhanced candy formulations with names that would appeal to children or drug seekers.

PharmTech: What actions will pharmaceutical companies need to take to respond to the new regulations?

White: I hope that pharmaceutical companies would become more aware of competitors that are cutting corners and directly reaching consumers with their drug products or are selling dietary supplements in ways that are clearly illegal but compete with prescription products (like natural GLP-1s given in transdermal patches). These are not counterfeit drug makers, which pharmaceutical companies are adept at combatting; but companies selling products for the same indications but are unique chemical entities, or are using legal loopholes like saying they are ‘peptide’ companies to sell counterfeit versions of drugs to consumers, pretending that they are only selling them for ‘research purposes.’ Another great example is people selling THC [tetrahydrocannabinol], used to help people sleep, reduce stress, etc., but use a loophole in the Farm Bill to create THC and THC-like chemicals from extracts of ‘hemp’ cannabis plants. FDA does not have the bandwidth to combat these entities unless this type of enforcement becomes prioritized.

References

1. FDA. FDA Takes Steps to Restrict 7-OH Opioid Products Threatening American Consumers. Press Release. July 29, 2025. https://www.fda.gov/news-events/press-announcements/fda-takes-steps-restrict-7-oh-opioid-products-threatening-american-consumers
2. Makary, M.A. Statement from FDA Commissioner Marty Makary, MD, MPH, on Florida Restriction of 7-OH Opioid Products. FDA.gov. Aug. 13, 2025. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-marty-makary-md-mph-florida-restriction-7-oh-opioid-products