Abstract
Kratom (Mitragyna speciosa) is an increasingly available psychoactive plant product marketed for pain relief, energy enhancement, and wellness benefits despite lacking FDA approval for medical use. This article reviews the epidemiology, pharmacology, toxicology, clinical presentation, and treatment considerations associated with kratom exposure. Evidence from poison center surveillance and healthcare utilization data demonstrates rising rates of emergency department visits, hospitalizations, and fatalities, frequently involving polysubstance use. The principal alkaloids, mitragynine and 7-hydroxymitragynine, exert opioid-like effects while also interacting with adrenergic, serotonergic, and dopaminergic pathways, producing a complex and variable toxidrome. Clinical manifestations range from mild stimulant effects to opioid-like sedation, respiratory depression, dependence, withdrawal, seizures, and hepatotoxicity. Diagnosis is challenging because routine drug screens do not detect kratom and definitive identification requires specialized laboratory testing. Current treatment remains largely supportive, with naloxone providing inconsistent benefit in severe toxicity. Given increasing morbidity and mortality, widespread retail availability, and the absence of accepted medical use, kratom presents a growing public health and emergency medicine concern.
Introduction
All over the world, for millennia humans and animals have experimented with substances that today we consider “drugs” and in emergency medicine falls into the general category of toxicology. The intentional and accidental consumption of psychoactive natural compounds spans our evolutionary biology, ethnobotany, and historical medicine.
Across the United States and around the world a pandemic is quietly playing out in emergency departments, physician offices and EMS. Its neither the coronavirus, nor fentanyl, but something more insidious and more readily available. The pandemic in discussion, is that of mitragyna speciosa, a tropical evergreen tree native to Southeast Asia, particularly Thailand, Malayasia, Indonesia and Papua New Guinea. In gas stations, supplement stores and convenience marts it is known as Kratom.
Commonly marketed, and used for energy and pain relief, the primary active alkaloids in the leaves are mitragynine and 7-hydroxymitgragynine. In low doses of 1-6G it acts as a mild stimulant – increasing alertness, physical energy and sociability. In moderate to high doses of 5-15G produces opioid-like effects, including analgesia, sedation and relaxation. It is not approved by the FDA for medical use, and the FDA has issued warnings regarding contamination and abuse risk.
Mortality and Morbidity
Over the last decade emergency department visits, hospitalizations and deaths have risen sharply driven by growing use, higher potency products, and frequent polysubstance co-exposure. The most current data originates in the poison center surveillance and in health system records as there is otherwise no national database. In 2015, the NPDS (National Poison Data System) reported 258 events, by 2025 the exposure incidents had risen to 3,434, The most significant age cohort is not what you think – data shows the incident rate highest among those aged 40-59.
Across the cohort, roughly 13% of all exposures result in severe medical outcomes (major effect or death). In the data set 31.8% of exposures lead to an admission, and 51.9% to a serious medical outcome. Mortality continues to rise at a rate of 1.6% per exposure, of which an overwhelming 79% are associated with multiple substances.
Victim Profile
Krystal Talavera, a 39-year-old mother of four and nurse from Boynton Beach, Florida, collapsed in her living room in June 2021 after consuming a concentrated kratom powder labeled "Space Dust". The Palm Beach County Coroner determined her cause of death was acute mitragynine intoxication, which resulted in fatal respiratory failure. Her family filed a wrongful death lawsuit arguing that the seller failed to disclose the hazards and addictive properties of concentrated kratom. In July 2023, a federal judge awarded her family more than $11 million in damages against the distributor.
Ethan Pope, a 23-year-old college graduate, died in December 2021 in his Cobb County apartment after using an over-the-counter liquid kratom extract. An autopsy conducted by the Georgia Bureau of Investigation concluded that Pope died from mitragynine intoxication, with no illicit drugs or alcohol found in his system. His parents subsequently filed a wrongful death lawsuit in 2022 against manufacturers, distributors, and advocacy entities, alleging that the liquid extracts delivered dangerously high alkaloid concentrations without adequate safety warnings.
These cases provided a foundation for kratom awareness, but neither resulted in scheduling or illegality. In late July 2026, police in West Melbourne, Florida, arrested a father on charges of manslaughter and child neglect following the fatal overdose of his 2-year-old daughter earlier in the year. Toxicology and investigative findings determined the child died from accidental acute kratom toxicity after accessing unsecured kratom products in the home. In July 2026, Dauphin County Coroner Graham Hetrick issued a public safety warning after confirming two deaths in the county linked directly to kratom toxicity. Hetrick highlighted the rapid proliferation of unregulated, high-potency extracts and synthetic formulations as primary drivers of these adverse fatal reactions
Biochemical Physiology
Mitragynine, the primary indole alkaloid isolated from Mitragyna speciosa, is a lipophilic, corynanthe-type monoterpene alkaloid. Following oral ingestion, mitragynine undergoes gastrointestinal absorption with an oral bioavailability constrained by extensive first-pass hepatic metabolism; peak plasma concentrations (Tmax ) are reached rapidly, typically between 0.8 and 1.8 hours in human subjects. Biologically, mitragynine and its active oxidative metabolite, 7-hydroxymitragynine, cross the blood-brain barrier to act as atypical partial agonists at μ-opioid receptors with G-protein pathway bias and negligible β-arrestin-2 recruitment, alongside competitive antagonism at κ- and δ-opioid receptors.
Kratom alkaloids share mechanistic, clinical and subjective similarities with several specific opioids including buprenorphine, oliceridine, and tramadol. But clinically and subjectively kratom mimics codeine and hydrocodone, morphine and oxycodone – especially when used in high doses. You should read this as “potent opioids are available without medical oversight or physician order directly from the local gas station.”
Additionally, mitragynine interacts with central α2 -adrenergic, serotonergic (5-HT2A ), and dopamine pathways, producing a dose-dependent pharmacological profile characterized by mild stimulation at lower concentrations and opioid-mediated analgesia and sedation at elevated systemic exposures.
Systemic clearance is mediated predominantly via hepatic phase I oxidative biotransformation. Mitragynine demonstrates a high apparent volume of distribution (Vd /F≈38 L/kg), indicating extensive peripheral tissue penetration and lipid sequestration. Pharmacokinetic profiling in humans conforms to an oral two-compartment model characterized by multiphasic elimination; while initial systemic redistribution is rapid, the terminal elimination half-life (t1/2 ) extends from approximately 23 to over 43 hours following single doses and up to 68 hours under steady-state conditions. Renal excretion of unchanged parent compound is negligible (<0.2%), with elimination occurring almost entirely as hepatic metabolites cleared through renal and biliary routes. Management of patients presenting with kratom ingestion or overdose are also likely to have other substances on board which may potentiate or be potentiated by the kratom.
Toxicology
Standard point-of-care urine drug screens (such as routine 5-, 10-, or 12-panel immunoassays) do not detect kratom alkaloids. Identification requires a specialized laboratory assay, with Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) and Gas Chromatography–Mass Spectrometry (GC-MS) serving as the gold standard for definitive identification and quantification in blood, serum, or urine. Specialized targeted immunoassays (ELISA) can serve as initial presumptive screens, but chromatographic confirmation is necessary to reliably distinguish mitragynine and 7-hydroxymitragynine from structurally similar plant diastereomers (such as speciociliatine and mitraciliatine) that naturally occur in Mitragyna speciosa.
Symptoms of Regular Use
Regular use can be difficult to detect while a user is ingesting lower dose, but as dose dependency and frequency dominate the patient will exhibit mild to moderate opioid use disorder. Chronic uses cause constipation, anorexia and weight loss, nausea, dry mouth, sleep disturbance, itching, sweating and intermittent erectile dysfunction. Long term high does use may result in hyperpigmentation, hair loss and fatigue. Possible, though less common, symptoms include elevated cholesterol, and hepatotoxicity. The most reliable identifier is withdrawal syndrome in abstinence. Such a patient will experience myalgias, muscle spasms, joint pain, insomnia, rhinorrhea, hot flashes, sweating, fever and itching. Although the physical manifestation is significant the psychological withdrawal symptoms are also challenging and include restlessness, irritability, anxiety, depression and perceptual disturbances.
Treatment
The foundation of acute kratom toxicity management is supportive care, with naloxone reserved for opioid-like respiratory or CNS depression. It is important to note, that naloxone response is variable and often incomplete because kratom’s toxidrome is only partially opioid (mu) mediated. There are no formal, society endorsed or specific pathways of care for acute kratom poisoning to reference. Instead, treatment protocols are built upon opioid overdose care, poison-center experience and small case series.
Conclusion
The evidence is overwhelming, and the law is clear. Under 21 U.S.C. § 812(b)(1), a Schedule I placement requires demonstrating a high potential for abuse, no currently accepted medical use in treatment in the United States, and a lack of accepted safety for use under medical supervision. The primary psychoactive alkaloids, mitragynine and 7-hydroxymitragyine act as partial and full agonists at the m-opioid receptors. 7-OH-MG exhibits higher potency at -opioid receptors than morphine, driving compulsive redosing, escalating tolerance, and physiological dependence. There is no accepted or approved medical use, and abrupt cessation in dependent individuals precipitates a classic opioid withdrawal syndrome.
By acting across adrenergic, serotonergic, dopaminergic and opioid pathways, kratom toxicity can present simultaneously with opioid sedation alongside sympathomimetic and serotonergic symptoms [severe agitation, hypertension, tachycardia, hyperthermia, and serotonin syndrome risk]. Kratom lowers the seizure threshold and can induce spontaneous or breakthrough seizures even in individuals without prior history. Repeated administration is associated with significant hepatotoxicity, including cholestatic liver injury and associated jaundice.
Commercial vendors market highly concentrated liquid shots, tablets and related products for rapid delivery and enhanced potency. The lack of development controls means that the stated ingredients and concentrations are likely inaccurate, contaminated, and adulterated. Federal scheduling under the CSA establishes uniform legal authority to remove this substance from over-the-counter retail, restrict importance, and mandated investigation. The time is now.