In October, the Kratom Consumer Advisory Council released a position statement citing the top 10 reasons that kratom should not be grouped with isolated concentrated synthetic products as a public health concern.
“We are concerned that many members of the media, public, legislators and regulators are not distinguishing the historical natural kratom leaf product with these new products that bear little to no resemblance to the natural leaf,” the statement read. “We strongly believe that natural kratom leaf should be sensibly regulated and not banned.”
Originating from a tropical evergreen tree in the coffee family, kratom has been consumed by rural and agricultural communities in Southeast Asia for centuries—chewed or brewed as a mild stimulant, pain reliever and even natural remedy to ease opium addiction.
The alkaloid 7-hydroxymitragynine is not a natural constituent of kratom, which is present in trace amounts in the leaves post-harvest. In contrast, the concentrated, semi-synthetic 7-OH on the market is much more potent, man-made and interacts primarily with the same receptor system targeted by morphine, heroin and prescription opioids.
“7-OH is being sold as natural. It is not,” said Matthew Lowe, executive director of the Global Kratom Coalition, an advocacy group for the kratom industry. “It is being sold as kratom. It is not. It is being sold as a dietary ingredient or dietary supplement. It is not.”
Separating kratom from 7-OH
As one differentiator, the Kratom Consumer Advisory Council notes that the FDA has recommended that 7-OH—but not kratom leaf or its properly made extracts—be classified as a Schedule I controlled substance.
During a press conference in late July announcing the recommendation, FDA commissioner Marty Makary was also clear in distinguishing between the two.
“We’re not targeting the kratom leaf or ground-up kratom,” he said. “We are targeting a concentrated synthetic byproduct that is an opioid.”
This is not the first time a kratom compound has been on the chopping block. In 2016, the U.S. Drug Enforcement Administration (DEA) published a notice of intent to schedule, proposing to temporarily schedule kratom’s two alkaloids, mitragynine and 7-hydroxymitragynine, under the Controlled Substances Act. It stated that the uncontrolled distribution, importation and use of the compounds “pose an imminent hazard to the public safety”, citing 15 “kratom-related deaths” between 2014 and 2016.
Public outcry ensued, including a White House petition with nearly 140,000 signatures, opposition from nine U.S. senators and 51 members of the U.S. House of Representatives, and over 20,000 public comments from scientists, advocates and consumers in support of the kratom plant’s many uses. The agency withdrew the notice shortly thereafter, leaving the plant and its compounds unscheduled.
7-hydroxymitragynine is one of the main active alkaloids in kratom and is present in trace amounts in the leaves of the kratom plant. (@ Wirestock/ Getty Images)
Today kratom—sold in shops, cafés, supermarkets and online and often labeled as herbal or dietary supplement—is regularly consumed by just under 1% of Americans to address chronic pain, anxiety and depression, according to 2019 data from the National Survey on Drug Use and Health.
U.S. data on associated risks related to kratom only emerge with synthetics, not natural kratom leaf, according to the policy statement from the Kratom Consumer Advisory Council.
The FDA reported no serious adverse events from a “single-ascending dose” study of unprocessed kratom leaf in humans but views kratom as a “new dietary ingredient for which there is inadequate information to provide reasonable assurance that such ingredient does not present a significant or unreasonable risk of illness or injury.”
Kratom has also had to contend with prohibitions at the state level, with Louisiana becoming the seventh state to ban all kratom-based products and classifying them as Schedule 1 controlled substances in August.
“This is a tragic outcome of well-intentioned legislators who just overreact,” said Mac Haddow, senior fellow on public policy at American Kratom Association, an industry lobby group. “We’re working now with the governor’s office and with the legislatures to revise that policy for the next session coming up, because it needs to.”
If Louisiana repeals the ban, it would not be the first state to do so. Rhode Island repealed its 2025 kratom ban, reversing the policy with new legislation that goes into effect next year.
Currently, four U.S. states limit the concentration of 7-OH to no more than 2% of a kratom product’s total alkaloid composition under each state’s version of a Kratom Consumer Protection Act (KCPA). More than 20 states have some form of kratom regulation and 18 have their own version of a KCPA.
The American Medical Association recommends that those using kratom for pain management or other conditions “have access to appropriate medical care to manage their conditions and withdrawal symptoms, if needed.” It also recommends kratom be regulated by the FDA while ongoing clinical trials for safety and efficacy are completed before it is used for treatment.
“By definition, higher doses provide higher risks of any substance,” University of Florida kratom researcher Christopher McCurdy, PhD, PharmD, wrote on LinkedIn. “At some point, kratom extracts are harmful, yet we do not know scientifically where that level is.”
If alkaloid content demonstrates a high abuse potential, he said it should be considered for scheduling by the appropriate authorities.
“That is not up to scientists—scientists simply provide the data to inform those decisions,” Dr. McCurdy said. “Again, not all kratom products are equal. If scientifically we find a level of kratom extract that possesses an abuse liability, I would agree with scheduling those products, too.”
The initial influx and subsequent seizure of 7-OH
Kratom proponents have also been pushing for legal recognition at both the state and federal levels, partly in response to the influx of 7-OH and partly to prevent confusion between genuine kratom products and mislabeled products containing synthetic ingredients like 7-OH.
Over the last two years, 7-OH products have proliferated the market, with close to one million people using them per month, according to a report released by the Marwood Group, a healthcare-focused advisory and consulting firm. Millions of servings of 7-OH have been sold in the United States, which Holistic Alternative Recovery Trust (HART), a 7-OH lobby group, says validates product efficacy and use in addiction prevention. According to HART, four million U.S. consumers take the substance regularly.
The exact year when the first commercial 7‑OH product entered the market is not clearly documented, but Shaman Botanicals, LLC, a company that sells CBD-based items across the country, claims to be one of the first distributors.
In July, the company received an FDA warning letter, citing concerns that its products were adulterated and noting that there was “inadequate information to provide reasonable assurance that 7-OH does not present a significant or unreasonable risk of illness or injury.” The letter stated that “7-OH has been reported to have opioid-like effects” and “available information on the use of 7-OH in products raises serious safety concerns.” Similar warning letters were also sent to six other companies.
States have also taken actions to prohibit the sale of 7-OH products, with Texas and Mississippi either issuing a complete ban or limiting products with high concentrations of 7-OH. Florida issued an emergency rule that may represent the most stringent of state policies by classifying concentrated 7-OH products as a Schedule 1 controlled substance.
In September, further federal action included a coordinated effort by the FDA and the Bureau of Alcohol, Tobacco, Firearms and Explosives across several cities to seize 600,000 units of illegal products in smoke shops and convenience stores, including items containing 7-OH.
HART argues that the government’s battle against 7-OH is perpetuated by the kratom industry whose players are afraid of losing market share from competition.
“I’m not dumb. I understand capitalism,” said Jeff Smith, a former Missouri state senator turned national policy director for HART. “It’s been a very smart and brutally effective move by the other side to try to manufacturer a negative narrative in public health circles about 7-OH.”
The problem with 7-OH
Concerns about 7-OH go beyond potential side effects. Whereas the scientific study of kratom began in 1839, scientists are still trying to understand the chemical compounds that are created during 7-OH’s manufacturing process, including those unknown to chemistry and whether they have an impact on human health.
What scientists have found is that 7-OH can cause a number of side effects including respiratory depression. According to researchers like Dr. McCurdy, 7-OH products on the market are typically sublingual or chewable tablets, and most of the absorption happens rapidly in the mouth and likened to intravenous administration. If people are vaping it, 7-OH enters the blood supply, the lungs and goes straight to the brain, Dr. McCurdy said.
He added that with high enough doses, the semi-synthetic, concentrated 7-OH attaches to the mu-opioid receptor, the same one that most clinically prescribed opioids or illicit drugs like heroin bind to. 7-OH activates the receptor, which leads to pain relief and euphoric effects, but also can result in addiction, at least based on anecdotal evidence documented by University of Florida researchers.
Researchers worry that derivatives of 7-OH are leading to the creation of more potent compounds in the marketplace. (@ GIPhotoStock / Getty Images)
Dr. McCurdy, who receives partial funding from the Global Kratom Coalition, also noted that because 7-OH is manufactured in clandestine facilities not registered with or inspected by the FDA, the product often undergoes no purification to remove other chemicals formed during oxidation. The manufacturing process of 7-OH can involve using pool shock or high concentrations of chlorine.
“You’re dealing with a product that it is being used for certain benefits and drug-like claims that have not been evaluated or approved by the FDA,” McCurdy added, emphasizing that public health is about protecting eminent dangers to society.
Paula Brown, PhD, director of applied research, natural health and food products at the British Columbia Institute of Technology, agrees and has tested 7-OH products. She has found that they contain “very high levels” of 7-hydroximitragynine, demonstrating an “alarming lack of control in manufacturing.”
Brown said 7-OH manufacturers are also labeling these products as “kratom extracts” which is false and misleading, exposing unknowing consumers who believe they are receiving traditional kratom products but instead are being exposed to unapproved drugs with abuse liability potential and unknown risks.
Meanwhile, in support of 7-OH, a coalition of veterans who use 7-OH for pain management, recently penned a letter to Health and Human Services Secretary Robert F. Kennedy, Jr. to urge the Trump administration not to outlaw the substance before research on its safety and benefits is complete.
Confirming cause of death
While the 2016 notice of scheduling attributed 15 deaths to kratom compounds, the cause of death may not always be so easy to determine.
To date, reports indicate that many fatalities associated with kratom use primarily involve polydrug exposures, according to research from San Diego State University/University of California San Diego and the National Institute on Drug Abuse Intramural Research Program. Reported side effects appear to be dose-dependent and are more commonly observed at doses exceeding 8 grams.
Centers for Disease Control data collected from the State Unintentional Drug Overdose Reporting System (SUDORS) shows that between 2016 to 2017, only seven decedents tested positive for kratom in their systems of the more than 27,000 overdose deaths reported during that period.
Determining whether deaths are attributable to kratom or 7-OH products can be difficult because toxicology analysis often only tests for mitragynine, which appears in products containing either substance.
“There’s still a lot of confusion amongst the public, amongst healthcare providers that these semi-synthetic products are lumped into that same bucket as all kratom products,” Dr. McCurdy said. “There’s not a real strong effort that’s been made to separate those.”
In a recent editorial, Jeffrey A. Singer, MD, a senior fellow at the Cato Institute, argued that in cases where coroners have identified 7-OH in overdose deaths, victims had many other drugs in their system, including fentanyl and cocaine.
Toxicology tests do exist to differentiate kratom and 7-OH to help decipher which death is related to which substance, but not all forensic laboratories have access to those.
Notwithstanding, an FDA Center for Drug Evaluation and Research toxicology report indicates that “the number of fatal overdose cases in which one or more of these substances were detected for 2023 to 2025 are approximately three-fold higher than for the years 2019 through 2022, coinciding with the more recent entry of more-concerning kratom-related products in the marketplace, such as 7-OH.”
7-OH advocates offer an alternative narrative and say that drug-related deaths overall have dropped in part due to the availability of 7-OH. They say it is a substitute for other, highly addictive opioids.
“If 7-OH posed the kind of urgent danger that would justify emergency action, evidence would have been presented—it was not,” HART’s Smith said. “When a reporter [at the FDA press conference] asked if the government could attribute even a single death to 7-OH, no official was able to do so… Health and Human Services also claimed there is an epidemic of people dying from it. Where is the data showing this?”
In a press release by HART, Edward Boyer, MD, PhD, professor of emergency medicine at Ohio State University, reviewed nationwide toxicology databases, including poison center data and found limited evidence of acute overdose risk from 7-OH.
“Based upon data available at this time, given the degree of population exposure, the lack of findings suggests that 7-hydroxymitragynine carries no unreasonable risk of overdose death,” Dr. Boyer noted.
Kirsten Smith, PhD, an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University who is studying kratom’s effects in humans, has said that there is not really a “public health signal” of adverse events for either kratom or for 7-OH. She expressed her surprise that 7-OH was pushed for scheduling without data to support it.
A federal ban may encourage the drug cartels to sell 7-OH, Dr. Singer warns. He argues the cartels would welcome the opportunity to produce and smuggle 7‑OH to recoup their lost market share in the marijuana trade.
Dr. McCurdy said there may even be more pressing, homegrown risks to public health beyond 7-OH in its present form.
While recent federal and state actions move to restrict 7-OH, manufacturers are creating new compounds from it, like MGM-15 and MGM-16, that are more potent than 7-OH and already on the market. There is currently no preclinical research for those compounds to determine safety, as there were for 7-OH. Dr. McCurdy said he and his colleagues are trying to “frantically” conduct studies.
“You’re going to have these synthetic compounds out there,” he said. “Even a vendor told me that they weren’t worried [about legislation] because they have the next two or three things lined up after 7-OH. It’s kind of frightening.”