Kratom in the ED: Pearls and Pitfalls

Author: Brandon M. Carius, DSc, PA-C (Madigan Army Medical Center, Fort Lewis, WA); Brit Long, MD (@long_brit) // Reviewed by: Tony Spadaro, MD, MPH (Assistant Professor of Emergency Medicine, Medical Toxicology, and Addiction Medicine at the University of Pennsylvania); Alex Koyfman, MD (@EMHighAK)

Cases:

#1: A 24-year-old male presents via EMS for concerns of “acting funny”. He was found by his friends at his apartment acutely agitated after “taking some herbal pills that he purchased at a gas station.” He has a prior history of opioid use disorder (OUD) but his friends state that “he’s been off that for a few years”.  His triage vitals are: pulse of 105, blood pressure 100/62, respirations 12, and pulse oximetry of 98% on room air.  As part of the laboratory work-up, a urine drug screen is negative for opiates, benzodiazepines, and methamphetamines. What are your initial thoughts on cause, further evaluation, and management?

#2: A 37-year-old female with a history of fibromyalgia presents due to concerns of a potential new onset of seizure disorder. Her husband states that she seemed be doing well on a new “over-the-counter supplement” that she mixes in her tea multiple times per day to help manage her pain symptoms, but that she abruptly stopped for some reason a couple of days ago.  With the paramedics stabilizing the patient, her husband cannot recall any other medications or supplements she might be taking.  Her vital signs are: pulse of 110, blood pressure of 150/90, respirations at 20, and pulse oximetry of 99% on room air.  What immediate management, evaluation, and disposition should you consider in this patient?

Background

Kratom is a commercially sold, unregulated plant, used across Southeast Asia, parts of the Pacific, and the U.S., creating a small but growing problem for users and medical providers alike. Advertised to ameliorate a variety of conditions, kratom is particularly problematic because of its widespread availability, dose-dependent response, and possible adulteration or co-ingestion with other substances that confound diagnosis. Furthermore, presentations in emergency medicine vary significantly, and can mimic many other substances of abuse.

Kratom (Mitragyna speciosa) is an evergreen tree in the coffee family that originates from Southeast Asia, used as a traditional medicine for generations in that area and investigated for more than 50 years. Initially, workers and laborers, particularly in farming, utilized kratom by chewing on leaves at frequent intervals throughout the day as a natural stimulant. Possibly due to its stimulant and appetite suppressant properties, there is further belief in kratom’s ability to help with a variety of other health conditions, including libido, diabetic hyperglycemia, and hyperlipidemia (Table 1).^1-7 It can be smoked, chewed, or brewed in hot water for tea.^8,9 Additionally, some populations incorporate it regularly in cooking (wrapping of fish, additive to stews and soups).^4,8 Many utilize kratom directly to relieve chronic pain as a compelling alternative to more mainline pharmacotherapy. ^8,10

Consisting of numerous alkaloids, the primary effective compounds in Kratom consist of mitragynine and 7-hydroxy-mitragynine (7-HMG). These alkaloids work as partial m-opioid receptor agonist, and agonist effects at the d, and kopioid receptors, however their concentrations and effects can vary based upon the strain (primarily a sedating “red vein strain” versus a stimulating “white or green vein strain”) used, as well as the age of the plant itself.⁴ Mitragynine is thought to be a biased agonist at the m-opioid receptor, which preferentially activates the downstream G-coupled protein receptor pathway as opposed to the b-arrestin pathway, which is associated with respiratory depression and opioid tolerance, potentially making it a more desirable analgesic than other opioids.^1,11 In older studies, kratom demonstrates less respiratory depression compared to codeine, supporting this often-touted claim amongst people who use kratom.¹²

With perceived health benefits and relatively low risk of side effects from kratom, and increased awareness, the use, misuse, and tracking of kratom increased over the last 25 years. Use estimates within the U.S. currently tracks at up to two million adults annually, although separate estimates report almost three-and-a-half million lifetime users, and these are believed to be underestimates due to underreporting in survey data.^10,13-15 Some estimate annual use may be as high as 10-20 million individuals.^16,17 Relatedly, poison control centers note an increasing trend in calls for concerns of adverse effects and overdose. Whereas there are no significant reports of calls predating 2008, there are sharp increases following this timeframe, including a ten-fold increase in calls to U.S. poison centers between 2010-2015, from 26 to 263 total calls.^18-20 Similarly, while poison control centers recorded 1,807 calls between 2011-2017, almost two-thirds of these calls occurred in the last two years of the study.²¹ Nearly half of poison center calls report concurrent use of kratom with other illicit substances.²⁰

In turn, several nations and American states banned kratom for commercial sale and regular use, with several other states restricting its sale (Table 1). However, due to difficulty with movement across state lines, and commercial internet sales, kratom use remains documented throughout the U.S. ^19,20 After the Drug Enforcement Administration (DEA) attempted to list kratom as a schedule 1 substance in 2016, the initiative stopped and never restarted.¹³ Instead, the DEA relegated kratom to its “Drugs of Concern” registry, with no effect on commercial sales or federal restrictions on use.²² Over the years, numerous issues of abuse, withdrawal, and unrecognized side effect problems are encountered by emergency clinicians within the U.S. Given the prevalence and readily available commercial nature of kratom, it is important for EDs to be able to recognize, identify, and properly manage kratom use, abuse, and withdrawal concerns.

Table 1. Legal restrictions on kratom sale and use in the U.S.**

*States that place requirements for kratom product labels

**As of May 4, 2026 when article was written, regulations subject to change

Background Pearls

• Mitragyna speciosa, the primary ingredient in kratom, traditionally comes from Southeast Asia, is traditionally used for a variety of health concerns, but primarily for stimulant, pain, and metabolic concerns.
• Kratom effects center largely on the impact of two alkaloids, mitragynine and 7-HMG, and are particularly perceived to be desirable for analgesia due to a lack of b-arrestin activation, which decreased risk of respiratory depression.
• Kratom use appears to be escalating sharply over the last 25 years, with subsequent rise in poison control calls, however there are substantial calls with concurrent use of other substances.

Pharmacology

Kratom pharmacology and medicinal profiles rely heavily on its alkaloid composition, and while approximately 45 different alkaloids are identified, the primary ones of interest are mitragynine and 7-HMG.²³ While kratom itself is only 2% 7-HMG, the mitragynine component that makes up 60% of kratom is hepatically metabolized via cytochrome P450 enzymes into 7-HMG.^4,9,24,25 Mitragynine and 7-HMG demonstrate some serotonergic, dopaminergic, and adrenergic receptor activity, but largely function with opioid receptor activation.^15,26 However, it is important to note that repeated studies demonstrate the increased potency of 7-HMG compared to mitragynine and its comparison to other similarly used chemicals. 7-HMG shows more than 40 times the potency of analgesia compared to mitragyinine in isolation.^25-27

The analgesic properties of mitragyinine and 7-HMG appear to be multifactorial. Primarily, both alkaloids demonstrate opioid receptor activity. However, additional works support cyclooxygenase-2 (COX-2) inhibition as well as neuronal calcium channel blocking, which may lead to further analgesic effects.^28,29 Mitragynine is reported to be up to 13 times as strong as morphine in opioid receptor agonism.^9,27 Some classify mitragynine and 7-HMG as ‘atypical opioids’ due to their opioid receptor agonist properties without simultaneous b-arrestin activation.⁸ This is seen, in part, as therefore desirable as users attempt to avoid respiratory depression concerns and more common sedation and constipation side effects of opioids.^8,26,30  It is important to note however, that most of the support and citation behind less b-arrestin activation comes largely from a single 50-year-old study comparing kratom to codeine, therefore with limitations in applicability to more modern opioids and multimodal pharmacologic pain management.¹² A more recent in vivo study of mice with mitragynine-based compounds demonstrated less b-arrestin activation and decreased tolerance compared to morphine.²⁶ Most recently, comparisons of mitragynine to oxycodone in mice did show increased risk of respiratory depression and death, but this occurred in supratherapeutic oxycodone doses of 60 and 150 mg/kg compared to mitragynine and did not demonstrate any difference with dosing at 6.75 mg/kg.³¹

Additional kratom effects with adrenergic and serotonergic receptor activity provide perceived benefit to kratom users, although these are not entirely related to the mitragynine and 7-HMG alkaloids. Rather, unlike mitragynine, the paynantheine and speciogynine alkaloids, amongst others, demonstrate high affinity for serotonin receptors.^23,25,32Similarly, while mitragynine constitutes the largest proportion of alkaloids in kratom, it disproportionately affects adrenergic receptors compared to much smaller quantities of alkaloids that show greater adrenergic affinity, including corynantheidine, ajmalicine, and tetrahydroalstonine.^32,33 The combined effect of blocking serotonin reuptake and stimulating adrenergic receptors is therefore thought to contribute to kratom use for stimulation in work and daily activities.^11,32,34 Kratom demonstrates some potassium channel inhibition as well, which may affect cardiac function, in particular QTc prolongation.³⁵

A dose-dependent effect exists in the use and effects of kratom, primarily with “low dose” and “high dose” pivoting at less than and greater than 5g of plant material, respectively; however “super-high doses” can mimic opioid overdose effects, and similarly, potential complications (Table 2).^{4,10,11,36,37} While not necessarily clear in relation to the differing proportions and effects of its alkaloid constituency, the dose dependent model is traditionally used to differentiate sedating/analgesic from stimulation/alertness objectives.  Onset of kratom effects is generally 10-20 minutes, with peak affects between 2-4 hours after ingestion.^4,9,11,37 Mitragynine and 7-HMG half-life is reported as approximately 3.5 hours and 2.5 hours, respectively.^4,11,37

Table 2. Dose-dependent effects of kratom plant.

Pharmacology Pearls

• Although mitragynine and 7-HMG are the primary alkaloids, mitragynine is largely converted to 7-HMG, which demonstrates much higher analgesic potency.
• While mitragynine and 7-HMG are desired for analgesia without b-arrestin activation, and thus advertised as less respiratory depression, this benefit is largely derived from isolated studies comparing kratom to supratherapeutic doses of opioids.
• Other kratom alkaloids act on serotonergic and adrenergic receptors, which can impact the anxiolytic and stimulant effects, respectively.
• Most literature cites binary “low dose” (less than 5g) and “high dose” (5-15g) effects, but a “super-high dose” (greater than 15g) exists as well.

Current Use

The majority of kratom users appear to be male, between 18-50 years old, and of white ethnicity.^13,14,30 Most users overall report daily ingestion, primarily through a powdered form, for the treatment of chronic pain or depression symptoms, although significant numbers also report kratom use for the treatment or relief of withdrawal symptoms related to discontinuation or decreased use of opioids.^30,38,39 This became particularly important during the COVID-19 era with a confluence of post-COVID symptoms such as pain and a general lack of energy.^16,36

While there are several traditional uses for incorporating kratom into daily use, more recently there have been several vehicles for more direct recreational use, and potential abuse. These include attempts by users to increase the potency, delivery, and additive effects of kratom. These “enhancements” span from the relatively simple addition of lemon juice to enhance intestinal absorption, to a “kratom cocktail” involving mixing leaves with liquid diphenhydramine, or the addition potent and caustic chemical additives.^{7,9,11,15,40,41} Southeast Asia is creating increased social demand for kratom preparations and experimentation, including a beverage concoction of kratom, cough syrup, Coca-Cola, and ice, known as “4×100”, as well as other preparations including benzodiazepines, fluorescent tubes, road paint, and pesticides.^7,9,40,41

Similarly, difficulty exists with separating the effects of kratom use from recreational polypharmacy. People who use kratom users generally reports significant co-ingestion or concurrent use of a variety of substances of abuse.^13,14,18 This includes significant correlation to use or misuse of cocaine, cannabis, benzodiazepines, and prescription stimulants.^9,14,18,38 There is overlap of patients who use kratom and patients with OUD, many patients with OUD may use kratom to self-treat symptoms of opioid withdrawal.⁴²

Initial Assessment

Patients presenting to the ED for kratom use, both acute and chronic, as well as withdrawal, pose a significant challenge due to its unregulated production, vast commercial distribution, wide-ranging side effects, and high potential for co-ingestion, either intentional or unintentional. Initial assessment and suspicion for kratom involvement is based on stated history of use by the patient or their proxies, rather than any pathognomonic findings.

Patients may present after acute ingestion may appear similar to an opioid toxidrome with miosis and sedation but patients can also appear acutely agitated, or with hallucinations, nausea, vomiting, or diarrhea.^8,19,22,43 Patients with regular chronic use may present for non-specific symptoms, such as fatigue, nausea, constipation, and insomnia.^8,9 Given the stimulant nature of kratom, especially in the low-dose range, presentations for acute ingestion may demonstrate tachycardia on initial assessment, but is not consistently found in most of the case report literature.^19,20,44 Likewise, remaining vital signs are generally stable. However, the issue of significant co-ingestion can create difficulties in the initial assessment. Reported cases of acute ingestion resulting in seizure-like activity or otherwise being “found down” are difficult to interpret in attributing presentation solely to kratom ingestion, although a single case of isolate kratom use with seizure does exist in the literature.^{10,15,35,44-46} However, in a case series of 95 instances of kratom overdose, a total of 92 cases involved the use of 15 categories of ‘confounding substance’ co-ingestants, with more than half of these cases involving benzodiazepines, SSRIs, opioids, and antipsychotics.¹⁵

The attempt to decrease or completely cease kratom use, can create a constellation of symptoms similar to withdrawal of other substances, but primarily mimicking opioid withdrawal.^7,22,47 Patients with kratom withdrawal may complain of abdominal cramping, body aches, insomnia, profuse sweating, vision changes, nausea, vomiting, and diarrhea.^{4,22,36,47,48} These symptoms may present within the first 12-24 hours from cessation of chronic use, but the window of symptom onset may be as long as seven days.⁴⁷ Patients in kratom withdrawal can present with mild tachycardia, as well as hypertension and fever.^47,49

Diagnostic evaluation is largely dependent on targeting the most severe outcomes of kratom use, but is rarely consistent across literature.⁴⁴ Most notably the urine drug screen, does not detect for kratom or its constituent alkaloids.^10,44,47,49 The finding of other substances can be further confounding, as they can be co-ingestants, adulterants in varying concentration, or reflecting distant past use.^1,18 Rather, identification of kratom requires liquid chromatography or ion mass spectrometry, which will not result in a clinically relevant time frame for emergency medicine clinicians.^4,9,37,47,49Case reports demonstrating laboratory abnormalities include a wide range of findings attributed to kratom use, including rhabdomyolysis, liver injury, and cardiotoxicity.^{22,35,37,44,45,50} Electrolyte abnormalities include both hypokalemia and hyperkalemia, and elevated serum creatinine, creatinine kinase, bilirubin, and liver enzymes.^35,45,46 Generally, hyperkalemia and serum creatinine elevations follow high creatinine kinase in rhabdomyolysis cases.^45,46 Multiple cases of cholestatic liver injury demonstrate a transaminitis pattern, without discernable elevation in any specific enzyme.⁵⁰ In these cases, however, hyperbilirubinemia is generally profound.^50,51 Dysrhythmias are found in the literature, primarily with documented instances of Brugada pattern, QTc prolongation (as high as 654 msec), and documentation of new-onset severe congestive heart failure.^1,22,35,45

Assessment Pearls

• Kratom use presentation is focused on individual symptom complaint rather than “classic” or pathognomonic history. Use is almost entirely based on volunteered history.
• Kratom overdose can present with seizure-like activity or being “found down”, although clinicians should note that there is often co-ingestion of other substances that may be contributory. Kratom withdrawal can largely mimic opioid withdrawal symptoms.
• Initial evaluation includes basic laboratory testing and ECG, however standard urine drug screening does not test for kratom, and therefore must be deliberately tested via liquid chromatography or ion mass spectrometry.

Management

There are no published consensus or other proposed guidelines for the management of kratom use or withdrawal in the ED setting. Published commentary on management primarily comes from case reports, case series, or other reviews. Initial management of kratom use cases centers on symptomatic presentation rather than substance-specific treatment.  Clinicians should promptly and continuously assess for signs of acute agitation in the setting of acute or chronic use or suspected withdrawal. This is especially critical in populations where initial vital signs may initially prove to be falsely reassuring despite overall clinical presentation of ill appearance or excitation.

Initial management includes ensuring proper airway patency and adequate circulation. If respiratory depression is present, naloxone should be considered, especially given the prevalence of co-ingestion with opioids.^8,43 In cases of acute or chronic ingestion with tachycardia, it is reasonable to empirically initiate intravenous isotonic fluid resuscitation both in terms of initial cardiovascular support as well as early management for the potential for rhabdomyolysis. Although documented cases of blood glucose testing with kratom use presentations in the literature reveal no instances of hypoglycemia, cases of agitation, altered mental status, or seizure presentation, even with known kratom ingestion, should evaluate blood sugar since kratom is employed often as an appetite suppressant.^10,49 As with other agitated or altered patients, laboratory evaluation should likewise include CBC, BMP, liver function panel, and urinalysis, and a non-contrast head CT should be considered. ECG should be obtained to evaluate for possible dysrhythmias and QTc prolongation.

Documented cases of seizure presentation with suspected kratom overdose cites the use of benzodiazepines, levetiracetam, and ultimately sedation with propofol, fentanyl, and dexmedetomidine with intubation for status epilepticus.^10,44 QTc prolongation should initially be managed by correcting any underlying electrolyte abnormalities, and avoidance of other QTc prolongation medication, however a single case report describes initial use of sodium bicarbonate with QTc suspected from kratom use.^35,44

Suspected kratom withdrawal in the ED is management based on the severity of presentation. Mild agitation or withdrawal symptoms can be considered for supportive outpatient management with hydroxyzine, benzodiazepines, or clonidine in with close follow-up.^4,47,49 However, it is important to note that case reports do not validate any successful cases of cessation, rather hospitalization for outpatient treatment failure.^4,10,49 While there is no established regimen for buprenorphine initiation in the setting of kratom withdrawal, prior literature discusses using the Clinical Opioid Withdrawal Scale (COWS), and buprenorphine can be started at a 4-8mg dose.^4,49 Patients who fulfill criteria for substance use disorder (tolerance, withdrawal, uncontrolled use, and continued use despite negative consequence) are reasonable candidates for buprenorphine initiation, however they should also be closely followed in the outpatient setting by either primary care, addiction medicine, or psychiatric care. Clonidine may help with kratom withdrawal specifically due to its alpha-2 agonist properties, although no clinical trials are published at this time.^8,22,47,49

Consider consulting with a local toxicologist or regional poison center (1-800-222-1222) to help with the management of kratom intoxication, withdrawal, or if other co-ingestions are suspected. Regional poison centers may track calls related to kratom, perform public health surveillance, and could alert local officials if there appears to be a cluster of cases related to particular kratom formulations.

Management Pearls

• Initial emergency management largely centers on a approach to treating abnormal findings on initial assessment, primarily tachycardia.
• Any respiratory depression concerns should be treated with empiric naloxone administration.
• Clinicians should anticipate electrolyte abnormalities and potential dysrhythmias, with management focusing on derangement correction, particularly in instances of QTc prolongation.
• While multiple medications can be considered for management of withdrawal symptoms, literature is still evolving on the optimal treatment, consider symptomatic management with hydroxyzine, benzos, buprenorphine.

Disposition

Disposition from the ED is based largely on the reason for presentation. Kratom users with acute ingestion and unremarkable evaluation, not seeking to cease consumption, can be considered for discharge home. However, even with a reassuring overall clinical presentation, patients with seizure concerns precipitated by kratom use or withdrawal should be considered for admission. Those with complications from use, to include rhabdomyolysis, acute agitation or altered mental status, or cardiotoxicity side effects related to kratom use should likewise be admitted for evaluation and monitoring, especially given the potential window for withdrawal during hospitalization.

Case Resolution

Case #1: After further discussion with the patient’s friends, you find that the patient has been ingesting kratom purchased from a local gas station. You initially stabilize the patient with IV fluids, and supportive medications. His laboratory evaluation comes back notable for a CK of greater than 10,000, an elevated serum creatinine at 1.5 mg/dL, and myoglobinuria, indicating rhabdomyolysis. Thankfully, he has no significant electrolyte derangements or ECG abnormalities. A non-contrast head CT shows no abnormal findings. During his ED stay, you initiate IV fluids, and when he has an episode of acute agitation, it is managed well with 1mg of IV lorazepam. You consult with the hospitalist, who agrees for admission for continued observation and monitoring of the rhabdomyolysis, which psychiatric consultation for detox resourcing.

Case #2: You initially stabilize the patient in the resuscitation bay, however she suffers another tonic-clonic seizure, which abates after 1mg IV lorazepam is giving, and therefore you initiate a levetiracetam load. Laboratory evaluation does not demonstrate any electrolyte abnormalities, and ECG is unremarkable for dysrhythmia. After the urine drug screen returns without findings, you remember that you need special testing for kratom, and ion mass spectrometry confirms suspected kratom use. CT evaluation is negative for any significant hemorrhage, mass, or midline shift. With no other findings, and repeated witnessed seizure activity, you consult neurology and hospitalist, and the patient is admitted for EEG, continued monitoring, and inpatient initiation of kratom withdrawal with clonidine.

Disclaimer: The view(s) expressed herein are those of the author(s) and do not reflect the official policy or position of Madigan Army Medical Center, the U.S. Army Medical Department, the U.S. Army Office of the Surgeon General, the Department of the Army, or the Department of Defense or the U.S. Government.

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