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.