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Pharmacology 101: Kratom, Part 1
There’s a gas station I pass nearly every day that has a sandwich board advertising kratom for sale. It looks innocuous, just a simple sold here sign in big bold letters. But what is kratom? The astute reader might surmise it perhaps has some pharmacological properties (the title of this column being a bit of a giveaway), so I’ll give you the short answer up front: Kratom is a species of tree (Mitragyna speciosa) with compounds that interact with opioid receptors, as well as adrenergic, serotonergic, and adenosine receptors.
Now for a deeper dive: What is kratom? How does it work? What is it used for? Is it legal? What are its side effects?
The Basics
Kratom (also called thang, kakuam, thom, ketum, and biak) is an indigenous tropical plant species from Southeast Asia with a unique pharmacological profile. The leaves may be chewed, steeped into tea, or dried and crushed into powder before being used to make capsules or gel formulations. Another method of preparation involves kratom juice, via boiling the leaves until they emit a strong smell; the juice is then consumed either warmed or chilled.1
Kratom’s two main active compounds are mitragynine and 7-hydroxymitragynine. It has energizing, psychostimulant, and pain-relieving effects, with an apparent dose-response curve: stimulation at lower doses (1–5 g), opioidlike characteristics at higher doses (5–15 g), and sedative effects at very high doses (more than 15 g).1–4 While it does interact with opioid receptors, compared to traditional opioid agonists, kratom has less-intense euphoric effects.5,6
Kratom has been used for centuries in Southeast Asia but has more recently gained popularity and attention in the United States. Kratom may be sought for its perceived therapeutic effects or recreational purposes, and in addition to being sold in head shops, gas stations, and kava bars, it is widely available on the internet.1,6
Reasons for taking kratom include enhancing physical energy, for mental or emotional conditions (eg, anxiety, depression, or PTSD), to overcome fatigue, and to treat medical problems such as diabetes and chronic pain.1,7 Additionally, substance dependence is a notable purpose for which people have reported taking kratom. Identified more than 100 years ago for its potential in treating opioid addiction, kratom’s historical use to ease opioid withdrawal symptoms has continued into modern times.2,5,6 Users may also take it to help control alcohol withdrawal effects and chronic pain.6
One survey published in Addiction in 2021 reported results showing that past-year kratom use in the adult US population was 0.8%.2 In 2016 the American Kratom Association’s executive director was reported to have said he believed 4–5 million Americans may be using kratom.8
A 2017 kratom use survey conducted online with more than 8000 respondents showed most tended to be Caucasian (89%), males (57%), aged 31–50 (55%), with incomes over $35,000 per year (63%), gainfully employed (56%), with private or self-insurance (61%) and at least some college education (82%). Fifty-six percent reported use lasting 1–5 years. Forty percent said they discussed their use of kratom with their healthcare provider.7
Legal Status
In 2016 the DEA announced it intended to classify kratom as a Schedule I compound, a category of substances with no currently accepted medical use and a high potential for abuse. The announcement produced pushback from the public, and the DEA reversed its plan. Currently kratom is not controlled under the Controlled Substances Act, although some states or localities may have narrower regulations regarding its use.5 For example, at the time of this writing, Kansas is considering HB 2056, a bill aimed at regulating kratom in that state.9
The FDA maintains a webpage “warning consumers not to use Mitragyna speciosa” and going on to caution that “FDA is concerned that kratom, which affects the same opioid brain receptors as morphine, appears to have properties that expose users to the risks of addiction, abuse, and dependence.” There are no FDA-approved uses for kratom at this time.
In addition to making requests over the years for US marshals to seize products containing kratom, the FDA has also issued warning letters to companies selling unapproved products with unproven claims about their ability to cure or treat various ailments, including opioid addiction and withdrawal symptoms.
The second part of this article will explore the pharmacokinetics of kratom, as well as risks and adverse events associated with its use, and future research directions.
The views and opinions expressed in this article are those of the author.
References
1. Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend. 2014; 139: 132–7. doi:10.1016/j.drugalcdep.2014.03.017
2. Schimmel J, Amioka E, Rockhill K, et al. Prevalence and description of kratom (Mitragyna speciosa) use in the United States: a cross-sectional study. Addiction. 2021; 116(1): 176–81. doi:10.1111/add.15082
3. Eastlack SC, Cornett EM, Kaye AD. Kratom—Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review. Pain Ther. 2020; 9(1): 55–69. doi:10.1007/s40122-020-00151-x
4. Post S, Spiller HA, Chounthirath T, Smith GA. Kratom exposures reported to United States poison control centers: 2011–2017. Clin Toxicol. 2019; 57(10): 847–54. doi:10.1080/15563650.2019.1569236
5. White CM. Pharmacologic and clinical assessment of kratom: An update. Am J Heal Pharm. 2019; 76(23): 1915–25. doi:10.1093/ajhp/zxz221
6. Warner ML, Kaufman NC, Grundmann O. The pharmacology and toxicology of kratom: from traditional herb to drug of abuse. Int J Legal Med. 2016; 130(1): 127–38. doi:10.1007/s00414-015-1279-y
7. Grundmann O. Patterns of Kratom use and health impact in the US—Results from an online survey. Drug Alcohol Depend. 2017; 176(March): 63–70. doi:10.1016/j.drugalcdep.2017.03.007
8. Nelson S. Dozens of Congressmen Ask DEA Not to Ban Kratom Next Week. US News & World Report. Published September 23, 2016. Accessed March 8. 2022. www.usnews.com/news/articles/2016-09-23/45-congressmen-ask-dea-not-to-ban-kratom-next-week
9. Chung R. ‘War on Kratom’ sparks push for protection in Kansas. Fox4. Published January 22, 2022. Accessed March 8, 2022. https://fox4kc.com/news/war-on-kratom-sparks-push-for-protection-in-kansas/.
Daniel Hu, PharmD, BCCCP, has Doctor of Pharmacy degree and is a critical care and emergency medicine pharmacist. He is a frequent speaker at conferences and has many publications in peer-reviewed journals.
