The leaves of the herb kratom (Mitragyna speciosa), a native of Southeast Asia in the coffee family, are used to relieve pain and improve mood as an opiate substitute and stimulant. The herb is also combined with cough syrup to make a popular beverage in Thailand called “4x100.” Because of its psychoactive properties, however, kratom is illegal in Thailand, Australia, Myanmar (Burma) and Malaysia. The U.S. Drug Enforcement Administration lists kratom as a “drug of concern” because of its abuse potential, stating it has no legitimate medical use. The state of Indiana has banned kratom consumption outright.



Now, looking to control its population’s growing dependence on methamphetamines, Thailand is attempting to legalize kratom, which it had originally banned 70 years ago.



At the same time, researchers are studying kratom’s ability to help wean addicts from much stronger drugs, such as heroin and cocaine. Studies show that a compound found in the plant could even serve as the basis for an alternative to methadone in treating addictions to opioids. The moves are just the latest step in kratom’s strange journey from home-brewed stimulant to illegal painkiller to, possibly, a withdrawal-free treatment for opioid abuse.



With kratom’s legal status under review in Thailand and U.S. researchers delving into the substance’s potential to help drug addicts, Scientific American spoke with Edward Boyer, a professor of emergency medicine and director of medical toxicology at the University of Massachusetts Medical School. Boyer has worked with Chris McCurdy, a University of Mississippi professor of medicinal chemistry and pharmacology, and others for the past several years to better understand whether kratom use should be stigmatized or celebrated.



[An edited transcript of the interview follows.]



How did you become interested in studying kratom?

A few years ago [the National Institutes of Health] wanted me to do a bit of consulting on emerging drugs that people might abuse. I came across kratom while searching online, but didn’t think much of it at first. When I mentioned it to the NIH, they suggested I speak with a researcher at the University of Mississippi who was doing work on kratom. [The researcher, McCurdy,] assured me that kratom was fascinating, and he started to go through the science behind it. I decided I needed to look into it further. Talk about chance favoring the prepared mind. I no sooner hung up the phone when a case of kratom abuse popped up at Massachusetts General Hospital.



How did this Mass General patient come to abuse kratom?

He was a [43-year-old] successful software engineer who had been self-medicating for chronic pain [as a result of thoracic outlet syndrome, a group of disorders that occurs when the blood vessels or nerves in the space between the collarbone and the first rib—the thoracic outlet—become compressed, causing pain in the shoulders and neck as well as numbness in the fingers]. He had started with pain pills, then switched to OxyContin, and then moved to Dilaudid, which is a high-potency opioid analgesic. He had gotten to the point where he was injecting himself with 10 milligrams of Dilaudid per day, which is a large dose. His wife found out and demanded that he quit.



He read about kratom online and started making a tea out of it. For the most part, this helped him avoid the opioid withdrawal he had been experiencing. After he started drinking the kratom tea, he also began to notice that he could work longer hours and that he was more attentive to his wife when they would speak. He began experimenting with ways to boost his alertness by adding modafinil [a U.S. Food and Drug Administration–approved stimulant] with his kratom tea. That’s when he started to seize and had to be brought to the hospital. I have no idea how that combination of drugs caused a seizure, but that’s how he ended up at Mass General Hospital. Nobody there had heard of kratom abuse at the time. [Boyer and several colleagues, including McCurdy, published a case study about this incident in the June 2008 issue of the journal Addiction.]



The patient was spending $15,000 annually on kratom, according to your study, which is quite a lot for tea. What happened when he left the hospital and stopped using it?

After his stay at Mass General, he went off kratom cold turkey. The fascinating thing is that his only withdrawal symptom was a runny noise. As for his opioid withdrawal, we learned that kratom blunts that process awfully, awfully well.



Where did your kratom research go from there?

I had a small grant from the NIH’s National Institute on Drug Abuse to look at individuals who self-treated chronic pain with opioid analgesics they purchased without prescription on the Internet. This was an extremely restricted population, but it nonetheless measures in the hundreds of thousands of people. About the time I started the study, the DEA and the state boards of pharmacy began shutting down online pharmacies, so sources of pain pills for these hundreds of thousands of people in the United States dried up instantaneously. A number of them switched to kratom.



How many people are using kratom in the U.S.?

I don’t know that there’s any epidemiology to inform that in an honest way. The typical drug abuse metrics don’t exist. But what I can tell you, based on my experience researching emerging drugs of abuse is that it is not difficult to get online.



How does kratom work?

Its pharmacology and toxicology aren’t well understood. Mitragynine—the isolated natural product in kratom leaves—binds to the same mu-opioid receptor as morphine, which explains why it treats pain. It’s got kappa-opioid receptor activity as well, and it’s also got adrenergic activity as well, so you stay alert throughout the day. This would explain why the guy who overdosed described himself as being more attentive. Some opioid medicinal chemists would suggest that kratom pharmacology might [reduce cravings for opioids] while at the same time providing pain relief. I don’t know how realistic that is in humans who take the drug, but that’s what some medicinal chemists would seem to suggest.



Kratom also has serotonergic activity, too—it binds with serotonin receptors. So if you want to treat depression, if you want to treat opioid pain, if you want to treat sleepiness, this [compound] really puts it all together.



Overdosing and drug mixing aside, is kratom dangerous?

People are afraid of opioid analgesics because they can lead to respiratory depression [difficulty breathing]. When you overdose on these drugs, your respiratory rate drops to zero. In animal studies where rats were given mitragynine, those rats had no respiratory depression. This opens the possibility of someday developing a pain medication as effective as morphine but without the risk of accidentally overdosing and dying.



What barriers have you run into when trying to study kratom?

I tried to get an NIH grant to study kratom specifically. When I went to the National Institute on Drug Abuse, they said they’d never heard of that drug. When I went to the National Center for Complementary and Alternative Medicine, they said this is a drug of abuse, and we don’t fund drug of abuse research. They want drugs that are used therapeutically. [A team led by McCurdy, who confirms that it is difficult to get funding to study kratom, did manage to secure a three-year grant from the NIH Centers of Biomedical Research Excellence to investigate the herb’s opioid-like effects.]



So the study of this type of substance falls to academics or pharma companies. Drug companies are the ones who can isolate a particular compound, do chemistry on it, study and modify the structure, figure out its activity relationships, and then create modified molecules for testing. Then you have eventually file for a new drug application with the FDA in order to conduct clinical trials. Based on my experiences, the likelihood of that happening is reasonably small.



Why wouldn’t large pharmaceutical companies try to make a blockbuster drug from kratom?

At least one pharma company [Smith, Kline & French, now part of GlaxoSmithKline] was looking at it in the 1960s, but something didn’t work for them. Either it wasn’t a strong enough analgesic or the solubility was bad or they didn’t have a drug delivery system for it. To the state of the art pharmaceutical business thinking in 1960s, this compound was not sufficient to be brought to market. Of course, now that we have a country with many addicted people dying of respiratory depression, having a drug that can effectively treat your pain with no respiratory depression, I think that’s pretty cool. It might be worth a second look for pharma companies.



There are reports that Thailand might legalize kratom to help that country control its meth problem. Could that work?

They can decriminalize kratom until they’re blue in the face but the reality is that kratom is indigenous to Thailand—it’s readily available and always has been. Yet drug users are still opting for methamphetamines, which are stronger than kratom, not to mention dirt cheap and widely available. I suspect that Thailand is just trying to say that they’re doing something about their meth problem, but that it might not be that effective.



Is kratom addictive?

I don’t know that there are studies showing animals will compulsively administer kratom, but I know that tolerance develops in animal models. I can tell you the guy in our Mass General case report went from injecting Dilaudid to using [$15,000] worth of kratom per year. That kind of sounds addictive to me. My gut is that, yeah, people can be addicted to it.



What are the dangers posed by kratom use or abuse?

It’s just like any other opioid that has abuse liability. Heroin was once marketed as a therapeutic product and later was criminalized. Yet OxyContin [a painkiller with a high risk for abuse] was marketed as a therapeutic but has remained legal. You put the proper safeguards in place and hope that people won’t abuse a substance. Speaking as a scientist, a physician and a practicing clinician, I think the fears of adverse events don’t mean you stop the scientific discovery process totally.