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- Changho Han, Joza Schmitt, and Kristen M Gilliland.
- Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
- Acs Chem Neurosci. 2020 Jan 13.
AbstractThe psychoactive plant kratom is a native plant to Southeast Asia, and its major bioactive alkaloid is mitragynine. Mitragynine exerts its analgesic properties by acting on the opioid receptors. One of its active metabolites, 7-hydroxymytraginine, is found to be 40 times more potent than mitragynine and 10 times more potent than morphine. Interestingly, current research suggests that mitragynine behaves as an atypical opioid agonist, possessing analgesic activity with less severe side effects than those of typical opioids. Although Thailand and Malaysia have criminalized the use, possession, growing, or selling of kratom due to its abuse potential, kratom still remains unregulated in the United States. The U.S. Drug Enforcement Agency (DEA) listed kratom as a "drug of concern" in 2008 with the intent to temporarily place mitragynine and 7-hydroxymitragynine onto Schedule I of the Controlled Substances Act. However, responses from the general public, U.S. Congress, and Kratom Alliances had the DEA retract their intent. Kratom is currently marketed in the United States as a dietary or herbal supplement used to treat chronic pain, anxiety, and depression with over $207 million in annual sales in the United States alone. Here, we will review the traditional and medicinal uses of kratom along with the synthesis of its bioactive ingredients and their pharmacology, metabolism, and structure-activity relationships. The importance in society of this currently controversial substance will also be discussed.
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