Yen Nien Hou, PharmD, DipIOM, LAc
Jyothirmai Gubili, MS
The ASCO Post’s Integrative Oncology series is intended to facilitate the availability of evidence-based information on integrative and complementary therapies sometimes used by patients with cancer. In this installment, Yen Nien Hou, PharmD, DipIOM, LAc, and Jyothirmai Gubili, MS, focus on kratom—an herbal extract from a Southeast Asian tropical tree in the coffee family with a high potential for abuse—because of its increasing popularity as a pain reliever.
Scientific Name: Mitragyna speciosa
Common Names: Cratom, Ketum, Kakuam, Biak, Mitragyna, Mitragynine, Thang, Thom
Overview
A tropical tree prevalent in Southeast Asia, kratom has a long history of medicinal use. Its leaves are chewed, smoked, or used to make tea for stimulant effects. They are also used for wound healing, to relieve diarrhea, to reduce pain and fever, and as a substitute for opium. Kratom has recently gained popularity in the United States as a pain reliever, a mood enhancer, and as an alternative for treating opioid withdrawal. However, its use has been associated with severe adverse effects, along with a high potential for abuse. Kratom is banned in several states in the United States and in some countries.
The U.S. Food and Drug Administration (FDA) has also recently warned companies marketing kratom with false claims of preventing or treating COVID-19 infection.1
The Science
Preclinical studies have shown that kratom has muscle relaxant,2 anti-inflammatory,3 analgesic,4 anorectic,5 and morphine-like6 effects.
Clinical data on kratom are limited. Kratom was reported to exert stimulant effects at low doses (1–5 g), whereas pain-relieving and sedative properties were observed at higher doses (5–15 g).7 These effects occur within 5 to 10 minutes after ingestion and may persist for 2 to 5 hours.8
Pharmacologic studies found the alkaloids mitragynine and 7-hydroxymitragynine to be the chief bioactive compounds.9 Both produce central nervous system stimulant and depressant effects via monoaminergic and opioid receptors.10,11 They also mimic opioids, as evidenced by their affinity for opioid receptors, competitive interaction with naloxone (a medication used to reverse opioid overdose), as well as analgesic cross-tolerance.12 In addition, mitragynine can cause addiction profiles similar to those of morphine and cognitive impairment.13
Adverse Reactions
Symptoms associated with kratom withdrawal include nausea, vomiting, chills, sweats, muscle spasms and pain, decreased appetite, diarrhea, anxiety, irritability, depressed mood, hot flashes, and sleeping difficulty.14-16
Liver injury has been reported following prolonged use of kratom.17-19
Cardiotoxicity was observed as a result of ingesting kratom.20-22
Several deaths have been associated with the use of kratom-containing products or polydrug use in which kratom was believed to play a role.23-31
Herb-Drug Interactions
Cytochrome P450 (CYP450) Substrates: There is a potential for increased clearance of drugs metabolized by CYP450 substrates in kratom users.32,33 Kratom may also inhibit CYP2D634 and induce CYP1A2.35
UGT (uridine 5’-diphospho-glucuronosyltransferase) Substrates: There is also potential for increased clearance of drugs metabolized by UGT1A6 with kratom use.32
P-glycoprotein Substrates: Mitragynine inhibits P-glycoprotein in vitro. Therefore, simultaneous administration of mitragynine with psychoactive drugs that are P-glycoprotein substrates may cause severe toxicity.36
Summary
Kratom is a controversial agent whose physiologic effects have yet to be fully characterized. It was placed on the “drugs of concern” list by the Drug Enforcement Administration37 and labeled as an “emerging drug of abuse” by the National Institute of Drug Abuse.38 Also, the FDA issued a public health advisory against its use, citing the potential for abuse.23 Despite these warnings, kratom continues to be widely marketed on the Internet.
Guest Editor
Jun J. Mao, MD, MSCE
Integrative Oncology is guest edited by Jun J. Mao, MD, MSCE, Laurance S. Rockefeller Chair in Integrative Medicine and Chief of Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.
It is critical for health-care providers to be familiar with kratom. Suggested strategies for managing patients who abuse kratom include prevention of organ damage, alleviation of acute kratom withdrawal symptoms, and long-term maintenance of sobriety.39
DISCLOSURE: Dr. Hou and Ms. Gubili reported no conflicts of interest.
REFERENCES
1. U.S. Food and Drug Administration: The Golden Road Kratom. May 15, 2020. Available at https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/golden-road-kratom-607627-05152020. Accessed on February 9, 2021.
2. Chittrakarn S, Keawpradub N, Sawangjaroen K, et al. The neuromuscular blockade produced by pure alkaloid, mitragynine and methanol extract of kratom leaves (Mitragyna speciosa Korth.). J Ethnopharmacol 129:344-349, 2010.
3. Shaik Mossadeq WM, Sulaiman MR, Tengku Mohamad TA, et al: Anti-inflammatory and antinociceptive effects of Mitragyna speciosa Korth methanolic extract. Med Princ Pract 18:378-384, 2009.
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28. Anwar M, Law R, Schier J: Notes from the field: Kratom (Mitragyna speciosa) exposures reported to poison venters – United States, 2010–2015. MMWR Morb Mortal Wkly Rep 65:748-749, 2016.
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32. Azizi J, Ismail S, Mansor SM: Mitragyna speciosa Korth leaves extracts induced the CYP450 catalyzed aminopyrine-N-demethylase (APND) and UDP-glucuronosyl transferase (UGT) activities in male Sprague-Dawley rat livers. Drug Metabol Drug Interact 28:95-105, 2013.
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38. National Institute on Drug Abuse: Kratom Drug Facts. Available at https://www.drugabuse.gov/publications/drugfacts/kratom. Accessed February 9, 2021.
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Dr. Hou is Manager of the “About Herbs” website, maintained by Memorial Sloan Kettering Cancer Center’s Integrative Medicine Service, and Ms. Gubili is Editor, both at the Integrative Medicine Service, Memorial Sloan Kettering Cancer Center, New York.
