Toxicology

Kratom: A Blurb on the Herb

As kratom becomes more ubiquitous in the United States, a growing body of literature calls into question the safety of this herbal supplement.

Case
A 33-year-old male with history of anxiety, depression, and opioid use disorder arrives to the emergency department after witnessed seizure-like activity. He is post-ictal on arrival. Initial workup, including bloodwork and imaging, does not reveal any source of the seizure. As the patient returns to baseline mental status, he states that he has been self-treating his anxiety and opioid use disorder with kratom, a new herbal supplement he bought at a local shop.

What is Kratom?
Kratom derives from Mitragyna speciosa, a plant native to Southeast Asia. Historically it has been used in Thailand and Malaysia for its stimulant properties and purported medicinal benefits.1 Recently, kratom has become popular in the United States for self-treating pain or opioid use disorder. Because of its availability as an herbal supplement, patients perceive kratom as a "safe" alternative to opioids.2

There are more than 25 active alkaloids in kratom. Mitragynine, the primary alkaloid, is less potent than morphine and accounts for about 66% of the total alkaloids in kratom. 7-hydroxymitragynine exists in small concentrations, but is about 46 times more potent than mitragynine.1 Both mitragynine and 7-hydroxymitragynine act on mu-opioid receptors in the same way as heroin or oxycodone. Kratom additionally acts on many other receptors, including alpha-2 receptors, GABA receptors, serotonin receptors, and noradrenergic receptors.2-3 The clinical implications of these interactions are poorly understood.

Why Are People Using Kratom?
Kratom has been used throughout Southeast Asia for centuries as a stimulant for workers trying to combat fatigue associated with manual labor. It is also used medicinally to help with diarrhea, pain relief, morphine withdrawal, and a variety of other ailments.1-4

Kratom's recent popularity in the United States stems primarily from its use as an herbal supplement for self-treating pain or opioid use disorder.4-5 Patients with opioid use disorder face significant barriers that prevent them from accessing evidence-based treatments. This lack of access has caused patients to seek alternatives to medication assisted treatment (methadone or buprenorphine). Kratom is perceived as a "safe" alternative. Not only do patients substitute kratom for their opioids, they also substitute kratom in for antidepressants as well.2

Kratom is readily accessible in local tea shops, smoke shops, gas stations, and on the Internet. Patients can either buy kratom leaves, capsules, or extracts to chew, smoke, or ingest.1-2

What Are the Reported Effects of Kratom?
The effects of kratom are dose dependent, and people generally take a dose tailored to their desired response. White et al.1 found that anecdotally, a low dose, roughly 1-5 g, is reported to produce a mild stimulant effect while a moderate dose, 5-15 g, will produce an opioid-like effect. Large doses, > 15 g, may be very sedating and pose risks similar to heroin or oxycodone overdose. They also report that, due to lack of a scientifically established dose-response curve or quality control measures on kratom packaging, accurate dosing of kratom is difficult and dosing errors are likely.

Kratom is also reported to impact pain, mood, and energy. A survey conducted in 2017 found that almost two-thirds of people stated they use kratom "to relieve negative moods or mental states, including anxiety, depression, and posttraumatic stress".2 The reported effects of kratom have also been described in the mainstream media. In March 2018, Rolling Stone published an article criticizing the United States Drug Enforcement Administration's decision to classify kratom as a schedule I drug and highlighting the anecdotal positive effects reported by people using kratom. The DEA has since removed the schedule I classification and instead classified it as a "drug of concern".1, 4-5

What Are the Adverse and Toxic Effects of Kratom Ingestion?
As kratom use becomes more ubiquitous, a growing body of literature has called into question the safety of this herbal supplement. A recent study of kratom exposures reported to United States Poison Control Centers showed that nearly two-thirds of reported exposures spanning 2011-2017 occurred within the last year of the study window, highlighting its growing popularity.6

Reported adverse effects of kratom include nausea, vomiting, tachycardia, and hypertension. Some of the more serious reported toxicities include seizure, hallucinations, profound sedation, coma, respiratory depression, and neonatal abstinence syndrome.1-2,4,6 Patients using kratom chronically may also experience symptoms of opioid withdrawal when they discontinue usage.

Mortality associated with kratom use has been a point of controversy. Until recently, proponents of kratom have advocated for its use as a safe alternative with minimal overdose risk. However, multiple publications have since reported a growing number of kratom associated fatalities.6 These prompted the FDA to release a report in 2018 detailing 44 deaths associated with kratom use, one of which mitragynine was the only substance detected in post mortem analysis.7 The FDA's report, coupled with growing concerns about kratom toxicities, prompted the Department of Health and Human Services to recommend that the DEA ban kratom use in the United States.

How Do We Manage the Toxic Effects of Kratom?
Toxic effects of kratom should be treated based on the patient's clinical presentation. Swogger et al.2 recommend a symptom-based approach to managing these patients. If opioid-like effects (respiratory depression) are present, naloxone should be administered. Benzodiazepines are recommended for seizures, tachycardia, and hypertension associated with suspected kratom toxicity.

Patients using kratom may also experience symptoms of opioid withdrawal. It is recommended to treat these symptoms similarly to any other type of opioid withdrawal, with evaluation for opioid use disorder, initiation of medication assisted therapy, and referral to treatment as appropriate.8

Why Does Kratom Matter?
Kratom is a widely available herbal supplement that has gained popularity among people looking to self-treat opioid use disorder or pain.1,6 As the opioid epidemic continues to impact millions of people in the United states, it is inevitable that emergency physicians will encounter patients using kratom. It is important that we recognize these clinical effects and treatment strategies so we can appropriately treat and educate this patient population when they present to our EDs. There is a need for additional research on kratom to determine its safety as well as potential effectiveness.

KEY POINTS

  • Kratom mimics opioids. It contains mitragynine, which acts on opioid receptors in the same manner as other prescription or illicit opioids.
  • Kratom's popularity in the United States is on the rise, with patients using it as alternative treatment for pain, opioid use disorder, and mood disorders. Kratom-associated calls to poison control centers are on the rise, even as kratom-associated adverse effects and toxicities are being reported in EDs across the country.
  • Kratom's effects vary widely, and use of this herbal product may lead to significant patient morbidity and mortality.

References
1. White M. Pharmacologic and clinical assessment of kratom. Am J Health-System Pharmacy. 2018;75(5):261-267.
2. Swogger M, Walsh D. Kratom use and mental health: A systematic review. Drug and Alcohol Dependence. 2017;183:134-140.
3. Lydecker A, Sharma A, McCurdy CR, Avery B, Babu K, Boyer E. Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine. J Med Toxicol. 2016;12:341-349.
4. Vestal C. Kratom Concerns. State Legislatures Magazine. 2018; 44(4)
5. Killelea E. Kratom: Why Did the FDA Declare the Herbal Supplement an Opiate? Rolling Stone Magazine. March 2018.
6. Post S, Spiller H, Chounthirath T, Smith G. Kratom exposures reported to United States poison control centers: 2011-2017. Clinical Toxicology.
7. Gershman K, Timm K, Frank M et al. Deaths in Colorado Attributed to Kratom. The New England Journal of Medicine. 2019; 380(1).
8. Gottlieb, S. Statement from FDA Commissioner Scott Gottlieb, M.D., on new warning letters FDA is issuing to companies marketing kratom with unproven medical claims; and the agency’s ongoing concerns about kratom [press release]. Sep 11, 2018.
9. M. Speciosa. Image. https://commons.wikimedia.org/w/index.php?curid=25187129. By ThorPorre - Own work, CC BY 3.0.

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