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n that day in 2005, the drug intelligence agent appeared unexpectedly at the poison control center in Boston. An unusual drug had been seized during a bust in New Hampshire, and he wondered if the toxicologists knew anything about it.

They didn’t. But before leaving, almost as an afterthought, he asked: Were there any other new and interesting drugs he should know about?

“I said, ‘Yeah, I’ve heard of this thing called kratom. It’s from Southeast Asia, and some use it to self-treat opioid addiction,’” recalled Dr. Edward Boyer, who was then a toxicologist at the center, but who now works at UMass Memorial Medical Center and Boston Children’s Hospital.

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Boyer didn’t think much of it. He’d heard it mentioned only briefly, from another drug researcher in Boyer’s hometown, Oxford, Miss.

“The next thing I know — the next week — there is this newsletter saying kratom is this drug of abuse,” Boyer said. The newsletter was from the Drug Enforcement Administration’s National Center for Drug Intelligence.

The more he learned about kratom, the more Boyer’s curiosity was piqued. And he wasn’t the only one. Other researchers began to tinker with it in the lab, breaking down the plant’s active chemicals, trying to understand how these compounds work on the brain, and whether it might have useful medicinal properties. They now know that the plant poses some risks — of causing seizures and addiction, and possibly even death — but it is what scientists still don’t know that interests them most.

“Is it an effective treatment for opioid withdrawal, or is it another pathway to addiction? I don’t think anybody has a defined concept of where it actually lies on that continuum,” Boyer said.

The DEA’s decision last month to outlaw kratom soon after Sept. 30 makes it much harder for researchers to figure that out — even as the nation confronts an epidemic of opioid abuse — they said in interviews with STAT. Labs will find it tougher to get kratom for their research, and studies will be vetted according to stricter government standards.

These researchers haven’t just been looking into whether kratom is a potential alternative to drugs like Suboxone, used to wean patients off opioids. They’re also trying to determine whether kratom might work as a less dangerous painkiller than drugs like OxyContin and morphine, so that patients could avoid opioids altogether. And they worry that this work will be sharply curtailed.

The DEA says that the ban will allow for some research to continue, but that it had to act to protect the public from a substance that, as of yet, has no medical uses and that has been blamed for more than a dozen deaths.

Kratom
Kratom leaves that Boyer hoped to use in a clinical trial, in the toxicology office at UMass Memorial Medical Center. Josh Reynolds for STAT

A new ‘drug of abuse’

Even back in 2006, researching kratom wasn’t exactly easy, Boyer said.

Not long after his conversation with the DEA special agent, Boyer decided to look more closely at kratom, which seemed to be growing in popularity. Getting government funding proved to be a quagmire: the National Institute on Drug Abuse didn’t want to fund kratom projects, saying it was a complementary and alternative medicine, while the National Center for Complementary and Integrative Medicine didn’t want to fund them because it was a drug of abuse.

Boyer had managed to get money to study how people addicted to opioids were reacting to a DEA crackdown on online pharmacies, which had sold painkillers without a prescription. “If you had a credit card, you could get OxyContin,” he said.

After weeks trolling through internet discussion forums, Boyer reported that a disproportionate number of people seemed to be turning to kratom.

Where the DEA saw a new drug of abuse, Boyer saw opportunity. In 2008, he and two colleagues filed a patent to use kratom or its chemical compounds as a new method for medically treating opioid withdrawal.

They were ready to start a clinical trial. Boyer, now a University of Massachusetts Medical School professor, received two large freezer bags stuffed with dried kratom leaves from his colleague in Mississippi. But instead of being used in a human experiment, the olive green leaves now sit in a cabinet of UMass Memorial Medical Center’s toxicology office. Boyer said it would have been “a bureaucratic nightmare” to go through the Food and Drug Administration approval process for the trial, so his team never submitted an application.

But in New York City, researchers would soon find that kratom had some promising medicinal properties.

Science, interrupted

To study how kratom works in the brain, Andrew Kruegel simply ordered the plant online. In the chemistry lab where he works at Columbia University, he boiled it in methanol, concentrating it down to something unrecognizable.

“You get this black, wax-like substance, it’s like a tar,” he explained. “You take that and you grind it up with acetic acid. The acid extracts the basic elements of the plant, the alkaloids.”

Those alkaloids are what create a drug-like effect.

Because brain cells are hard to grow in the lab, Kruegel used kidney cells instead, genetically modifying them so that their surface was adorned with opioid receptors.

These receptors are bit like the USB port on your computer: plugging in a mouse will have a different effect than plugging in a smartphone. And because kratom’s chemicals look different from opioids like morphine, Kruegel’s team figured that it probably had a slightly different effect.

They were right.

When an opioid binds to a receptor, it can trigger a few different responses in a cell. One is thought to be responsible for causing pain relief. Another is thought to be responsible for the negative side effects, such as respiratory depression, which is responsible for many opioid deaths.

Standard opioids, such as morphine, oxycodone, and fentanyl, set both of these protein cascades into motion.

By using fluorescent molecules to watch the proteins in action, Kruegel’s team could see that the main components of kratom mostly stimulated the painkilling response, but didn’t have as much of an effect on the proteins that caused the side effects. They published their results this past March.

The researchers still need to repeat these experiments in mice, and then in humans, before they could claim that they have used kratom to create an opioid-like painkiller without as many risky side effects.

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They may have reason to be cautiously optimistic — but the DEA’s announcement to make kratom as illegal as heroin and LSD has dampened their enthusiasm.

“I think it’s shortsighted, and I’m not pleased with it, because it’s certainly going to hinder our research to a dramatic degree,” said Kruegel.

He hopes to get permission from the DEA to keep working with kratom — but even if he does, he said, getting the plant is going to be a hassle.

“There is nowhere to buy the plant unless I am going to go to Indonesia and contact plantation owners,” he said. But that is hard to imagine without enormous tangles of red tape.

Susruta Majumdar, a researcher at Memorial Sloan Kettering Cancer Center who has been working on kratom-based chemicals, is also worried about getting the building blocks he needs to continue his research.

“What we are going after is a non-morphine-like opioid, which would still exhibit morphine-like analgesia, but would not be addictive,” he said.

Just days after the DEA announced that it would ban kratom, Majumdar published a study in mice, showing that chemicals isolated from the plant and then modified in the lab could not only weaken pain without causing severe side effects, but also seemed to be less addictive than many opioids currently being prescribed.

He is not a kratom advocate, he told STAT, but the ban will slow his work. “It does hurt me, there is no question,” he said.

DEA spokesperson Russ Baer, however, said that his agency supports research. “As is the case with any controlled substance, DEA will implement aggregate production quotas for Kratom and make available an adequate and uninterrupted supply of research grade material to accommodate valid scientists and researchers,” he wrote in an email to STAT.

A death blamed on kratom

Researchers know that kratom is not a harmless substance. They know that, until now, it has been completely unregulated, and has often been adulterated with opioids. They know that it may itself be addictive, and may prevent those with opioid addiction from seeking medical treatment. They know that it has been linked to seizures (usually in conjunction with other drugs) and other side effects. They know that the DEA has attributed 15 deaths to kratom between 2014 and 2016.

Yet they still feel that that litany of facts is outweighed by all that isn’t known.

“We do not know what the actual health impact is of kratom in the United States,” said Oliver Grundmann, a toxicologist at the University of Florida. He added, “the profile of those who are using kratom is not the usual profile of illicit drug users or those who seek the high … of a drug.”

Grundmann had planned to conduct a survey that would assess just how widespread kratom use is in the United States, but the DEA’s announcement has made him rethink the project.

He understands the agency’s concern, but also wonders about some of the facts they use to justify their decision. For example, the agency cited a report published in July, showing a tenfold increase in the number of calls to poison centers from 2010 to 2015.

Grundmann points out that the total number of calls — 660 — is tiny when compared with those that come in about something as easy to buy as Tylenol.

But there is at least one researcher who adamantly supports the ban.

He isn’t a toxicologist. Instead, he’s an infectious disease researcher at the National Institutes of Health named Dr. Lawrence Fox. His support for the ban is deeply personal: In 2013, his son Alex, who was 20, died after ingesting kratom.

Alex had struggled with opioid addiction in the year before his death, but he had been off the drugs for a while. He had broken off his relationship with the friends who had introduced him to prescription pain pills, and had worked on his addiction with his psychiatrist and therapist.

But there was one Friday night when he was too drowsy to join his family for dinner. The next day, his father found the house eerily quiet. “It was just too quiet from his bedroom,” he said. “I went to see how he was doing. I touched him and he was cold.”

Fox found packages of kratom in his son’s desk, and asked the medical examiner to do special tests to look for the plant’s chemicals in his son’s blood.

He remembered his son as someone who was equally at ease discussing HIV research as he was discussing symphonies. “He could write poetry with alternating verses of English and German, and the rhyme and meter flowed beautifully in both languages,” he said.

He’s glad that kratom won’t be as easily available as it was when Alex took it, and is glad that the ban will counteract internet ads, which made the substance sound harmless.

But Fox also thinks kratom is worth researching.

“I think it’s quite conceivable that there may be uses for the drug or the active ingredients in the drug in ways that are valuable and safe,” he said. “That would involve understanding the receptors that it binds, the various effects that it has, and in particular, providing a reliable dose of the drug itself, considering that it has the possibility of killing people.”

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  • “..had worked on his addiction with his psychiatrist and therapist.” Most likely Alex was prescribed psychotropic drugs with a high likelihood that at least one of them was a benzodiazepine. Benzos, of course, potentiate the action of some other drugs (as in the case of Prince who also had Fentanyl in his system). This article fails to mention what other drugs were present in Alex’s tox screen. Additionally, the FDA, like too many federal agencies, is captured by the entities it is meant to police. The pharmaceutical industry does not want a drug that will interfere with the obscene profits it derives from its toxic pain medications, so research on kratom and marijuana must be hobbled.

  • This is not only for Opiate addicts. I have never used opiates except twice for the dentist and once for a surgery. Never had an issue with them and in fact, I dislike them very much.
    However, Kratom has helped my treatment resistant anxiety and depression and has helped me to quit alcohol (which I abused for 20 years!!). I am an honor student in school studying computer science.
    I took kratom for 1 year and I have been alcohol free since that time. In that year, I took the same dose consistently. I never needed an increase and my dosage is very very low (pretty much right at “threshold”).
    When I quit, I did not get any symptoms other than a slightly runny nose and tiredness. I continued on with my normal life while I was withdrawing from this supposedly “dangerous” drug!

  • This plant saved my life as well, I was able to quit opiates, I was an opiate addict for years,even an iv user and wanted out desperately but nothing worked for me including na meetings suboxone, or methadone. Suboxone and methadone just get you high, so all they do is replace the drugs with a more accessible high that’s legal. Kratom however got my through the withdrawals, I was even able to continue working it has helped greatly with my depression and anxiety, which were to of the main reasons I used drugs in the first place. And at the same time I became myself again, because I was not high all the time anymore and not myself. This should not be banned, look at how bad the opiate addiction crisis is in america. This plant helps to free people from thier addiction, that should be enough to not ban it alone. It helps many people for several things, people that have never been addicts find releif with kratom, without all the bad side effects as prescription meds.

    They even stated in this article here, tylanol is more dangerous than kratom, TYLANOL is more dangerous than kratom, so why can they even begin to try and ban it?????

  • My ex used to get envelopes of this stuff from a “pharmacy” in Mexico, via the mail. The packages originated in India, and the English translated words on the labels were usually spelled wrong. She’d read it was used for “restless legs” treatment in an online forum. Trust me- when she’d use this mixed with lorazapam, clonazapam, tramadol, and ambien- it did more than treat “restless legs.” If you’re ordering stuff from India, shuffled through Mexico, are mixing with Rxs prescribed by 2-3 different doctors, and none of them know the truth of what you are taking- there’s a problem. I do remember her complaining of bad gastric-GI issues when taking… imagine that, from grass clippings with no FDA oversight you ingest to self-medicate.

    • Kratom has effectively replaced ALL of these type drug’s for me and I’ve never had to get anything through Mexico. You do have a good point about mixing and not telling your doctor (this is basic common sense) but the idea is to give those the right to choose a safe alternative to the drugs you listed that have killed countless and the side effects are absolutely ridiculous for most using these FDA approved drugs (I’ve taken all of those you listed and I’m sure your EX was like a walking zombie w/o the kratom involved). You may want to go here https://www.reddit.com/r/kratom/ and learn a little more about what you are talking about about in regards to these “grass clippings”. Gastric issues? Take some Magnesium Citrate. Constipation is a real side effect of both the Tramadol and the kratom.

  • “Fox found packages of kratom in his son’s desk, and asked the medical examiner to do special tests to look for the plant’s chemicals in his son’s blood.”

    And? What did they find in his blood? Did they also find rock ‘n roll music or marijuana in his room? How about the opioids he was already addicted to? This is a poorly sourced assertion and about on par with the flimsy evidence cited by the DEA. I would have expected better from STAT, but maybe I shouldn’t have.

    • Seriously – What were the results of the toxicology report? What else was found in his blood?

      Sounds to me like his son died of an opioid overdose, which would make a lot more sense given the fact that he was actually addicted to them – or a complication from medications prescribed to him for withdrawal.

  • I like how you say “blamed for a dozen deaths” rather than cause a dozen deaths in this article because in all the reports I’ve read were mitrgynine speciosa was blamed for the death there were lots and lots of other drugs in the mix that are historically known to be toxic and some that have even killed on there own.

    • This article is proof that even medical professionals or those who chronicle/journal about them are susceptible to sensationalism and prone to deference to authority, such as continually regurgitating the DEA’s description of kratom as “a drug of abuse” without any evidence presented to back it up, and despite the preponderance of evidence to the contrary.

      They go further by saying that healthcare professionals “know” that kratom can cause seizures (really? where’s the evidence?) and death (to your point, they only cite deaths where numerous other drugs – some very dangerous – were present).

      All in all this is a very biased article that still manages to refute the DEA’s ridiculous claims that there are no medical benefits derivable from kratom. There are over 8 studies on the effects of kratom’s chemical components that I can think of and provide links to off the top of my head.

  • Kratom saved my life. I was diagnosed with bipolar at age 16 and years of prescription drugs left me no better off. I gave up and spiraled into a deep depression, until I found this plant. Now I am a hardworking, tax-paying member of society and I live a life I never could have dreamed just a few short years ago.

    Please do not make me a criminal for wanting relief from my bi-polar

    Current peer reviewed studies on Kratom and its constituents have shown that Kratom has no acute toxicity, displays powerful antioxidant and antibacterial properties, assists with drug and alcohol withdrawal symptoms, contains several oxindole alkaloids which have exhibited potent immunomodulation properties, and even contains constituents that have exhibited anti-cancer properties! A brief search in any scholarly database will present many peer reviewed studies and clinical trials that can attest to the medical potential of this plant. In short, Kratom does not present a significant threat to human health or safety on any level and does not belong in Schedule 1, period.

    https://www.youtube.com/watch?v=kzRlc08sNV4

    • Wikipedia isn’t an academic or scholarly resource. Anyone can edit Wikipedia. That ought to tell you all you need to know!

    • I han 69 years old and have been taking kratom for over 3 years and have never had any problem with it. I have fibromyalgia,3 back surgeries, thyroid issues, allergies , anxiety and depression and have no problem taking kratom. Never even felt a high on it. It is so wrong to ban it when I have seen so many people(including myself) feel so much better with their health problems.

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