Kratom, a Legal Drug of Abuse

Why users might be coming to an ED near you.

Intro: Kratom is an old drug that has made a new appearance on the recreational drug scene in the last few years. It is derived from the mitragyna speciose plant found in Southeast Asia, and has been used in its native areas for personal use, as a traditional remedy and in religious ceremonies for centuries. Over the last few years, kratom has made its way to the West.[1] At lower doses it has stimulant effects, and at higher doses it has opioid-like effects. Here we present what ED clinicians needs to know about kratom.

Recreational Use:

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Kratom cannot be legally sold as a medicinal agent, but is frequently marketed as a natural remedy or dietary supplement. It is sometimes sold in packets that are labeled “not for human consumption,” harkening back to similar packaging used on bath salts before they were regulated. It is easily obtained online or purchased in some smoke shops. Kratom is typically taken orally in pill form, or the leaves can be chewed, smoked, or made into a tea.

Some people use it purely recreationally, while others use it to treat their pain, depression, diarrhea or opioid withdrawal symptoms. Tolerance often develops rapidly, leading to persistent use in escalating amounts.  Unfortunately, there have been deaths associated with kratom use. Most of the deaths have occurred in conjunction with use of other medications, drugs abuse or alcohol.[^2,3]

The most common co-ingestants that have led to death are benzodiazepines, opioids and gabapentin, which is often used with kratom to enhance the opioid-like euphoria. However, at least one death was attributed solely to kratom use.

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It has many of the same side effects of opioids, such as nausea, itching and constipation, but can also cause psychosis, hallucinations and the final common lethal pathway of many toxidromes: seizure, coma and death.[^4] Patients may present from kratom overdose or side effects, or could present from withdrawal symptoms such as irritability, myalgias, rhinorrhea and aggression. A case of neonatal withdrawal symptoms have also been reported in an infant born to a chronic kratom user.[^5]

How it works:

There are two main compounds that have opioid agonist effects, mytraginine and 7-alpha-hydroxymitragynine. These chemicals cause the typical opioid effects of sedation, pain reduction and pleasure, particularly when large quantities are used.

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Mytraginine interacts with additional receptors in the brain to produce stimulant effects. The full chemical makeup of kratom leaves is not understood and since it is a plant-based product, there are many different chemicals present.

Presentation and management:

Kratom is known under many different colloquial names, including Thang, Kakuam, Thom, Ketum, Krypton, Ketum and Thom, among others. Unfortunately there are no specific signs and symptoms, and no diagnostic studies to confirm or rule out kratom use, and treatment is supportive.

The half-lives of the active species are 2.5 to 3.5 hours.[^6] Low doses of 1-5g typically result in symptoms from the stimulant effects, such as increased alertness, energy, and talkativeness, but also side effects of anxiety, agitation, itching and nausea.

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At the higher doses of 5-15g of the dried leaves, the opiate-like effects are more prevalent, mild euphoria but also constipation, hypotension, dizziness, dry mouth, and diaphoresis. At doses over 15g, patients can develop stupor and respiratory depression. Chronic, heavy users can develop tremors, seizures, psychosis, and anorexia.[^6]

Recently in the news for:

Both the FDA and the DEA have raised serious concerns about kratom and are looking into restricting its use. As early as 2013, the DEA released a statement that “there is no legitimate medical use for kratom.”[^6] In 1943 it became illegal to plant trees in Thailand, where it grows endemically.

In 1979, it was classified as a Category V drug in Thailand, and it has also been listed as a controlled substance in many other countries. In 2016, the DEA had planned to list kratom as a Schedule I controlled substance, akin to heroin. However there was backlash from kratom advocates, and the plan was withdrawn. The FDA has also cited concerns over its safety and the lack of evidence that it is safe for treatment of opioid withdrawal. The FDA issued a mandatory recall of some kratom products in 2018 due to salmonella contamination. The American Kratom Association solicits help from “Kratom Warriors” to join the “Kratom Truth Squad” and oppose the DEA’s and the FDA’s efforts to restrict kratom.[^7]

Cost:

Kratom can be purchased online as the dried leaves for about $13 for 30g.

Take home points:

Kratom is readily and widely available in the US, with a strong lobby for its continued legalization. If a patient presents to the ED and reports taking kratom, the effects may vary from mild stimulant effects to opioid effects and respiratory suppression, particularly if co-ingested with other substances. Kratom will not show up as a positive on urine drug screens. Be aware that patients may try to treat their pain or opioid withdrawal symptoms with kratom.

Unfortunately, case reports from the American Association of Poison Control Centers suggest that respiratory depression from kratom overdose may not respond to typical reversal agents such as naloxone. Withdrawal symptoms can occur on cessation of kratom use, and are similar to opioid withdrawal symptoms. Kratom withdrawal can be treated with the same supportive measures and medications as opioid withdrawal.

Armed with this knowledge, keep an eye out for this new “herbal remedy” and potential symptoms of overdose or withdrawal. The kratom craze could be coming to an ED near you![^8]

References:

1. Rech MA, Donahey E, Cappiello Dziedzic JM, Oh L, Greenhalgh E. New Drugs of Abuse. Pharmacother J Hum Pharmacol Drug Ther. 2015;35(2):189-197. doi:10.1002/phar.1522.
2. Aggarwal G, Robertson E, McKinlay J, Walter E. Death from Kratom toxicity and the possible role of intralipid. J Intensive Care Soc. 2018;19(1):61-63. doi:10.1177/1751143717712652.
3. Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol. 2011;35(4):242-247. http://www.ncbi.nlm.nih.gov/pubmed/21513619. Accessed October 17, 2018.
4. Chang-Chien GC, Odonkor CA, Amorapanth P. Is Kratom the New “Legal High” on the Block?: The Case of an Emerging Opioid Receptor Agonist with Substance Abuse Potential. Pain Physician. 20(1):E195-E198. http://www.ncbi.nlm.nih.gov/pubmed/28072812. Accessed October 17, 2018.
5. Davidson L, Rawat M, Stojanovski S, Chandrasekharan P. Natural drugs, not so natural effects: Neonatal abstinence syndrome secondary to “kratom”. J Neonatal Perinatal Med. August 2018:1-4. doi:10.3233/NPM-1863.
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):127-138. doi:10.1007/s00414-015-1279-y.
7. Office of Diversion Control D. KRATOM (Mitragyna Speciosa Korth) (Street Names: Thang, Kakuam, Thom, Ketum, Biak). https://www.deadiversion.usdoj.gov/drug_chem_info/kratom.pdf. Accessed October 17, 2018.
8. No Title. www.americankratomassociation.org.
9. Kratom Craze Begins to Emerge in U.S. https://www.drugaddictiontreatment.com/types-of-addiction/designer-drugs/kratom-craze-begins-to-emerge-in-u-s/. Accessed October 17, 2018.