The green powder from Southeast Asia could help fight addiction—but is that the whole story?
Last night's episode of Hamilton’s Pharmacopeia looked at kratom, a drug known in the US mostly as a green powder you can find in gas stations or head shops. It has a variety of uses, but according to toxicology and emergency medicine doctor Kavita Babu—who’s studied kratom for 12 years—the drug developed a higher profile in the mid 2000s as a DIY method for weaning people off opioids. You still need willpower, users say, but kratom can cut down on opioid cravings and withdrawal symptoms, allowing them to get back to their lives with few, if any, side effects. But as kratom’s usage and visibility have expanded in recent years—to the point that a sub shop in Arizona installed a kratom vending machine last year—the government has taken notice. On November 14, the FDA issued a public health advisory warning that kratom acts like opioids, carrying similar risks of abuse and even death. The agency stated that it would be working to block imports of the substance to head off a possible escalation of America's opioid epidemic, or the development of a parallel health crisis. So who’s right about kratom? Could it actually have a place in opioid addiction treatments? Kratom is a plant from the same family as the coffee shrub that grows in Southeast Asia, where locals have eaten it raw, brewed it as tea, or turned it into liquids or powders for centuries. The drug's effects set in quickly and last for several hours, depending on the dose taken. In low doses, say two to three grams of powder in water, it acts like a stimulant, providing a mild buzz users liken to caffeine; in higher doses, it can relieve pain, relax muscles, reduce inflammation, and lead to mood improvements. It can be used for anything from a mild pick-me-up to serious self-administered chronic pain, depression, anxiety, or addiction management. Experts estimate that 4 to 5 million Americans used kratom as of 2016; a survey of thousands of users conducted last fall by pharmacologist and kratom researcher Oliver Grundmann suggests two-thirds of respondents used it to treat chronic pain or emotional or mental stress. Only a little more than a third—mostly younger people with self-insurance, Medicare, or no insurance—said they used it for opioid addiction issues. Many respondents also told Grundmann that they used kratom for pain management to avoid opioids, using just three to five grams at a time— far below the 10 to 15 grams suggested to really get high. But the Botanical Education Alliance (BEA), which works to protect herbal substances from over-regulation, thinks people using kratom to treat addiction are actually overrepresented in the media. The BEA argues that most users use it “similar to St. John’s wart for a patient with depression, or valerian root for a patient with anxiety.” Furthermore, scientists have identified two key ingredients in kratom—mitragynine and 7-hydroxymitragynine—that interact with opioid receptors in cell and animal studies. So you can consider them opioids, but they seem to trigger the positive effects of opioids in the brain, triggering less negative side effects than other opioids as well. It takes longer to build up a tolerance to kratom than to traditional opioids, and when one does develop a dependency, the withdrawal symptoms are reportedly far milder than those associated with mainstream opioids. These facts certainly suggest kratom could be an innovative, if not ideal, pain killer; some researchers also claim it would be a good replacement for methadone or buprenorphine, opioids that stay in the body longer than heroin or most prescription drugs and don’t lead to as strong of a high. Despite being used to blunt cravings and control withdrawal, those substances still have side effects, and can be abused; kratom might be kinder and safer. But there’s still a lot we don’t know about kratom, and how it might affect humans. “At some point,” Grundmann states, “we need to conduct studies that are done on standardized extracts containing standardized amounts of mitragynine so we can compare the effect of doses and how patients react over time.” “I'm very concerned with the increased use of opioids resulting in overdose and death,” said emergency medicine clinician Megan Rech, who's also studied kratom. “I think kratom offers an exciting alternative to opioids,” she continues, before qualifying that she “wouldn't recommend routine use until further studies evaluate safety and efficiency.” And the DEA and FDA have been eyeing kratom cautiously over the past five years, too. In 2012 and 2014, the latter organization allowed customs agents to seize packages of kratom coming in to the country; late last year, the DEA moved to make mitragynine and 7-hydroxymitragynine Schedule I drugs, placing them under the same criminal restrictions as heroin, LSD, or weed. But these efforts weren’t very effective: The American Kratom Association claims that hundreds of millions of doses still make it into the country every year, and a massive public backlash led the DEA to temporarily abandon its push to schedule kratom. So kratom users and activists aren't very worried about the recent FDA advisory, but the government still thinks kratom is dangerous and may make more pushes to ban it. The drug's already illegal in Illinois and Louisiana, and its active ingredients are illegal in Alabama, Arkansas, Tennessee, Vermont, and Wisconsin, as well as other localities. Other states have considered similar bans, and some laws have come based on the DEA and FDA’s anti-kratom actions. The agencies also claim there was a tenfold increase in poison control center calls related to kratom between 2010 and 2015, with records of 36 worldwide deaths associated with the substance. They note that it's banned in 16 other nations, further claiming it's been linked to opioid-like symptoms as well as seizures and psychotic episodes. But activists and neutral scientists have ripped these claims to shreds: For one, the tenfold increase shrinks in comparison to the number of kratom users in America, and in all but one of the reported deaths, other substances may have been at play, including opioids. “After more than a decade of increasing kratom use in the US, the FDA is pointing to fewer than 40 deaths coincident with kratom use—none of which were definitively caused by kratom—and calling the plant ‘deadly,’” said psychologist and kratom researcher Marc Swogger. “This is hyperbole, and it's confusing and irresponsible.” Some have speculated the agencies’ rush to ban kratom means they're interested in protecting opioid revenues, but it’s more likely they’re spooked by any risk that kratom use could go in the same direction as prescription opioids. “I can understand, from a regulatory and public health standpoint,” said Grundmann, “that they don’t want another drug out there that acts on opioid receptors… especially one in which we simply don’t know enough to make a less qualified statement about its potential for adverse effects." And that fear’s pretty evident in the recent FDA advisory. “We’ve learned a tragic lesson from the opioid crisis,” wrote Commissioner Scott Gottlieb. “We must pay early attention to the potential for new products to cause addiction, and we must take strong, decisive measures to intervene.” There is one big reason, however, to worry about kratom as a health risk: adulteration. Pro-herbal groups like the BEA argue that measures are in place to prevent the sale of contaminated product, but, Babu argues that as the kratom market has exploded, it's also created competition to offer stronger doses. “We’re seeing that kratom can be adulterated with its own active ingredients,” she said. “It looks like you’re getting something natural, but really it’s been adulterated.” At least one study has found higher-than-natural concentrations of kratom's opioid-like ingredients in samples of US vendors’ products; the FDA also claims hat some end sellers have laced their kratom with opioids. “What we knew about kratom over the past ten years—that it was relatively safe,” Babu continued, “has changed because of adulteration… Our experience with this plant is no longer our experience with the plant as we knew it.” She also worries that we may see more cases of overdose, like the death of New York State sergeant Matthew Dana this year, that may have actually been caused by kratom—or more cases of serious addiction of because of adulteration. If the occurrence grows more common or extreme, kratom could lose its utility to opioid addicts, becoming the threat the agencies say it is. But kratom researchers and advocates agree that banning the substance is no good. For one, where will current kratom users—especially those who do rely on it to manage their addictions or as a replacement for traditional opioids—turn if it’s scheduled? Grundmann ponders the effects of such actions: “Are they talking to their physicians about going back to opioids?… Are they going back to heroin, then? “It is likely that reducing access to kratom now will worsen the opioid crisis,” said Swogger, “especially for people who are unable to access other treatments” for pain or addiction. And experts argue that, instead of banning the substance, we should be studying kratom to develop affordable drugs we actually can regulate. Studies of synthetics akin to kratom's main ingredients are underway, and there could be more studies of the plant itself—which researchers are eager to undertake while lacking the resources to pursue. In the meantime, there could be new regulatory protocols to better monitor kratom’s purity in the US, as well as education on how to most safely source and consume kratom. One thing's for sure: Scheduling kratom would make those measures more difficult to pursue, possibly endangering lives in the process. The question isn’t whether kratom has value in the opioid crisis: It's whether we'll allow the substance to become something illicit and, by extension, more dangerous and less helpful. By Mark Hay