Kratom's reputed pain-relief benefits could come from one of its metabolites

May 29, 2019

Kratom is a Southeast Asian tree with a long history of use in traditional medicine. In the region, the plant's leaves are widely consumed for pain relief, treatment of opioid addiction and other uses. Though its efficacy and safety are unproven, kratom use has spread to the U.S. and Europe. Now, researchers report in ACS Central Science that a metabolite of a kratom alkaloid could be responsible for the treatment's therapeutic effects.

Currently, kratom is legal and available in the U.S. as a gray-market product, but it has an uncertain regulatory future. In the meantime, scientists are investigating the substance's physiological effects. Some prior research attributed these effects to mitragynine, the major active alkaloid in kratom, and its binding to an opioid receptor. However, 7-hydroxymitragynine (7-OH), another alkaloid present in the leaf at far lower concentrations, also interacts with that receptor. To clear up the matter, Jonathan A. Javitch, Susruta Majumdar, Dalibor Sames and colleagues set out to probe the pharmacological and metabolic mechanisms behind kratom's analgesic effects.

Through studies in cells and mice, the researchers showed that most of the analgesic effect is from 7-OH rather than mitragynine. They also found that metabolism of mitragynine in mouse and human liver preparations actually produces much more 7-OH than is present naturally in kratom. The team says that the results shed light on some of the seemingly contradictory reports on kratom, but more studies are still needed to see whether their findings in mice extend to humans.
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The authors acknowledge funding from the National Institute on Drug Abuse, the American Kratom Association, the Department of Defense and the Hope for Depression Research Foundation.

The study is freely available as an ACS AuthorChoice article here.

The American Chemical Society, the world's largest scientific society, is a not-for-profit organization chartered by the U.S. Congress. ACS is a global leader in providing access to chemistry-related information and research through its multiple databases, peer-reviewed journals and scientific conferences. ACS does not conduct research, but publishes and publicizes peer-reviewed scientific studies. Its main offices are in Washington, D.C., and Columbus, Ohio.

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