What Is 7-OH, and Why Is It Being Targeted in Kratom Products?

Can you tell us more about 7-OH?

Kratom’s main psychoactive constituent is called mitragynine. This is what gives kratom its opioid-like, pain-relieving and euphoric effects. 7-OH is a more water-soluble version of that main active ingredient, but it is about five- to 50-fold more potent on the brain than mitragynine as an opioid receptor agonist or stimulator.

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. 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.

When you compare mitragynine to 7-OH, 7-OH is always more potent. Which is why it's more problematic: more potent and more concentrated in today’s products. It's the version of kratom substances that people can get addicted to.

How does that concentration change how it interacts with the body? Is it different between 7-OH and powdered kratom capsules?

Well, I would say there's not a different impact per se. It's that the powder kind of limits how much mitragynine and 7-OH you can get into your body.

The powdered leaf is about 1% mitragynine and maybe, at most, 0.1% 7-OH. If you’re making kratom tea, you have to put around 3 grams of powder into water to make tea and get a dose people are using it for, including legitimate medical purposes, such as to stop drinking alcohol or to wean themselves off of prescription opioids. 

Now, no one is going to ever ingest 3 grams of leaf powder – the leaves are very bitter, like most alkaloids are. Even if it’s in capsules, that’s like taking six extra-strength Tylenol capsules at a time.  It’s not a lot of fun to consume and acts as a limiting factor.

But when you take several times that amount of powder, isolate the mitragynine, concentrate it, and then put it into a little shot-sized beverage container like these 7-OH products have been seen in, you're getting multiples of doses that you would otherwise get in the powdered leaf. That's why the general feeling in the kratom consumer community is that the powder is kind of self-limiting, whereas these concentrated products can get you into trouble. 

So it’s similar to caffeine drinks at the highest levels of caffeine vs. coffee, or flower cannabis vs. shatter?

Exactly. It’s how we see caffeine energy drinks that are in these tiny containers with extremely high levels of caffeine. People can end up with heart attacks if they drink several of those, whereas you would have to drink a significantly higher amount of coffee to get into health problems. But caffeine, like most drugs, has varying impacts on different people’s systems. 

Same goes for shatter versus flower in cannabis. Even the most potent cannabis flower is 20-25% THC, but shatter and waxes have 70-95% THC. 

Are these 7-OH products dangerous for those who might be expecting something else given the insufficient labeling? Along the lines of “I’m expecting a diet soda and instead I’m getting a vodka-spiked energy drink?”

Exactly. That's a great analogy. 

Here in Colorado, think of the case of Daniel Bregger. He passed in 2021 because of poor labeling, and he didn’t know how much of these chemicals he was getting. His family said he was looking for an aid to help with his anxiety and accidentally consumed both one of these high-strength kratom products alongside the antihistamine diphenhydramine and died the next day. 

We should be concerned because there’s probably more people out there like him who unknowingly took more concentrated products without understanding how risky they can be, especially when taken with other drugs that cause sedation. 

Diving deeper on a dangerous combination:

Kroll also adds that a new paper just published looking at 551 deaths in Florida where mitragynine was detected post-mortem. In 93.5% of these cases, at least one other chemical was found in the system – most commonly fentanyl. “Kratom is rarely fatal on its own, owing in part to mitragynine and 7-OH-mitragynine being partial agonists at mu opioid receptors and being biased away from what’s called the beta-arrestin pathway, which causes a greater degree of respiratory depression in the brain’s control center,” said Kroll. 

What are some of the challenges on labeling as it relates to the supplemental industry?

That's a really great question. Because it's not a kratom problem; it's a supplement industry problem. We regulate herbal supplements and dietary supplements, like kratom, very differently than we regulate pharmaceuticals. 

The content, the purity, the dosing, the reproducibility are much stricter for prescription or over-the-counter medicines and almost non-existent for herbal medicines. There are increasing requirements for herbal medicines to list the actual amount of active chemicals, like echinacea for cold and flu, but kratom falls into this weird category now, because it's neither a drug nor a dietary supplement. 

Companies have tried to get it as an herbal supplement, but the FDA won't allow that. There's not a lot of financial incentive for a company to spend several hundred million or a billion dollars to try and get this approved as a drug, so that's not going to happen. That's a common problem with any herbal medicine. 

So, it's in this middle ground, where it doesn't fall under labeling requirements for dietary supplements. It doesn't fall under the purity requirements for either herbal supplements or drugs. It's in this weird, limbo area, and so drug regulators have tried to deal with it here and in other countries. That’s why you’re starting to see laws like Colorado’s and the FDA recommendation to place 7-OH on the Schedule I drug list. 

But does there remain some nuance to have in the conversation around regular powdered kratom in your view?

Yeah. I think, overall, people look at me and they say, "Dave, you're a pharmacologist who is with a major academic medical center. Why are you even giving voice to consumers who want to use kratom powder?" 

In an ideal world, kratom powder would be a well-regulated drug. But we have a very complicated healthcare system now, and people are hurting, and there are gaps in access to care. For good reason, the pendulum has swung on opioids the other way toward more of a controlled system.

At the same time, we have so many people who became opioid dependent and are cycling off the drugs and can’t access buprenorphine (an approved drug used to reduce withdrawal symptoms from opioid addiction), are suffering from chronic pain and depression, or don’t have health insurance. We should still have some compassion and empathy for our patients, friends and neighbors in these positions. 

So much of what we do, even in basic science, is we meet people who are suffering. It gives you a whole different view about the meaning of your work and makes you question some of the sort of absolutism that's in our drug regulatory structure, versus what the state of our health system is in reality.