Version July 2025
INTRODUCTION —
Kratom (Mitragyna speciosa) is a natural product derived from a tree native to Southeast Asia. Kratom has been used for centuries in Malaysia and Thailand for its stimulant, analgesic, and antidepressant properties, where it is commonly known as 'thang," "kakuam," "thom," "ketum," and "biak" [1,2]. In countries outside of Southeast Asia, kratom is used primarily as a remedy for chronic pain, self-treatment for opioid withdrawal, or in the setting of polysubstance use. Kratom is associated with acute adverse effects as well as dependence with chronic use [3].
Although this topic focuses on natural kratom leaf products in a patient who presents for care following kratom use, clinical effects may be confounded by the presence of coingested medications, particularly opioids and sedative-hypnotics; adulteration of kratom products with psychoactive substances; inadequacy of laboratory testing; or the presence of withdrawal syndromes.
This topic will discuss the evaluation and management of poisoning and adverse health effects in patients who use kratom. The following related content is discussed separately:
●The evaluation and management of the poisoned patient (see "General approach to drug poisoning in adults" and "Approach to the child with occult toxic exposure" and "Initial management of the critically ill adult with an unknown overdose")
●Management of adult patient with agitation (see "The acutely agitated or violent adult: Overview, assessment, and nonpharmacologic management" and "The acutely agitated or violent adult: Pharmacologic management")
●Management of opioid intoxication (see "Acute opioid intoxication in adults" and "Opioid intoxication in children and adolescents")
●Management of opioid withdrawal (see "Opioid withdrawal: Clinical features, assessment, and diagnosis" and "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder" and "Opioid withdrawal in adults in the emergency setting" and "Opioid withdrawal in adolescents")
●Management of opioid use disorder (see "Opioid use disorder: Treatment overview" and "Opioid use disorder: Epidemiology, clinical features, health consequences, screening, and assessment" and "Opioid use disorder: Pharmacologic management")
EPIDEMIOLOGY —
In the United States (US), an estimated 10 to 16 million people use kratom with a prevalence between 1.3 and 6.1 percent; national survey data likely underestimates regular use prevalence [4-6]. In a study that surveyed almost 60,000 US adults in 2018 to 2019, the past-year and lifetime prevalence of kratom use were 0.8 and 1.3 percent, respectively [7]. Young males (mean age 35 years) were the predominant demographic to use kratom.
There were 1807 kratom exposures reported to US poison centers between 2011 and 2017 [8]. Among cases in which kratom was identified as the primary exposure, 32 percent were admitted to a health care facility. There were 11 deaths reported, including nine individuals with polysubstance exposures and two who purportedly had isolated kratom exposure. In another US poison center study between 2014 to 2019, older adults (age >60 years) accounted for 5 percent of kratom exposures with 23 deaths (14 percent) associated with use of the herb [9]. Poison center data, however, typically underestimates prevalence of toxicity since reporting is voluntary, routine laboratory testing cannot identify mitragynine and often is inadequate to identify many opioid analgesics and other coingestants, and many individuals who use kratom do not have substantial adverse events and thus do not seek medical care.
In Thailand and Malaysia, younger individuals drink cocktails known as "4x100" for the neuropsychiatric properties and to replace alcohol; these typically contain kratom, cough syrup (with either diphenhydramine or codeine), and cola [10].
REGULATION OF KRATOM —
Kratom is prohibited in some countries and some states in the United States (US). It is listed as a Drug and Chemical of Concern by the US Drug Enforcement Agency. The US Food and Drug Administration (FDA) has not approved kratom for any medical use and has issued multiple advisories on health risks with its use for opioid withdrawal [11,12], as well as its association with a multistate Salmonella outbreak in 2018 leading to a mandatory recall of kratom-containing products processed by Triangle Pharmanaturals, LLC [13,14].
Kratom products can be purchased widely in the US. In a 2023 survey of 520 US tobacco specialty stores, 72 percent reported selling kratom products (80 percent in the 46 states and territories without kratom bans) [15].
No standards for kratom production and content exist. The American Kratom Association has recommended that manufacturers should voluntarily adhere to testing and purity standards [16]. Commercially sold kratom products likely have alkaloidal concentrations that are different compared with natural leaf products, as well as potential adulterants.
PHARMACOLOGY
Neurobehavioral effects — The neurobehavioral effects of kratom are more subtle than the commonly described stimulant effects at low doses and opioid effects at higher doses [3]. Low doses of kratom (ie, 1 to 4 grams) increase alertness, energy, and talkativeness. At kratom doses greater than 5 grams, however, users describe the persistence of heightened alertness coupled with analgesia (or control of opioid withdrawal symptoms) [17,18].
Effects begin 5 to 10 minutes after consuming kratom tea and typically last for one hour [19,20].
Route of use — In traditional settings, kratom leaves are crushed, boiled, and filtered to produce a "juice" that is then diluted with hot water. In nontraditional use, leaves are dried and ground into a powder that is then brewed with tea, packaged into capsules, or reformulated into gel caps, tablets, extracts, or gummies [2]. Hot water extraction of commercial kratom tea bag products may provide lower alkaloidal doses compared with other formulations [21]. Injection of extract in profound use has been reported [22].
Alkaloids (eg, mitragynine) — Mitragynine is the most prevalent alkaloid in kratom. The kratom plant also elaborates dozens of other naturally produced alkaloids, including paynantheine, speciociliatine, and speciogynine [23-29].
●Mitragynine – This is the most abundant alkaloid in the kratom plant and has a chemical structure similar to yohimbine [30]. Mitragynine, despite having a different chemical structure compared with traditional opioids, primarily binds at the mu-opioid receptor (MOR) where it is a weak opioid agonist with lower potency than morphine [20,31]. Mitragynine is a "biased" ligand that induces many of the effects associated with MOR binding, but does not produce euphoria and respiratory effects to the same degree as classic MOR agonists such as morphine. Mitragynine is a partial agonist at supraspinal MOR as well as delta-opioid, serotonergic, and noradrenergic receptors. It is also an agonist at alpha-2 adrenergic receptors [32-35]. In animal studies, mitragynine has a ceiling effect on respiratory depression and conversion to the active metabolite appears to have saturable kinetics [36].
One laboratory study found that mitragynine was listed as a "primary toxicologic finding" (as opposed to cause of death) when present at concentrations greater than 1000 nanogram/mL, but studies involving live human participants found that mitragynine concentrations over 22,000 nanogram/mL produced no respiratory or cardiac effects [37,38].
●7-hydroxymitragynine – This alkaloid is the active metabolite of mitragynine [39]. Although 7-hydroxymitragynine is 46 and 13 times more potent than mitragynine and morphine at the MOR, respectively, the small amounts produced by metabolism may be insufficient to exert significant clinical effects [35,36,40,41]. 7-hydroxymitragynine demonstrates little effect at alpha adrenergic receptors. Naturally-occurring kratom plant products contain low 7-hydroxymitragynine concentrations. Some commercial products contain 7-hydroxymitragynine concentrations that are greater (eg, three- to fivefold) than would be expected than if derived naturally, suggesting adulteration of the formulation [42]. Beverages and other food products (eg, gummies) containing 7-hydroxymitragynine as the sole psychoactive ingredient are also commercially available.
●Speciociliatine – This diastereomer of mitragynine is a minor alkaloid but may have a significant contribution to the pharmacologic effects of kratom extract. Compared with mitragynine, speciocilatine has a 3-fold higher binding affinity at MOR [43]. Additionally, some kratom products may be adulterated with speciocilatine at concentrations greater than would be expected from naturally-derived kratom.
Pharmacokinetics
●Absorption – Following oral administration, kratom alkaloids are rapidly absorbed and achieve peak concentrations within one hour. In a study of nine volunteers drinking kratom tea, peak serum concentrations were reached in an average of 50 minutes [20,44].
●Distribution – Kratom demonstrates two compartment distribution with a volume of distribution of 38 L/kg [44].
●Metabolism – Kratom alkaloids predominantly undergo hepatic metabolism involving multiple cytochrome oxidase isoenzymes, including CYP3A4, CYP2D6, and CYP2C9 [45]. 7-hydroxymitragynine is formed by dehydrogenation of mitragynine by CYP3A4. Mitragynine also undergoes hydrolysis and forms glucuronide and sulfate conjugates, which are ultimately excreted in the urine.
●Elimination – The half-lives of mitragynine and 7-hydroxymitragynine are approximately 3.5 and 2.5 hours, respectively [3]. The terminal half-life of mitragynine was 23 hours after oral ingestion [20,44]. Minimal amounts of mitragynine are excreted unchanged in urine. Steady state concentrations of mitragynine in blood are reached within eight to nine days; 7-hydroxymitragynine concentrations within seven days [20].
CLINICAL MANIFESTATIONS OF TOXICITY
Overview — Potential adverse effects associated with kratom use and/or product adulterants can broadly be divided into acute and chronic effects (although the full range of effects is unknown):
●Acute – A United States (US) poison center study identified the most frequent acute clinical effects described in self-reported single-substance kratom exposure [8]:
•Agitation/irritability – 23 percent
•Tachycardia – 21 percent
•Nausea – 15 percent
•Drowsiness/lethargy – 14 percent
•Vomiting – 13 percent
•Confusion – 11 percent
•Hypertension – 10 percent
•Seizures (single or multiple) – 10 percent
•Tremor – 7 percent
•Abdominal pain – 7 percent
•Dizziness – 5 percent
•Hallucinations – 5 percent
Other less common but serious acute clinical effects included respiratory depression (4 percent), apnea (0.5 percent), cyanosis (0.3 percent), coma (3 percent), bradycardia (1 percent), rhabdomyolysis (1 percent), acute kidney injury (0.5 percent), and cardiac arrest (0.4 percent). These effects may be due to kratom alkaloids, or coingested material. Acute clinical effects lasted less than eight hours for most (53 percent), but in some (14 percent) lasted more than 24 hours.
However, the clinical features of isolated kratom overdose have not been rigorously described. In general, published adverse events attributed to kratom have been derived from uncontrolled case reports or case series with inherent limitations in quality of data related to patient background; medical, social, or family history; scene findings; or analytical laboratory support.
Deaths associated with kratom use are uncommon and far outnumbered by deaths due to other opioid agonists [4]. Massive overdose may produce sedation and respiratory depression, which depends upon individual degree of tolerance to kratom. The precise mechanism of death from kratom use is unknown, but may be secondary to seizures or coingested opioids. Among 152 kratom-associated deaths, fentanyl was listed as the cause of death in most (65 percent) cases [46]. Over 80 percent of the patients in this cohort had a diagnosis of chronic pain. Even when medical examiners have listed kratom as the sole agent as cause of death, subsequent laboratory analyses have identified other psychoactive substances that could have contributed to death [47].
●Chronic – Chronic adverse effects include cholestatic liver injury and posterior leukoencephalopathy, both of which are reversible. Compulsive kratom use, dependence, and withdrawal are also recognized adverse event of longstanding kratom use.
Neurologic effects
●Seizures – There are multiple case reports of seizures following kratom use [48-50]. Kratom-associated seizures are idiopathic and idiosyncratic; the precise mechanism is undefined, and seizures are unique to a patient's characteristics and behaviors. Seizures, which often occur in the context of polysubstance use that includes kratom, may be more prevalent in patients with existing seizure disorders. Among patients without a known seizure disorder who convulsed after taking kratom, up to one-third were subsequently found to have an unrecognized seizure focus on electroencephalogram [51]. The patients in this study reported coingesting proconvulsant agents such as methamphetamine and diphenhydramine but could not be confirmed by the testing methods selected by the authors.
●Mental status changes – Kratom has been associated with various mental status changes, including agitation, irritability, lethargy, sedation, and coma. Patients with acute effects may be sedated but typically arouse with voice or tactile stimulation. Although the depth of sedation may reflect the severity of overdose, the dose of kratom needed to produce sedation, and the extent to which depressed mental status occurs in kratom-naïve as well as tolerant individuals, is unknown [48,49]
●Posterior reversible leukoencephalopathy – This has been rarely reported associated with kratom use [1,52].
Respiratory and cardiovascular effects — Kratom use has been associated with respiratory depression, bradypnea, cyanosis, and apnea [8,53,54]. These effects can be potentiated by, or may even be due to, concomitant use of opioids or other respiratory depressants. (See "Acute opioid intoxication in adults", section on 'Clinical features of overdose'.)
Reported cardiac effects of kratom include sinus tachycardia (most common), hypertension, and congestive heart failure [8,55]. One retrospective database study identified "disproportionate" reports of ventricular dysrhythmias, but this finding has not been replicated in cohorts of kratom users [38,56,57].
Hepatotoxicity — Kratom use is associated with reversible liver injury with a cholestatic pattern [58-63]. Symptoms start following several weeks of kratom use and can include nausea, fatigue, pruritus, dark urine, and even jaundice. Liver test abnormalities typically include serum aminotransferase of 100 to 400 U/L, alkaline phosphatase of 150 to 300 U/L, and bilirubin of 2 to 6 mg/dL.
Psychiatric, dependence, withdrawal — Frequent and prolonged ingestion of kratom has been associated with development of anorexia, weight loss, insomnia, depression, hallucinations, psychosis, dependence, and a use disorder. Greater than 50 percent of individuals who use kratom regularly for longer than six months develop severe dependence [64]. Signs and symptoms are similar to but less severe than those of opioid withdrawal (table 1) [50]. Rhinorrhea, irritability, and myalgias emerge 12 to 24 hours after cessation and can persist for up to seven days. In a study of 357 adults who use kratom three or more times per week for more than four weeks, at least one-half of patients reported experiencing withdrawal symptoms, which increased with frequency of use [17]. In patients with the most frequent use, approximately 40 percent reported at least one unsuccessful attempt to reduce or stop use.
Case reports describe neonatal abstinence syndrome following regular maternal kratom use during pregnancy [65,66]. (See "Neonatal abstinence syndrome (NAS): Clinical features and diagnosis".)
Others — The following have been associated with kratom use:
●Facial/photodistributed hyperpigmentation (long-term kratom use) [19,67,68]
●Hypothyroidism [1,69]
DIAGNOSTIC EVALUATION
History — In a patient who presents with concern for kratom adverse effects, we inquire regarding intent behind use (eg, self-harm, management of chronic pain, self-treatment of opioid withdrawal), route of administration, and relevant past medical history (eg, seizure disorder, substance use disorder, or substance use). Kratom intoxication is most common in patients with polysubstance use or a history of chronic pain managed with opioids, longstanding opioid use, or opioid use disorder.
In any suspected ingestion when the patient cannot provide a history, an exploration of alternative sources of information is warranted, including but not exclusive to emergency medical services, family members, invoices (such as from kratom vendors), pill bottles, medical records, and pharmacy information. (See "General approach to drug poisoning in adults", section on 'History'.)
In a patient with concern for self-harm attempt, the standard history includes reasons to suspect overdose (eg, suicide note, witnessed, reported to bystanders), time of ingestion or last dose, suspected coingestants, names of other accessible medications, the time from when the patient was last known well, and prior history of self-harm attempts. (See "Suicidal ideation and behavior in adults", section on 'Patient evaluation' and "Suicidal ideation and behavior in children and adolescents: Evaluation and disposition", section on 'Emergency evaluation of suicidal behavior'.)
Diagnosis — The diagnosis of adverse effects from kratom is based upon history and clinical findings and is established after excluding other potential intoxications. A threshold for acute or chronic effects from kratom has not been identified. Kratom adverse effects should be considered in a patient who reports using kratom and presents with findings associated with kratom (eg, agitation, seizure, opioid-like withdrawal following cessation, hepatoxicity).
In a patient who denies using kratom or who cannot provide a history, identifying kratom adverse effects are diagnoses of exclusion. Nontoxicologic and other toxicologic etiologies must be ruled out, recognizing that a diagnostic evaluation should never delay critical interventions and definitive care.
Ancillary studies — Laboratory and diagnostic testing depend upon signs, symptoms, and clinical findings.
In a patient with clinical features of opioid intoxication, agitation, poisoning, self-harm attempt, or altered mental status, including when kratom exposure is suspected, the goal of ancillary studies are to exclude other diagnoses and typically include the following (see "General approach to drug poisoning in adults", section on 'Toxicology screens (drug testing)'):
●Capillary blood glucose measurement ("fingerstick glucose") to exclude hypoglycemia as the cause of altered mental status
●Serum acetaminophen, salicylate, and ethanol concentrations to exclude these common coingestions
●Serum chemistries, liver enzymes, creatine kinase, and complete blood count
●Electrocardiogram (ECG) to screen for poisoning by drugs that affect the QRS or QTc intervals
●Pregnancy test in people of childbearing potential
●Computed tomography of the brain in a patient with unexplained altered mental status or focal neurologic abnormalities
Commonly available qualitative urine drug screens used in emergency departments, hospitals, and substance use treatment programs do not detect either mitragynine or 7-hydroxymitragynine [70,71]. (See "Urine drug testing".)
Role of mitragynine serum concentration — We do not routinely obtain mitragynine and 7-hydroxymitragynine serum concentrations since these assays are not available in most hospital laboratories and require sending to outside laboratories. Because of the prolonged time to obtain results, knowing alkaloidal concentrations does not typically alter management of a symptomatic patient. If necessary for confirmatory or forensic purposes, mitragynine and 7-hydroxymitragynine concentrations in urine and serum can be obtained from reference laboratories.
DIFFERENTIAL DIAGNOSIS —
High rates of polysubstance use, coupled with the risk of adulteration of kratom products, makes the evaluation for effects of other drugs important [3]:
●Opioids – Concurrent ingestion of opioids may confound the clinical presentation and evaluation of kratom exposure. If confirmatory testing is needed, fentanyl, oxycodone, and morphine, which are often coingested, can be detected with urine fentanyl, oxycodone, and opiate assays, respectively. (See "Acute opioid intoxication in adults".)
●Tramadol, O-desmethyltramadol – Seizures or signs of serotonin toxicity (eg, tremor, hyperreflexia, clonus) (table 2) can occur from these agents (sometimes labeled as "Krypton Kratom"). (See "Serotonin syndrome (serotonin toxicity)".)
●Benzodiazepines – An isolated benzodiazepine overdose typically produces central nervous system depression without respiratory depression. Coingestion of a benzodiazepine with kratom could culminate in respiratory depression, although the synergistic respiratory depressant effects observed with coadministration of opioids and benzodiazepines has not been observed with kratom. (See "Benzodiazepine poisoning".)
●Ethanol – Intoxication can be assessed by obtaining a serum concentration. (See "Ethanol intoxication in adults".)
●Diphenhydramine, jimsonweed (Datura stramonium), other anticholinergic agents – The presence of delirium with hyperactivity, mumbling speech, and dry skin suggests (table 2) poisoning with an anticholinergic agent. (See "Anticholinergic poisoning".)
●Caffeine – Recurrent seizures, severe tachycardia, ventricular extrasystoles, hypokalemia, and hyperglycemia suggests caffeine toxicity, which can be confirmed with an elevated serum caffeine concentration. (See "Acute caffeine poisoning".)
●Modafinil, phenylethylamine, propylhexedrine – Poisoning with these stimulants may be difficult to clinically distinguish from agitation/irritability due to kratom. In a case report, a patient who regularly used kratom that was adulterated with phenylethylamine developed an intracerebral hemorrhage [72]. (See "Acute amphetamine and synthetic cathinone ("bath salt") intoxication".)
Even in proven kratom exposures, other life-threatening toxicologic and nontoxicologic causes of injury must be considered in the differential diagnosis. Hypoglycemia must be excluded in every patient with altered mental status, even if kratom is suspected.
The differential diagnosis of adverse effects from kratom depends on the specific manifestations and is discussed in detail separately:
●Opioid toxicity (table 3) (see "Acute opioid intoxication in adults", section on 'Differential diagnosis')
●Sedation, confusion, coma (table 4) (see "Evaluation of abnormal behavior in the emergency department", section on 'Differential diagnosis')
●Opioid withdrawal (table 1) (see "Opioid withdrawal in adults in the emergency setting", section on 'Differential diagnosis')
●Seizures (table 5 and table 6 and table 7) (see "Evaluation and management of the first seizure in adults", section on 'Differential diagnosis')
●Liver injury with a cholestatic pattern (table 8) (see "Approach to the patient with abnormal liver tests", section on 'Elevated alkaline phosphatase')
MANAGEMENT
Supportive care — As with any poisoned patient, the initial treatment begins with rapidly assessing and addressing the patient's airway, breathing, and circulation. In a patient who presents with anything more than trivial symptoms, we suggest establishing intravenous (IV) access and continuous cardiac monitoring. End tidal carbon dioxide (EtCO2; ie, capnography) is useful for monitoring patients at risk for hypoventilation. Oxygen should be administered as needed. (See "Initial management of the critically ill adult with an unknown overdose", section on 'Systematic evaluation: The "ABCDE" approach'.)
In one published case of kratom-associated cardiac arrest, IV lipid emulsion (ILE) was associated with improvement in hemodynamic parameters prior to the patient's deterioration and death [73]. Administration of ILE for poisoning is discussed separately. (See "Calcium channel blocker poisoning", section on 'Lipid emulsion therapy'.)
No role for gastrointestinal decontamination — We do not routinely perform gastrointestinal decontamination with activated charcoal (AC) in patients with isolated kratom ingestion since mitragynine is rapidly absorbed following oral administration of kratom, seizures can lead to aspiration of charcoal, and intoxication often improves with supportive care alone. Administering AC provides no additional benefits but can increase the risk of aspiration and complicate airway management if the patient becomes more sedated. (See "Gastrointestinal decontamination of the poisoned patient", section on 'Activated charcoal'.)
Sedation or respiratory depression — We administer naloxone to any patient with sedation and respiratory depression. The dose and route of administration of naloxone for respiratory depression is the same as for opioid intoxication from other agents (table 9 and table 10). Case reports described improvements in mental status and respirations following naloxone administration (0.8 to 2 mg IV) to patients with bradypnea/apnea attributed solely from kratom [53,54]. Naloxone would be expected to improve toxicity from coingested opioids, if present. (See "Acute opioid intoxication in adults", section on 'Basic measures and antidotal therapy' and "Opioid intoxication in children and adolescents", section on 'Naloxone'.)
We do not administer flumazenil to a patient with suspected kratom use. Flumazenil is a nonspecific competitive benzodiazepine receptor antagonist. It would not be expected to improve kratom intoxication and may provoke seizures if the patient has a benzodiazepine coingestion. Its use in the somnolent patient with benzodiazepine poisoning is discussed elsewhere. (See "Benzodiazepine poisoning", section on 'Role of antidote (flumazenil)'.)
Seizures or agitation — In a patient with a prolonged seizure (>5 minutes) or recurrent seizures, first-line therapy is a benzodiazepine (eg, adults: midazolam 0.2 mg/kg IV/intramuscularly [IM], maximum dose 10 mg; lorazepam 2 to 4 mg IV; children: 0.1 mg/kg IV, maximum dose 4 mg). If additional medications are needed, phenobarbital or propofol, given their greater efficacy for toxin-induced seizures, is preferred over levetiracetam or phenytoin as second-line therapy. (See "Initial management of the critically ill adult with an unknown overdose", section on '"D": Disability and neurological stabilization' and "Convulsive status epilepticus in adults: Management", section on 'In-hospital treatment' and "Management of convulsive status epilepticus in children", section on 'In-hospital treatment'.)
In a patient with agitation that requires pharmacologic sedation, we prefer benzodiazepines (eg, lorazepam 2 to 4 mg IV/IM). A patient who is not adequately sedated following benzodiazepine administration may require tracheal intubation to facilitate escalation of pharmacologic sedation (eg, propofol, phenobarbital, dexmedetomidine). (See "Sedative-analgesia in ventilated adults: Management strategies, agent selection, monitoring, and withdrawal", section on 'Initiating sedative-analgesics'.)
Hepatotoxicity — Treatment of hepatoxicity is cessation of kratom use. Symptoms and biochemical liver tests improve one to two weeks after stopping kratom. Recurrent hepatotoxicity can occur with rechallenge [59,62].
Withdrawal syndrome/use disorder — In a patient with kratom dependence and withdrawal, we suggest buprenorphine for treating initial symptoms and for the long-term maintenance management. Induction and maintenance doses are typically less than those needed for opioid use disorder. In one case series, the maintenance buprenorphine dose was 4 to 8 mg, but 16 mg was needed in patients with heavier kratom use [74]. Trials supporting specific pharmacologic treatments for kratom withdrawal and dependence do not exist; evidence for buprenorphine is based on case reports and series [74-77]. (See "Opioid use disorder: Pharmacologic management", section on 'Buprenorphine: Opioid partial agonist'.)
In a patient with a normal or elevated blood pressure who declines buprenorphine or medications for opioid use disorder, a reasonable alternative or as an adjunctive agent for initial symptoms is clonidine. Mitragynine binds to alpha-2 receptors similar to clonidine. Dosing is similar to treatment of opioid withdrawal from other agents: clonidine 0.1 to 0.3 mg orally every hour until symptoms resolve (maximum total daily dose of 0.8 mg) while monitoring heart rate and blood pressure [78,79]. (See "Opioid withdrawal in adults in the emergency setting", section on 'Non-opioid adjunctive medications' and "Opioid withdrawal: Medically supervised withdrawal during treatment for opioid use disorder", section on 'Alpha-2 adrenergic agonists'.)
DISPOSITION —
Patients who have significant respiratory depression that does not resolve with naloxone (eg, require mechanical ventilation), have cardiovascular instability, or have been exposed to a hazardous coingestant should be admitted to a critical care setting.
Most patients with kratom adverse health effects can be safely managed as an outpatient or discharged from the emergency department following an observation period of four to six hours, provided that any concerning symptoms, such as central nervous system depression, have resolved. The patient should be able to ambulate safely and without assistance prior to discharge. We admit patients with persistent signs of intoxication beyond six hours to a monitored setting until symptoms resolve.
We admit a patient with kratom use who suffers a seizure for 24 hours to observe for additional seizures and to evaluate for other potential triggers of seizure activity, regardless of whether they have an existing seizure disorder. (See "Evaluation and management of the first seizure in adults" and "Seizures and epilepsy in children: Classification, etiology, and clinical features".)
A patient with a suspected self-harm attempt should be referred for urgent behavioral health evaluation. A patient with kratom dependence, withdrawal, or use disorder should be referred for substance use disorder treatment and given naloxone upon discharge.
ADDITIONAL RESOURCES
Regional poison centers — Regional poison centers in the United States are available at all times for consultation on patients with known or suspected poisoning, and who may be critically ill, require admission, or have clinical pictures that are unclear (1-800-222-1222). In addition, some hospitals have medical toxicologists available for bedside consultation. Whenever available, these are invaluable resources to help in the diagnosis and management of ingestions or overdoses. Contact information for poison centers around the world is provided separately. (See "Society guideline links: Regional poison centers".)
Society guideline links — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: General measures for acute poisoning treatment" and "Society guideline links: Treatment of acute poisoning caused by recreational drug or alcohol use" and "Society guideline links: Opioid use disorder and withdrawal".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Opioid use disorder (The Basics)" and "Patient education: Substance use disorder (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Pharmacology – Kratom (Mitragyna speciosa) is a natural product derived from a tree native to Southeast Asia, where it has been used for centuries for its stimulant, analgesic, and antidepressant properties. Kratom has also been used for self-treatment of opioid withdrawal. Kratom has stimulant effects at low doses; higher doses produce heightened alertness coupled with analgesia (or control of opioid withdrawal symptoms). Mitragynine is the most prevalent alkaloids and is primarily a weak agonist at the mu-opioid receptor. Commercially sold kratom products likely have alkaloidal concentrations that are different compared with natural leaf products, as well as potential adulterants. (See 'Regulation of kratom' above and 'Pharmacology' above.)
●Clinical manifestations – Kratom can produce acute as well as chronic effects. The full range of adverse effects associated with kratom use is unknown. Commonly reported adverse effects include agitation/irritability, tachycardia, drowsiness/lethargy, nausea/vomiting, abdominal pain, tremor, and confusion/hallucinations. Massive overdose may potentially produce sedation and respiratory depression but features of isolated kratom overdose have not been rigorously described. Less common but serious associated effects include seizures, bradycardia, rhabdomyolysis, acute kidney injury, and cardiac arrest. (See 'Clinical manifestations of toxicity' above.)
Frequent and prolonged ingestion of kratom has been associated with development of anorexia, weight loss, insomnia, depression, hallucinations, psychosis, dependence, and a use disorder. Signs and symptoms similar to opioid withdrawal (table 1) emerge 12 to 24 hours after cessation and can persist for up to seven days. (See 'Psychiatric, dependence, withdrawal' above.)
Kratom use has been associated with reversible cholestatic liver injury. (See 'Hepatotoxicity' above.)
●Diagnosis – The diagnosis of adverse effects from kratom is based upon history and clinical findings (eg, agitation, seizure, opioid-like withdrawal following cessation, hepatoxicity) and is established after excluding other potential intoxications. Adverse effects are most common in patients with polysubstance use or a history of chronic pain, longstanding opioid use, or opioid use disorder. (See 'Diagnostic evaluation' above.)
Commonly available qualitative urine drug screens do not detect either mitragynine or 7-hydroxymitragynine; we do not routinely obtain these serum concentrations since assays are not available in most hospital laboratories and do not typically alter management. (See 'Ancillary studies' above.)
●Differential diagnosis – Since rates of polysubstance use are very high and kratom products can contain adulterants, it is important to evaluate for effects of drugs such as opioids (fentanyl, morphine), tramadol, anticholinergic agents (diphenhydramine, jimsonweed), sedative-hypnotics (benzodiazepines, ethanol), caffeine, and stimulants (modafinil, phenylethylamine, propylhexedrine). (See 'Differential diagnosis' above.)
●Management of acute effects – Acute effects associated with kratom are managed primarily with supportive care. (See 'Supportive care' above.)
In a patient with sedation and respiratory depression with concern for kratom exposure, we administer naloxone similar to opioid intoxication from other agents (table 9 and table 10). (See 'Sedation or respiratory depression' above.)
In a patient with a prolonged seizure (>5 minutes), recurrent seizures, or agitation, first-line therapy is benzodiazepines (eg, adults: lorazepam 4 mg intravenous [IV]; children: 0.1 mg/kg IV, maximum dose 4 mg). For a patient with kratom use who suffers a seizure, we admit for 24 hours to observe for additional seizures and to evaluate for other potential triggers of seizure activity. (See 'Seizures or agitation' above and 'Disposition' above.)
●Management of kratom withdrawal or use disorder – In a patient with kratom dependence and withdrawal, we suggest buprenorphine for treating initial symptoms and for the long-term maintenance management (Grade 2C). Induction and maintenance doses are typically less than those needed for opioid use disorder. The evidence is based on case series. (See 'Withdrawal syndrome/use disorder' above.)
In a patient with a normal or elevated blood pressure who declines buprenorphine or medications for opioid use disorder, a reasonable alternative or as an adjunctive agent for initial symptoms is clonidine. Dosing is similar to treatment of opioid withdrawal from other agents: clonidine 0.1 to 0.3 mg orally every hour until symptoms resolve (maximum total daily dose of 0.8 mg) while monitoring heart rate and blood pressure.
