IAFTC Newsletter. Volume 1. Issue 1. November 19, 2025.
Jay M. Gehlhausen, Ph.D., DABFT-FD1
1Forensic Toxicologist and Expert Witness, JG Tox LLC, Apex, NC 27539
This is an open-access article under the CC BY-NC-ND license.
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Abstract
Kratom (Mitragyna speciosa) is a Southeast Asian botanical product that has gained increasing prominence in forensic toxicology casework throughout North America. The leaves of this tropical tree contain numerous indole alkaloids, most notably mitragynine and 7-hydroxymitragynine, which exhibit complex pharmacological activity at opioid and adrenergic receptors. At low doses, kratom produces stimulant effects, while higher doses result in sedation and euphoria similar to opioid intoxication. The legal status of kratom remains controversial; while it is classified by the U.S. Drug Enforcement Administration as a Drug and Chemical of Concern, federal scheduling efforts have stalled, leading to a patchwork of state-level regulations. Forensic laboratories have developed robust LC-MS/MS methods for detecting kratom alkaloids and their metabolites in biological specimens, though therapeutic and toxic concentration ranges remain poorly defined. Published case reports document mitragynine blood concentrations ranging from 10-970 ng/mL in driving under the influence investigations and 10-4,310 ng/mL in fatal cases, though polydrug use is common. With over 1,200 adverse events reported to the FDA between 2008 and 2024, including 637 fatalities, and increasing prevalence in impaired driving cases, forensic toxicologists require familiarity with kratom's chemistry, pharmacology, and analytical detection. This review synthesizes current knowledge regarding kratom's chemical composition, metabolism, toxicological effects, and legal status to assist toxicologists and legal professionals in evaluating kratom-related cases.
Introduction
Mitragyna speciosa, or kratom, is a tropical tree native to Southeast Asia used historically as a natural stimulant and analgesic. Local residents in the region also refer to the tree as thang, kakuam, ketum, or biak. Early purveyors of Mitragyna speciosa would chew or smoke the leaves as a respite from demanding physical labor. Cultural acceptance developed over time in Thailand and Malaysia, and kratom would later become a global commodity. The chemical composition is not fully characterized, but fifty-four known alkaloids have been identified, two of which, mitragynine and 7-hydroxymitragynine, exhibit significant neurological activity (DEA, 2024). Plant varieties differ in composition and potency based on regional soil and climatic conditions; Thai kratom, for example, is the most potent due to a more favorable climate. Another variety of kratom found in Malaysia, referred to as ketum, has a lower prevalence of the psychoactive drug, mitragynine.
In recent years, products manufactured with concentrated levels of mitragynine have been marketed as health and medicinal products. In the United States, for example, the plant leaves are sold as a powder available through internet sites and herbal shops. Newer formulations, such as brewed tea or concentrated drinks, are also prepared from the crushed leaves. Kratom is available from numerous vendors with names like Kona and Star (Kratom, 2025). Some of these products are highly potent, causing state governments to take notice following anecdotal reports of life-threatening intoxication and dependency.
The Legal Status of Kratom
Despite evidence of misuse and opiate-like pharmacology, the legal status of kratom remains in limbo. In September of 2016, the Drug Enforcement Administration (DEA) announced plans to classify mitragynine and 7-hydroxymitragynine as Schedule I narcotics using the administration’s emergency classification authority (Erickson, 2016). The pushback from Congress came immediately. With opposition coming from fifty-one members of the House of Representatives, the DEA was forced to reconsider the kratom ban. The Drug Enforcement Administration remains skeptical of the drug’s efficacy and considers kratom a Drug and Chemical of Concern (DEA, 2024). Advocates and several research centers, on the other hand, have pointed to evidence of relief from anxiety, management of opioid dependence, and limited abuse potential as justification for legal status. Even so, only limited legislative progress has been made at the federal level.
In the absence of federal regulation, fifteen states have addressed concerns from the legal and medical communities by passing their own laws. Alabama, Arkansas, Indiana, Rhode Island, Vermont, and Wisconsin have banned mitragynine and 7-hydroxymitragynine-containing products. Other states have attempted to limit abuse by enacting age requirements. Tennessee has restrictions on the synthetic products but maintains legal status for the plant material (CRS, 2023). Kratom laws vary significantly across the fifty states. Issues relating to impairment and Driving While Impaired (DWI) can only be managed on a case-by-case basis. The public debate over the efficacy of kratom will continue because few controlled studies have been performed to understand the acute and long-term effects of kratom on human health. The actual risk of psychological and physical addiction has not been elucidated through scientific study.
The Chemistry of Kratom
The psychoactive constituents of kratom are characterized as alkaloids. This broad class of naturally occurring organic compounds, including compounds like caffeine and nicotine, contains at least one nitrogen and exhibits weakly basic chemistry. Other alkaloids, such as theobromine and theophylline, derivatives of caffeine, are amphoteric. Alkaloids dissolve poorly in water but readily dissolve in organic solvents such as diethyl ether, an important consideration in the preparation of concentrated drinks. Alkaloids can also form salts that are freely soluble in water and ethanol. The alkaloids in kratom, for example, are classified as indole alkaloids, containing the structural moiety of indole, which is structurally related to the pentacyclic indole alkaloids, yohimbine and voacangine (Basiliere, 2020).
Indoleis an organic compound classified as an aromatic heterocycle with a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered pyrrole ring. Indoles are widely distributed in nature, most notably as the amino acid tryptophan and neurotransmitter serotonin. There are more than 4100 known indole alkaloids, which often exhibit significant physiological activity. The indole structure is the backbone of the kratom alkaloids. Mitragynine is the most abundant active ingredient. In one study, a mitragynine concentrate extracted from the tree leaves contained 66% and 12% by weight from Thai and Malaysian varieties, respectively (Karunakaran, 2022). The plant contains fifty additional alkaloids that are present at much lower concentrations and have not been fully investigated (Karunakaran, 2022).
Pharmacology of Mitragynine and 7-hydroxymitragynine
At low dose levels, mitragynine exhibits mild stimulant effects, but as the dosage increases, an individual can experience sedation and euphoria similar to opioid use; this duality relates to concurrent α-adrenergic and opioid receptor induction. Notably, mitragynine has a long half-life in blood, estimated at 23 hours, which increases the risk of drug toxicity during binge use (Trakulsrichai, 2015). Doses of 2 to 10 grams of leaf material are more typical of the casual user. Physiological effects begin within 5 to 10 minutes after ingestion and last for 2 to 5 hours. Pharmacological investigations demonstrate that mitragynine and 7-hydroxymitragynine have µ-opioid receptor agonist activity, but mixed Δ and κ opioid activity has also been observed.
The major kratom alkaloids mitragynine, paynantheine, speciogynine, and speciociliatine, in addition to several metabolites, have been detected in the urine of rats and humans following ingestion of kratom. There are a few studies describing the metabolic pathways of mitragynine, although recently there has been renewed interest in this area of research. An early study by Zarembo et al. reported that oxidation and hydroxylation were the primary metabolic routes. Mitragynine is known to undergo hepatic metabolism (Zarembo, 1974). Phillipp et al. conducted the first comprehensive in vivo study: rats were administered a single 40 mg/kg dose of mitragynine by gastric intubation (Philipp, 2009). The authors reported that phase I metabolism involved hydrolysis and demethylation, followed by oxidative and reductive transformations to produce carboxylic acid and alcohol derivatives. Additionally, mitragynine undergoes extensive phase II metabolism, producing both glucuronide and sulfate conjugates (Basiliere, 2020).
Kratom Toxicology
There is no in-depth understanding of kratom toxicology or how the drug influences the central nervous system (CNS). There have been recent human and animal studies involving kratom alkaloids, but at present, there are no authors who have proposed therapeutic and toxic concentration ranges (Maxwell, 2020). A review of the kratom literature has found blood concentrations between 10 - 970 ng/mL and 10 – 4310 ng/mL for DUID and death investigation cases, respectively (Society of Forensic Toxicologists, 2020). However, these wide ranges preclude the development of a practical safety scale. Similarly, there are no comprehensive studies on the interaction of mitragynine with other drugs despite postmortem case reports involving kratom, mixed drug fatalities (McIntyre, 2015).
Acute side effects observed during emergency room presentations include nausea, itching, sweating, dry mouth, constipation, and loss of appetite. More severe toxic effects, like psychosis and hallucinations, have also been reported. As kratom products have become readily available in North America, reports of adverse medical events and emergency room visits have also increased. The American Association of Poison Control Centers’ 2022 report indicates that kratom accounted for 1,278 case mentions, 794 single exposures, and 586 cases that involved treatment in a healthcare facility (Gummin, 2024). According to data from the Food and Drug Administration’s adverse event reporting system, mitragynine was identified in 1,255 cases from 2008 to 2024. Of these cases, 1,171 were classified as serious, and 637 reports involved fatalities (DEA, 2025).
The analysis of biological specimens for mitragynine and other kratom alkaloids has become routine since the development of robust LC-MSMS methods. The first reported analytical method for the quantitation of mitragynine was a high-performance liquid chromatography–ultraviolet detection (HPLC–UV) method measuring mitragynine in the serum of dosed rats, with a limit of quantitation (LOQ) of 100 ng/mL (Janchawee, 2007). More recently, a study by Le et al. reported a quantitative liquid chromatography–tandem mass spectrometry (LC–MSMS) procedure for the identification of mitragynine and other kratom alkaloids in human urine, including the metabolites 5-desmethylmitragynine and 17-desmethyldihydromitragynine (Le, 2012).
Conclusion
Kratom, with its wide array of commercial products, challenges a simple characterization as a drug-of-abuse or natural medicine. Kratom has vocal advocates and detractors. The active constituents, mitragynine and 7-hydroxymitragynine, have demonstrated complex pharmacology and myriad psychophysical effects. To date, there is no clear understanding of the toxicology, and claims of medical efficacy are unproven. Despite political support for legal status at the federal level, state governments have moved forward with regulations restricting the sale of kratom. Scientific research on kratom predominantly supports the Drug Enforcement Administration’s classification of kratom as a Drug and Chemical of Concern. The intent of this article was to inform toxicologists and attorneys about the properties of kratom since it is highly likely that cases of overdose and motor vehicle accidents will increase in the coming years.
Declaration of competing interest
The author serves as an expert witness in forensic toxicology cases and receives compensation for testimony and consultation services.
AI Disclaimer
Artificial intelligence tools were used to assist in the preparation of this manuscript, including reviewing, editing, and formatting. All scientific content has been verified by the author, who takes full responsibility for the accuracy and integrity of the work.
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