FDA Declares Kratom an Opioid. We’re Here to Explain What It Does.

The Scientist speaks with a clinical toxicologist to discuss how the supplement acts in the brain and what the agency's declaration means for research.

By Jim Daley | February 7, 2018

ISTOCK, AR30MM

The Food and Drug Administration (FDA) announced on Tuesday (February 6) that kratom, a popular herbal supplement, is a dangerous drug with “opioid properties.” The announcement came after the FDA evaluated the potential for kratom abuse using the Public Health Assessment via Structural Evaluation (PHASE) methodology, which simulates the molecular structures of a substance using 3-D computer modeling.

“[W]e feel confident in calling compounds found in kratom, opioids,” FDA Commissioner Scott Gottlieb declared in the statement. “And it’s an opioid that’s associated with novel risks because of the variability in how it’s being formulated, sold and used recreationally and by those who are seeking to self-medicate for pain or who use kratom to treat opioid withdrawal symptoms.”

Clinical toxicologist Oliver Grundmann of the University of Florida coauthored a study in 2017 on the neuropharmacology of kratom and its potential for abuse. He spoke with The Scientist about the plant and the FDA’s announcement.

Oliver Grundmann

The Scientist:  Commissioner Gottlieb declared kratom was an opioid that is not safe for medical use. Can you tell me how kratom works pharmacologically?

Grundmann: At low concentrations, if you take it you get more of a stimulant effect; in higher concentrations you get more of an analgesic, opioid-like effect. So, there’s a dose-dependent distinction in its effects.

The likely opioid-like compounds, or the compounds that act on the opioid receptors, are mitragynine and 7-hydroxy mitragynine. These are the two that have been currently identified and where extensive research is available. . . .

On the molecular level, what we know in terms of interaction with the different opioid receptors is that yes, they bind to the opioid receptor. . . . But how they interact with the opioid receptor is distinctly different from classical opioids. If you look at morphine or at something like fentanyl . . .  what we usually look at when we classically look at opioid receptors, these are G-protein-coupled receptors, where basically the morphine or another binding agent binds from the outside to the receptor and then you have a kind of second-messenger cascade that happens inside the cell.

How they interact with the opioid receptor is distinctly different from classical opioids.

Now, what we know about the opioid receptors . . . is that opioid receptors also recruit beta-arrestin. [It] has been shown to be responsible for a lot of the negative effects, especially in regards to respiratory depression and potentially even in regards to the addictive symptoms . . . that are associated with opioid use, misuse, leading to abuse. That is something that mitragynine is not doing. Mitragynine does not recruit beta-arrestin.

TS: Would you say that you agree with the FDA’s classification of [kratom] as affecting the body just like opioids, or no?

Grundmann: The science is on the same page in regards to mitragynine and 7-hydroxy mitragynine and thereby certain compounds in kratom acting on opioid receptors. My concern is . . . we’ve got roughly 5 million kratom users—roughly, it’s a very rough estimate. In my survey that was published in 2017 [I] showed that this is a distinctly different user population from what you would expect to find in opioid users.

I fear that by banning kratom, we are creating a significant issue by hindering research. I am a proponent of regulating kratom as limiting the excess, as controlling products that are entering the United States [to ensure] they show quality, that there is actually kratom inside when kratom is mentioned on the label. I support that health care providers should be serving as intermediaries to provide patients and consumers with advice on what they actually take.

But phasing it into Schedule 1 makes it very hard to further conduct research. And this is a new class of endo-alkaloids that act very distinctly different on opioid receptors. And just because the FDA hasn’t received an NDA [New Drug Application] or IND [Investigational New Drug application] to actually conduct a study with mitragynine to move it into a clinical trial, which we know costs . . . millions of dollars, doesn’t mean that it doesn’t have value for these 4 or 5 million kratom users, who I feel would have to go back to using prescription opioids or potentially going to street drugs.    

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Avatar of: Already

Already

Posts: 9

February 8, 2018

Mityrigynine, a substance in Kratom, sounds like the key to overcoming the deaths associated with opioid abuse.  It apparently doesn't recrutis beta-arrestin, which is the killer pathway of opioids, shutting down respiration.   It could be a key to developing drugs for pain relief which apparently don't kill and maybe "potentially even in regards to the addictive symptoms", won't even cause addication, and might even eliminate addictive craving.

Kratom is an evergreen tree in the coffee family, but it doesn't appear coffee beans share any of its effects.

I hope there is a common sense approach to investigating Kratom, actually substances such as mityrigynine, since it might be a potential relieving substance for opioid abuse.

Avatar of: abau

abau

Posts: 1

February 8, 2018

US is obsessed with the criminality of narcotics. Politicians, especially Republicans, have a strong, prejudiced bias in favor of policing and restriction. None of this has made any difference in dealing with the problem. In fact, all it has done is to keep up the price of illegal narcotics thereby ensuring the continuation of supply. Decriminalization and provision of narcotics to addicts through a registered, overseen medical pathway would eliminate illegal supply owing to a massive reduction of prices. Enormous savings through elimination of the various federal and state drug enforcement agencies, reduction of prisons and court costs would provide tthe resources for improved care not only of addicts, but of other psycholgically impaired, often homeless people. Further, but very importantly, placement of narcotic delivery within a medical care system would remove the attraction of illegality for the young. The system needs to change; the current provisions are not only ineffective, but are responsible for driving addiction and the associated damage to society, let alone driving the economy of drug trafficking and the attendant criminal cartels, and criminal intervention agencies.

Avatar of: MagmaHombre

MagmaHombre

Posts: 1

February 12, 2018

Continuation of the opioid addition crisis is guaranteed by the FDA's action which is motivated more by the desire to protect the pharmacuetical industry's profits, the future income stream to the FDA from the review fees for patentable Kratom derivatives, and the FDA-Pharm industry control of health care than by any desire to protect the public or improve public health.  Another example of FDA corruption.   Its time to abolish the FDA.

Avatar of: concerned-native

concerned-native

Posts: 2

February 13, 2018

I saw a report on PBS that Japan is studying this PLANT (not drug) for their treatments.  FDA is ultimately doing this to protect big-pharma greed and control.  Recall what FDA did about the ancient herb ma-huang...

Avatar of: wolfie

wolfie

Posts: 2

February 15, 2018

I believe kratom should be used the way it has been used for thousands of years in South East Asia, which is by plucking the leaves from the actual tree, removing the central vein and chewing it with a potentiater such as lime. It provides an excellent anti-depressant effect in such a dosage and as such is benevolent for use.

Powdering it up and taking 3,4,5 grams at a time as I have seen recommended on various websites is just asking for trouble.

Allowing Big Pharma to take it and start extracting various components would be dangerous. Look at cocaine, once a helpful herb when chewed in the living leaf stage helpful for preventing hypoxia at great elevations but now a scourge of humanity as an extractd powder.

Putting it into the same category as other supposedly dangerous drugs only makes it's abuse certain.

Avatar of: wolfie

wolfie

Posts: 2

Replied to a comment from MagmaHombre made on February 12, 2018

February 15, 2018

Yes, ABOLISH the FDA!!! I am with ya for sure!

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