Kratom groups, researchers sound alarm over 7-hydroxymitragynine products

This past May in Atlantic City, New Jersey, at a business-to-business trade expo for the smoke shop industry, Todd Underwood was talking to a man who had just tried a product containing 7-hydroxymitragynine (7-OH), a compound associated with the botanical kratom.

According to Underwood, whose beverage company MitWellness sells products containing kratom (Mitragyna speciosa) and kava (Piper methysticum), the man attending the CHAMPS B2B event went to an emergency room after mentioning he had tried 7-OH for the first time, couldn’t breathe and felt like he was losing consciousness.

“We already have an opioid crisis,” Underwood said, cautioning the U.S. market is being flooded with 7-OH tablets that pose a risk to public health. 7-OH “is highly addictive. Somebody’s going to die.”

Now, a group of prominent kratom researchers in the U.S. is sounding the alarm over 7-OH and mitragynine pseudoindoxyl (formed in the human body from 7-OH after metabolism of mitragynine) products. On Tuesday, June 11, four academics from the University of Florida College of Pharmacy and Johns Hopkins University School of Medicine noted that 7-OH and mitragynine pseudoindoxyl are not present in native kratom leaf material. A product with high amounts of these compounds contains an isolated, purified or semi-synthetically generated form of 7-OH and/or mitragynine pseudoindoxyl, according to their public statement.

Related:Is kratom a safe life-giver or a dangerous life-taker?

“Such products should not be scientifically considered or commercially categorized as kratom or as a kratom product,” the researchers wrote. They added, such claims are not credible or factual and a product containing high amounts of the aforementioned compounds is subject to FDA drug approval based on the Federal Food, Drug and Cosmetic Act (FDCA).

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A few months ago, on the social forum Reddit, one person expressed concern that 7-hydroxymitragynine “will be tianeptine for me over again.” Tianeptine, nicknamed "gas station heroin," has drawn public health concerns from FDA. The agency has warned it has received reports of severe adverse events connected to tianeptine, including death, loss of consciousness and seizures.

Another Reddit user described 7-OH as “f*ckin amazing,” adding “kratom has a pretty low ceiling for effects but with 7 hydroxy you can get rlly [sic] up there without getting nauseous or wobbly.”

“Be careful. Be super careful,” someone else on the Reddit thread warned. “I had to go to detox to get off it. The withdrawals are insane.”

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Professor Christopher McCurdy, Ph.D., is a medicinal chemist, behavioral pharmacologist and pharmacist at the University of Florida College of Pharmacy. He said 7-hydroxymitragynine has been studied in dogs, mice and rats for pharmacokinetics, and researched in mice and rats for pain relief and abuse potential.

Related:Kratom proponents make progress in overturning Rhode Island ban

McCurdy, one of the four kratom experts to issue the public statement, described 7-OH as “a pure opioid compound” that only interacts with opioid receptors. Mu-opioid receptors (MOR) affect such physiological factors as endocrine activity, mood, memory, respiration and stress, according to an article published in StatPearls, a health care education and tech company.

7-OH “is more selective for opioid receptors than many of the traditional opioids,” McCurdy told Natural Products Insider in an email. “It has shown to substitute for morphine in rats that have been trained to self-administer morphine, and it also shows a ‘denovo’ ability to become self-administered by rats, whereas mitragynine did not show this ability. Therefore, it is extremely likely that 7-OH is physically and psychologically addictive with high potential for abuse. In short, when isolated or heavily concentrated, it should be a controlled substance.”

Kratom researcher Kirsten Elin Smith, Ph.D., is an assistant professor in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine.

Related:FDA, states mount war on Kratom

Smith, who is also among the four experts to issue the joint statement, characterized 7-OH “as a very selective mu-opioid receptor agonist” with “greater binding affinity than mitragynine.” According to FDA, mitragynine and 7-hydroxymitragynine are the two main chemical compounds in kratom.

Using a love or romance analogy, Smith explained that mitragynine “is “attracted to the mu-opioid receptor but only to a point.”

By comparison, 7-hydroxymitragynine is “in love with the receptor,” she said in an interview. “It’s very selective for it. It doesn’t have eyes for others.”

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In January 2024, at the CHAMPS expo in Las Vegas — described as “the premier counterculture B2B expo since 1999" — only two companies were selling 7-OH, according to Underwood. Several months later at the recent CHAMPS expo in Chicago (where MitWellness had a booth), the number of companies selling 7-hydroxymitragynine had swelled to 37, he reported.

Todd Underwood, president and CEO of MitWellness, said the U.S. market is teeming with 7-OH products that pose a risk to public health.

Smith said 7-hydroxymitragynine does not appear in the kratom leaf material at an amount that can be quantified. She described the compound as an “active metabolite” that may be detected at extremely low levels in the plant material after it is harvested and, for example, exposed to sunlight.

According to Underwood, the products are synthetically created in a lab “and the FDA says, ‘Hey, if you want to create a new drug, here’s how you do it.'"

“FDA should be stopping those companies from manufacturing new drugs and releasing those through vape and smoke shops,” he asserted. “It’s putting the public at risk and the FDA knows about it, and they’ve done nothing.”

Underwood and the kratom researchers are not the only ones to raise concerns about 7-OH. At least two groups have issued statements in recent months: the American Kratom Association (AKA) and Global Kratom Coalition (GKC).

Mac Haddow, senior fellow on public policy with the AKA, said products containing concentrated amounts of 7-OH are not legitimate kratom products and should be labeled to contain a disclaimer that they could be highly addictive.

In an April 16 statement, the AKA advised consumers to not buy “any enhanced 7-OH product because they pose a real safety threat to anyone who consumes” them.

One of the concerns with high dosages of 7-OH is the unknown health implications, according to Matthew Lowe, executive director of the GKC. He raised another concern: the prospect that a naïve consumer wanting to try kratom is given something entirely different.

The consumer “can easily be given a 7-OH product disguised as kratom as opposed to starting off with leaf, which we understand,” Lowe said in an interview. “We understand the safety profile [of kratom leaf], and it’s relatively innocuous in comparison.”

7-HYDROXYMITRAGYNINE IS “IN LOVE WITH THE [MU-OPIOID] RECEPTOR. IT’S VERY SELECTIVE FOR IT. IT DOESN’T HAVE EYES FOR OTHERS.”

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Kratom can produce effects similar to stimulants and opioids, and people report using it to manage cravings (particularly related to opioid use) and drug withdrawal symptoms, as well as pain, fatigue and mental health problems, according to the National Institute on Drug Abuse (NIDA).

NIDA noted rare though serious effects — including cardiovascular, gastrointestinal (GI), respiratory and psychiatric problems — have been reported in individuals who use kratom.

“Compared to deaths from other drugs, a very small number of deaths have been linked to kratom products, and nearly all cases involved other drugs or contaminants,” NIDA added in a webpage on kratom.

A spokesperson for NIDA referred questions about 7-OH to the Food and Drug Administration. FDA’s Center for Drug Evaluation and Research (CDER) issued a generic statement to Natural Products Insider in response to an inquiry regarding the concerns expressed by the kratom groups.

CDER described 7-hydroxymitragynine as “a compound found in some kratom products (in varying amounts).”

“The FDA makes regulatory decisions based on available science,” CDER said in a June 6 email, five days before the kratom researchers issued their joint statement. “The agency continues to evaluate the available safety information about the effects of kratom and associated compounds, including the alkaloid compounds mitragynine and 7-hydroxymitragynine. We continue to encourage health care professionals and consumers to report any adverse reactions to the FDA’s MedWatch program.”

University of Florida Professor Christopher McCurdy, Ph.D., said 7-hydroxymitragynine “is more selective for opioid receptors than many of the traditional opioids.”

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Three months ago on Reddit, a person described 7-OH as “the cleanest and more euphoric high that I’ve gotten from taken [sic] any kratom shots or powders.”

“This sh*t if all goes well will completely take over the kratom market. Watch!” they added.

Commenting on the post above, another individual warned that 7-OH “can be deadly” and is “a slippery slope.”

The marketplace has “strayed very far away from what nature was producing,” and as is the case with cannabinoids, 7-OH products resemble more of a drug than a botanical or dietary supplement, Smith concluded.

Products containing high or synthetic levels of 7-OH “are starting to look less like kratom and more like an opioid,” she added.

McCurdy warned 7-OH isolates or concentrated products are made using dangerous chemical oxidants that are also producing side products that could be even more hazardous.

“These products should be removed from the market,” he contended. “If they are not, since they are considered ‘kratom,’ it puts the entire kratom marketplace at risk for being banned and removing all kratom from access to those that use it responsibly.”