Increases in Kratom-Related Reports to Poison Centers — National Poison Data System, United States, 2015–2025

MMWR Morbidity and Mortality Weekly Report · 2026-03-26 · 2 citations

Kratom, the leaves of a tropical evergreen tree (Mitragyna speciosa), is traditionally consumed in Southeast Asia for pain relief, mood enhancement, and to relieve symptoms of opioid withdrawal. Kratom contains psychoactive compounds that interact with opioid receptors and is widely available in various forms in the United States. Its evolution from natural leaf to high-potency alkaloid products has raised concerns about toxicity. Data on kratom-related use that resulted in a report to the National Poison Data System (NPDS) (i.e., kratom exposure report) during 2015-2025 were analyzed to assess trends by exposure report type, demographic characteristics of persons exposed, and outcomes. During the past 11 years, poison centers received a total of 14,449 kratom exposure reports; the record high 3,434 reports in 2025 represent an increase of approximately 1,200% compared with the 258 reports in 2015. Most reports involved males and young adults aged 20-39 years, but reports among adults aged 40-59 years increased most sharply, with rates nearly overlapping with those among young adults by 2025. Although single-substance exposure reports accounted for most reports (62%), multiple-substance reports occurred at higher rates (range = 467-5,442 per 1 million multiple-substance drug exposure reports versus 388-4,045 per 1 million single-substance drug exposure reports), were associated with more hospitalizations (44%-56% versus 24%-29% annually) and serious (life threatening, pronounced, prolonged, or systemic) outcomes (57%-66% versus 41%-49% annually), and accounted for the vast majority of kratom-associated deaths during the study period (184 of 233; 79%). NPDS data indicate that kratom-related reports to poison centers are increasing and expanding among demographic groups, underscoring the value of ongoing surveillance to identify high-risk patterns of kratom use and guide strategies to reduce risks from multiple-substance exposure reports.

Increase in Poison Center Reports Linked to Kratom-Containing Kava Products — National Poison Data System, United States, 2000–2025

MMWR Morbidity and Mortality Weekly Report · 2026-04-02

Kava (Piper methysticum), a central nervous system depressant derived from a plant in the pepper family native to the Pacific Islands, is traditionally consumed in religious, cultural, political, and social ceremonies. In the United States, kava emerged in the late 1990s and has experienced renewed growth and product diversification since the 2010s, with increasing availability of concentrated extracts and ready-to-drink beverages. These commercial products are commonly marketed as healthy alternatives to alcohol, sold near college campuses, and increasingly being combined with kratom, a psychoactive botanical with opioid-like effects, raising safety concerns. Data on kava-related use during January 2000-December 2025 that resulted in a report to the National Poison Data System (i.e., kava exposure report) were analyzed to assess trends by users' demographic characteristics, exposure type, and outcomes. Kava-related exposure reports declined sharply after a 2002 Food and Drug Administration advisory on kava-associated severe liver injury but have risen steadily since 2011, reaching 203 reported exposures in 2025. Reports primarily involved adults aged ≥20 years, but demographic characteristics have changed over time. During 2000-2001, reports primarily involved females and included more children aged ≤12 years, whereas exposure reports since 2013 have predominantly involved men; reports involving children have been rare. Since 2017, reports involving combined use of kava and kratom have increased, reaching 30% (61) of all kava reports in 2025. These increases have coincided with higher rates of serious reported clinical outcomes in recent years (32% in 2025 compared with 12% in 2000). These data indicate a resurgence of overall kava exposure reports to poison centers, as well as an increase in kratom-related kava reports, which has coincided with higher rates of serious clinical outcomes. The findings in this report suggest the need for enhanced surveillance for, clinical awareness of, and public education regarding commercial products containing kava.

Comment on: We need a standardized North American acetylcysteine dosing regimen for the treatment of paracetamol (acetaminophen) poisoning

Clinical Toxicology · 2026-04-17

14 Surveillance of a Top Trending Designer Benzodiazepine at an Academic Medical System

American Journal of Clinical Pathology · 2025-11-01

Abstract As the field of novel psychoactive substances (NPS) has expanded, designer benzodiazepines (DBZDs) have become a significant drug class. One of the challenges in detecting NPS drugs is that the chemical structure is constantly modified, likely in an attempt to avoid legal sanctions. Historically, there have been multiple different compounds circulating within the drug class DBZDs, making it difficult for clinical laboratories to develop assays for detection. Since the end of 2022, a single drug known as bromazolam has emerged as the primary DBZD being detected. In this work, we investigated the cross-reactivity of bromazolam in the urine benzodiazepine screen and to evaluate clinical patient urines submitted for urine drug testing for the presence of bromazolam. Initial evaluation of bromazolam included determining cross-reactivity of the drug in urine benzodiazepine screens. Two immunoassays were evaluated, the Abbott Alinity c Benzodiazepines screen and the Emit II Plus Benzodiazepine assay, by spiking drug screen negative urine with bromazolam. The lowest concentration of bromazolam that screened positive for both assays was 200 ng/mL. To evaluate the clinical prevalence of the drug, patient urines were evaluated during the time frame of October to December 2024. Samples were selected for bromazolam confirmation testing if the urine screened positive in one of the following urine drug screens: benzodiazepines, fentanyl, cocaine, amphetamines or PCP. A qualitative confirmation method was developed using liquid chromatography tandem mass spectrometry (LC-MSMS) with multiple reaction monitoring to identify the presence of bromazolam. The evaluation of patient urine identified bromazolam in 36 urine samples over a time period of 3 months. Of these 36 samples, 20 (56%) screened positive by the benzodiazepine drug screen and of these, 4 urines were co-positive with other benzodiazepines. Other drugs detected in the urine samples were also evaluated, and the highest co-positivity was observed with fentanyl (86%), followed by cocaine (75%) and methamphetamine/amphetamine (47%). Additionally, 33 patients had at least two co-positive drug classes, and notably, bromazolam was never detected in isolation. While the urine benzodiazepine screen was able to detect bromazolam during a spiking study, evaluation of clinical patient urines showed that an LC-MSMS approach was more sensitive for detecting bromazolam. Preliminary testing showed that bromazolam is often present with other drugs typically included in a urine drug screen.

A phase 1, first-in-human, open label, single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of stabilized isoamyl nitrite nasal spray in healthy adult participants

Journal of Pharmacology and Experimental Therapeutics · 2025-04-17

Stabilized isoamyl nitrite (SIAN) is a novel small molecule, therapeutic candidate for the treatment of cyanide poisoning. SIAN improves survival and has a demonstrated pharmacodynamic (PD) effect in cyanide challenged nonhuman primates. Here, we report results of phase 1, first-in-human study evaluating the safety, tolerability, pharmacokinetic (PK), and PD of SIAN nasal spray in healthy human subjects (NCT05194358). SIAN was intranasally administered in ascending doses at 2 sites in Texas and Tennessee in the United States. A total of 47 subjects were enrolled across 7 dose cohorts evaluating single doses from 20 to 300 μL. Following the dosing of sentinels in each cohort, safety, PK, and PD data were interpreted by a Safety Monitoring Committee to permit dosing of additional subjects in the cohort or escalation to the next dose level. Isoamyl alcohol peak plasma concentrations were reached within 2 minutes and were highest after a 250 μL dose (125 μL/nostril). This trend was also observed for PD parameters, including a metHB peak at 2 minutes with associated increase in heart rate and systolic and diastolic blood pressure. SIAN was generally well tolerated, no serious or severe drug-related effects were observed, and there were no clinically significant changes in vitals or laboratory parameters. We conclude that SIAN, a potential new treatment for cyanide poisoning, was safe, well tolerated, and showed a relationship between PK and PD parameters at the doses tested. SIGNIFICANCE STATEMENT: This is the first-in-human clinical study to evaluate intranasal stabilized isoamyl nitrite, which was shown to be safe, well tolerated, and to elicit a measurable pharmacokinetic and pharmacodynamic response in healthy human subjects at the doses tested. This study paves the way for investigating stabilized isoamyl nitrite further as a potential emergency treatment for cyanide poisoning.

Once, twice, three times a bite victim: recidivism in snake envenomation

Clinical Toxicology · 2025-07-07 · 1 citations

INTRODUCTION: We believe there are certain behaviors that may predispose people to being bitten by a snake. The purpose of this study was to describe cases reported to the North American Snakebite Registry in which the snakebite victim acknowledged multiple lifetime snakebites and to test the hypothesis that male sex, intentional handling of the snake, alcohol consumption, and maintaining snakes in captivity are associated with sustaining multiple snakebites in a lifetime. METHODS: This was a retrospective review of de-identified patient information reported to the snakebite registry between January 1, 2013 and December 31, 2023. Data regarding the circumstances of the snake encounter, patient demographics, previous snakebites, antivenom administration, and clinical outcomes were reviewed. RESULTS: Of the 2,140 snakebites reported during the study period, 94 (4.4%) involved patients with a history of one or more previous snakebites. Males accounted for 80 (85.1%) victims. Sixty-one (64.9%) bites followed intentional interaction with the snake. Alcohol use was reported in 15 (24.6%) of these cases. Captive snakes were responsible for 18 (29.5%) bites. Of the bites that resulted from unintentional snake interaction, alcohol was implicated in three (9.1%) cases. One (3%) bite was from a captive snake. Acute hypersensitivity reactions were observed in six (7.5%) patients who received antivenom. DISCUSSION: Most patients with multiple lifetime snakebites were intentionally interacting with the snake just prior to being bitten. Maintaining snakes in captivity was reported more frequently in patients with previous bites than among the general snakebite population. Although alcohol use was more common among patients who intentionally interacted with snakes, most patients with multiple lifetime snakebites did not report preceding alcohol use. CONCLUSIONS: Male sex, intentionally handling snakes, and maintaining snakes in captivity are more common in patients with multiple lifetime snakebites than those who have experienced only one bite.

Seizures associated with single substance exposures in pediatric patients: a 15-year retrospective study

Clinical Toxicology · 2025-06-30

INTRODUCTION: This study aims to evaluate the trends, demographics, outcomes, and substances associated with single-substance exposures associated with in seizures in pediatric patients over 15 years. METHODS: was conducted from 2009 to 2023, including pediatric patients (<20 years) who experienced seizures as a clinical effect associated with single-substance exposures. Cases with single seizures, multi/discrete seizures, or status epilepticus were included. Trends in annual frequency, seizure rates (per 100,000 exposures), and substances associated with seizures were examined. RESULTS: Thirty thousand nine hundred and eighty-five patients with single-substance exposures associated with seizures were identified, including 1,712 cases of status epilepticus. Reports to poison centers saw an increase in cases with seizures from 1,418 in 2009 to 2,749 in 2023. The seizure rate increased from 88 to 237 per 100,000 exposures. Patients aged 13-19 years accounted for the majority of cases (66.9%), followed by aged 0-5 years (24.0%) and 6-12 years (9.1%). Diphenhydramine and bupropion were the leading contributors, with diphenhydramine-related seizures increasing from 85 in 2009 to 404 in 2023 and bupropion cases rising from 162 in 2013 to 431 in 2023. Moderate and major effects were reported in 41.9% and 35.8% of cases, respectively, with nearly half (47.8%) requiring admission to critical care units. DISCUSSION: The current study shows an increase in substance-related pediatric seizures, particularly among adolescents and females. The significant need for critical care in nearly half of these cases shows the severity and potential long-term impact of these exposures. CONCLUSIONS: Pediatric seizures associated with single-substance exposures are on the rise, driven primarily by diphenhydramine and bupropion. This trend highlights the need for targeted prevention strategies to reduce the burden of toxic exposures and safeguard the well-being of pediatric populations.

Detection of bromazolam alongside other misused substances

Clinical Toxicology · 2025-11-11

INTRODUCTION: Epidemiological and toxicological data available on patients exposed to bromazolam are limited. We report a case series of 32 patients presenting with bromazolam-positive urines. METHODS: Between 1 October and 31 December 2024, 6,083 samples from 5,289 patients presenting to inpatient and outpatient services at four hospitals, were submitted for clinical urine drug screening. Samples were selected for bromazolam confirmation testing if they screened positive for benzodiazepines, fentanyl, cocaine, amfetamines or phencyclidine. A qualitative confirmation method was developed using liquid chromatography tandem mass spectrometry with multiple reaction monitoring. RESULTS: = 24; 69%). DISCUSSION: The bromazolam and fentanyl co-positivity suggests that bromazolam may be increasingly found in illicit fentanyl supplies, heightening the risk for respiratory depression and a lack of full response to naloxone. This pattern may also reflect a co-use pattern among opioid users. CONCLUSION: The study findings highlight the importance of early warning and toxico-surveillance programs powered with advanced analytical confirmation capabilities for timely detection of emerging new psychoactive substances.

A toxicologist’s guide to poison ivy’s itch and bee stings’ burning pain – 2 examples of nature’s chemical warfare

2025-08-07

Psilocybin Exposures Reported to U.S. Poison Centers: National Trends Over a Decade

Journal of Adolescent Health · 2024 · 18 citations

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