Uncovering the Pain-Relieving Effects of Kratom

Published on 28 June 2019

As research continues at the Center for Clinical Pharmacology to improve the treatment of pain, Susruta Majumdar, Ph.D., associate professor of medicinal chemistry and pharmacology at St. Louis College of Pharmacy, has been working collaboratively with scientists at the center and Columbia University to examine the biological effects of kratom and its potential to create safer alternatives to the use of opioid pain medications. In recent months, work conducted by Majumdar and his team has uncovered what may be the source of kratom’s pain-relieving effects.

Native to the tropical jungles of Southeast Asia, Kratom is a tree that has long been used as a traditional medicine by those in its native regions, with its leaves being consumed as a pain reliever and treatment for opioid abuse. Kratom’s increasing popularity in the United States has lead researchers to more closely study the pharmacological activity of the substance.

Initial findings have indicated that mitragynine, the major active alkaloid found in kratom, and its related compounds have the ability to bind to opioid receptors and provide therapeutic effects, such as pain relief, while inducing fewer negative side effects than typical opioids. However, new research conducted by Majumdar and his colleagues, Jonathan A. Javitch and Dailbor Sames from Columbia University, indicates that an alkaloid known as 7-hydroxymitragynine (7-OH), actually provides the pain-relieving effects of mitragynine. The team’s findings were recently published in in the multidisciplinary research journal ACS Central Science.

“What we found through our studies in mice was that the 7-OH metabolite was responsible for inducing most of the pain relief the mice experienced,” said Majumdar. “Through our research, we discovered that the opioid pharmacology of mitragynine is complicated by the role of 7-OH in mediating its activity. In mouse and human liver preparations, the analgesic effects of mitragynine are actually dependent on 7-OH as a metabolic mechanism.”

While mitragynine was found in high concentrations in the brains of mice, Majumdar and his team discovered that it was not responsible for the direct activation of opioid receptors. Instead, Majumdar’s research found that that the 7-OH metabolite is formed from mitragynine in mice, and brain concentrations of 7-OH are sufficient enough to explain all or most of the opioid-receptor-mediated pain reliving effects of mitragynine.

“We believe mitragynine and the related compounds present in kratom have great potential as future pain relief therapies, but as exploration of their potential continues, our research demonstrates the importance of carefully considering the role of metabolic processes and their effects on these compounds,” said Majumdar. “Our research also raises important questions about the interpretation of the existing data on mitragynine and highlights critical areas for further research in animals and humans.”

Amid ongoing conversations about the role of kratom in the larger opioid crisis, Majumdar’s work is providing new insights. By deepening our understanding of how kratom and other opioids affect the brain and provide relief for pain, Majumdar hopes to someday develop new medications that mimic opioids in terms of pain relief but do not carry the same risk for addiction.

“Given that kratom-derived templates are atypical opioids, they present fewer adverse effects, such as dependence and tolerance,” said Majumdar. “As a result, these templates may be used as starting points to develop new medications with the potential to aid in mitigating the opioid epidemic that continues to impact the U.S.”

View the full abstract of the study in ACS Central Science. For details about the wide range of research currently underway at the Center for Clinical Pharmacology, visit clinicalpharmstl.org.

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