FDA Seeks Scheduling Action to Control Harmful Kratom Plant Byproduct

A concentrated byproduct of the kratom plant that is being increasingly recognized as having the potential for abuse, due to its ability to bind opioid receptors, is FDA’s latest target under the Controlled Substances Act (CSA) (1).

7-hydroxymitragynine (7-OH) products are the subject of FDA’s new recommendation of a scheduling action to control such products under the CSA (1). FDA has released a report, “7-Hydroxymitragynine (7-OH): An Assessment of the Scientific Data and Toxicological Concerns Around an Emerging Opioid Threat,” available for PDF download on the agency’s website, to educate the public.

Kratom and 7-OH: the same, but different

The chief distinction FDA said it would like to make, according to a July 29, 2025, press release, is that 7-OH and the kratom plant leaf are not analogous. However, while no 7-OH drugs have been approved by FDA and it is not lawful in dietary supplements or to be added to conventional foods, kratom itself is also not lawfully marketed in the United States as a drug product, dietary supplement, or food additive (1,2).

Yet, in 2021, FDA said approximately 1.7 million Americans aged 12 and older used products prepared from the leaves of the kratom—or Mitragyna speciosa, a tropical tree native to Southeast Asia—to self-treat numerous conditions, including pain, coughing, diarrhea, anxiety, and depression (2).

Products marketed to children

It is also used to self-medicate against opioid use disorder and opioid withdrawal, but it is in these cases, FDA said, in which the use of 7-OH can be concerning. In June, the agency issued warning letters to seven companies for the illegal distribution of 7-OH products that included tablets, gummies, drink mixes, and shots (1). There is concern about a festering market of products that may appeal specifically to children and teenagers, such as fruit-flavored gummies and ice cream cones.

Broader advisements were issued July 29 to healthcare professionals and consumers by FDA Commissioner Marty Makary, MD.

Worse than morphine?

“Vape stores are popping up in every neighborhood in America, and many are selling addictive products like concentrated 7-OH,” Makary said in the FDA press release (1). “After the last wave of the opioid epidemic, we cannot get caught flat-footed again. 7-OH is an opioid that can be more potent than morphine [13 times more, according to a 2002 study in the Journal of Medicinal Chemistry (3)]. We need regulation and public education to prevent another wave of the opioid epidemic.”

Under the terms of the Controlled Substances Act, drugs and other certain chemicals are placed into one of five schedules based on medical use, potential for abuse, and safety or dependence liability (1). The Drug Enforcement Administration (DEA), which has final scheduling authority, is reviewing FDA’s recommendation on 7-OH; a public comment period must precede any action being ultimately taken.

FDA in focus

FDA’s crackdown on 7-OH is just the latest in a flurry of policy and personnel shifts at the agency. In July alone, a new director of the Center for Drug Evaluation and Research (CDER), George Francis Tidmarsh, MD, PhD, was appointed, while Center for Biologics Evaluation and Research Director Vinay Prasad, MD, suddenly departed the organization after less than three months on the job (4,5).

Prasad’s exit came on the heels of FDA’s showdown with Sarepta Therapeutics over Elevidys, an FDA-approved gene therapy for patients with Duchenne muscular dystrophy. Under pressure from the agency and in the aftermath of at least three deaths, including children, Sarepta paused distribution of the treatment in the United States on July 21 (6).

As for CDER, that department under Tidmarsh’s leadership published a whitepaper on July 29 that articulates how investments in mature quality management practices can offer measurable returns, both economically and in terms of public health (7). The paper argues that these practices enhance public health by stabilizing supply chains and preventing drug shortages, crucial during high-demand periods like the COVID-19 pandemic.

What developments mean for biopharma

On July 10, FDA made public more than 200 Complete Response Letters (CRLs) written between 2020 and 2024 regarding drug and biologic applications that were not approved during their initial review cycle (8). Pharmaceutical Technology® Group then delved into a CRL made public on July 22, exploring the underlying issues in these letters that frequently involve chemistry, manufacturing, and control maturity, manufacturing consistency, and analytical validation, even for sponsors with strong FDA engagement throughout development (9).

Within this prism of transparency, there are implications from FDA’s targeting of 7-OH that are industry-wide. Developers exploring kratom-based therapeutics are being urged to be cautious. Enhanced 7-OH products—often synthetically derived—raise concerns over abuse liability and may face future regulatory scheduling, impacting both clinical research and investigational drug approval pathways.

Marketed kratom products also frequently contain unnaturally high levels of 7-OH due to chemical alteration. These adulterated formulations present challenges for pharmaceutical manufacturers around ingredient sourcing, product consistency, and compliance with FDA regulations on unapproved drug substances.

Finally, surveillance data from poison centers, DEA testing, and social media point to rising 7-OH exposures and adverse events. FDA warns of regulatory gaps enabling OTC and online sales of high-dose 7-OH products, urging immediate policy responses to mitigate the growing public health risk.

References

1. FDA. FDA Takes Steps to Restrict 7-OH Opioid Products Threatening American Consumers. Press Release. July 29, 2025.
2. FDA. FDA and Kratom. FDA.gov, last updated July 29, 2025 (accessed July 30, 2025).
3. Takayama, H.; Ishikawa, H.; Kurihara, M.; et al. Studies on the Synthesis and Opioid Agonistic Activities of Mitragynine-Related Indole Alkaloids: Discovery of Opioid Agonists Structurally Different from Other Opioid Ligands. J. Med. Chem. 2002, 45 (9) 1949–1956. DOI: 10.1021/jm010576e
4. FDA. Stanford Faculty Member George Tidmarsh, MD, PhD Named Director of Center for Drug Evaluation and Research. Press Release. July 21, 2025.
5. Cole, C. FDA Shake-Up: Vinay Prasad Exits Amid Tumult in Biologics Oversight. PharmTech.com, July 30, 2025.
6. Lavery, P. FDA Investigates Pediatric Elevidys Death: 5 Things to Know. BioPharmInternational.com, July 28, 2025.
7. Lavery, P. 3 Reasons FDA Says Quality Investments Are Essential for Drug Manufacturers and Patients. PharmTech.com, July 29, 2025.
8. FDA. FDA Embraces Radical Transparency by Publishing Complete Response Letters. Press Release. July 10, 2025.
9. Cole, C. Manufacturing and CMC Challenges in Immunotherapy: Lessons from Recent Complete Response Letters. BioPharmInternational.com, July 25, 2025.