Compounds from the Southeast Asian tree offer hope for a safer opioid alternative, but research could slow to a crawl as the DEA steps in

When Majumdar and his team started studying the compounds in the laboratory, they realized all three molecules were binding to the mu-opioid receptor—one of three known kinds of opioid receptors in the brain—in an unconventional way. Think of this receptor as the ignition to a “hybrid car,” Varadi explains, and the opioids that bind to it as keys. A typical opioid such as morphine turns on the “electric engine,” and that leads to a desired effect like pain relief. But it also starts up the “gas engine,” causing negative side effects. The mitragynine molecules from kratom seem to activate mostly the “good” systems, leaving behind the unwanted effects yet keeping pain relief.


Although the kratom compounds have yet to be clinically studied in humans, Andrew Kruegel, a pharmacologist at Columbia who was not involved in Varadi’s study, says the results hold promise for better designer painkillers. “Those compounds alone may already be superior to codeine and oxycodone. At a minimum, if you can get rid of respiratory [problems] then you can save thousands of lives,” Kruegel says. “But we can tweak their properties to make them even better than the natural starting point.” Or they would do so if the research were able to legally continue, he adds.


Scientists can obtain a license to study Schedule I drugs but they are hard to acquire and significantly slow down research, says Chris McCurdy, a kratom researcher at the University of Mississippi. “I don’t oppose it being regulated, I just oppose Schedule I,” he says. “That’s where the frustration comes in, realizing you have to shut everything down because we don’t have a Schedule I license.”
At the moment, neither do several other kratom researchers, including Majumdar. “We’ll have to destroy all our samples in the lab,” Kruegel says. The DEA’s emergency scheduling of kratom will expire after two years if the agency does not move to make the scheduling permanent. But for that to happen, Kruegel thinks scientists will likely need to show further proof that kratom is medically useful. “That we’ll have any progress in the next two years is very unlikely,” he says.