KRATOM PRODUCTS VS 7-HYDROXYMITRAGYNINE (7-OH): UNDERSTANDING THE DIFFERENCE

Debate over kratom has long centered on the same concept: Despite changes in science and public policy, it’s been a back-and-forth between “good” responsible kratom producers and the “bad actors” that have drawn the ire of legislators and law enforcement. 

Many factors have fueled this debate, but this past year has distilled it down to one recurring theme. 

At the heart of the debate are two of the alkaloids found in the kratom plant: mitragynine, the primary alkaloid associated with natural kratom, and 7-hydroxymitragynine (7-OH), a metabolite that is only found in trace amounts in natural kratom leaves. The difference in those alkaloids has shown up in laws regulating kratom products, online debates and, most recently, a renewed attempt by the FDA to target 7-OH as the dangerous element in what the public perceives as natural kratom products. As the science and laws around kratom develop, consumers and advocates for the plant are becoming aware of a fact that scientists have been fixated on for years–natural-based kratom products are NOT the same as 7-OH products. 

Studying the Science

Starting with the basic science of the two alkaloids, there are distinct differences between mitragynine and 7-OH. Mitragynine is the most abundant alkaloid found in the kratom plant (scientifically known as Mitragyna speciosa), and is the primary psychoactive element of traditional kratom products. In Indonesia, where kratom has documented uses dating back centuries, kratom leaves are brewed into beverages that rely almost exclusively on mitragynine to provide a daily boost to laborers and other workers. 

But when the Western world began exporting kratom for use beyond its natural habitat, 7-OH became more of a presence in the scientific profile of products associated with the plant. 

Researchers refer to 7-OH as a “decay metabolite”, meaning it becomes more pronounced in the plant as the leaves dry out during shipping and processing. Even as the leaves dry, the amount of 7-OH found in natural kratom products is still hardly comparable to the amount of mitragynine. 

That means that to get enough 7-OH, these “enhanced” products are made using chemically synthesized or semi-synthesized alkaloids. As part of his appearance on “The Huberman Lab” podcast, Dr. Christopher McCurdy explained that the producers of 7-OH products can purchase purified mitragynine from international labs to aid in this process. 

David Kroll, a professor and the director at the University of Colorado’s Anschutz Skaggs School of Pharmacy and Pharmaceutical Sciences, explained the process further in a news release. 

“What happens is there's not enough 7-OH in the leaf to economically purify it away from everything else. Companies have purified mitragynine, which can be bought in bulk in kilograms,” Kroll said. “Then, in the laboratory, they put the hydroxyl group on the seven position to make 7-OH. In chemistry, we would call it semi-synthetic, meaning it starts with a natural compound, and then we partially synthesize the 7-OH version.” 

Why it Matters to Consumers

As part of that news release, Kroll stated that 7-OH products are “five-to-50-fold more potent on the brain than mitragynine as an opioid receptor agonist” once it has been chemically processed to become the primary alkaloid in a product. 

Due to that process of chemically altering natural kratom leaves into a new compound, McCurdy has made it clear through his academic research and publications that 7-OH is NOT kratom, and that the risk posed by this new substance far exceeds any concern associated with the natural kratom leaf. 

Alongside researchers at Johns Hopkins and Ohio State University, McCurdy was part of a panel that testified before Congress to update the federal government, and the key component of McCurdy’s portion centered on a comparison of natural leaf kratom products to products with elevated levels of 7-OH. It was presented as a bar graph of alkaloids and highlighted the lack of measurable amounts of 7-OH in the leaf products. 

“We have fingerprinted what the alkaloid profile looks like in the native leaf, and most products, including extracts, meet this fingerprint,” McCurdy said. “7-hydroxy is not present in leaf materials.” 

Beyond the lack of 7-OH in natural kratom leaf products, McCurdy also highlighted that the way some producers are synthesizing 7-OH is actually adding in unknown elements to the chemical profile of the commercial products that were tested in his laboratory. Although mitragynine was still the most abundant alkaloid in the 7-OH products shown, many risk factors simply are not present in the chemical profile of natural kratom leaf. 

“This is synthetically created from a mitragynine isolate concentrate. There are several compounds in that tablet that we have no idea what they are. We have no idea what the harm could be or the risk, or what’s there,” McCurdy said.

Furthermore, McCurdy has also done animal studies on 7-OH that back Kroll’s statements: When it comes to effects on opioid receptors in the brain, 7-OH is a completely different product than natural leaf kratom. As more producers have begun removing mitragynine and selling products that are almost entirely made up of 7-OH alkaloids, McCurdy and his peers began sounding the alarm. 

“This is concerning for all of us as scientists because this product is making a huge impact in the marketplace right now, and it is not kratom,” McCurdy said. “This is something that needs the attention of authorities.” 

It took nearly a year for the authorities to get the message, but eventually the points raised by McCurdy and his peers at that briefing led to action from the Food and Drug Administration in July of this year. At a press conference hosted by the FDA, top officials from the agency made the case against 7-OH products and announced an effort to label 7-OH a Schedule I substance at the federal level. More importantly, for the first time, the FDA made a clear distinction between natural kratom products and 7-OH. 

It may have taken longer than what the experts were hoping for, but it can be summed up by the bar graphs presented by McCurdy, which clearly illustrated the chemical manipulation by producers who artificially enhance their products. 

“Anybody, including someone who watches Sesame Street's 'Which One is Different, ' can definitely see that the one on the right is totally different than the one on the left,” McCurdy said.