Kratom (Mitragyna speciosa)

Background: Kratom (Mitragyna speciosa), a Southeast Asian plant, has gained global prominence for its pharmacological properties and widespread use, particularly among vulnerable adolescents and youth, raising concerns about its impact.Objective: We reviewed existing studies to provide a comprehensive understanding of kratom use among adolescents and college students.Methods: We conducted a systematic review of studies published up to October 2024, using PubMed, Scopus, Web of Science, and Google Scholar databases. Search terms included "Kratom" or "Mitragyna speciosa" combined with terms related to adolescents and college students.Results: Six eligible studies conducted in Malaysia, Thailand, and the United States were identified. Distinct regional differences in patterns of kratom use were observed, shaped by cultural traditions in Southeast Asia and commercialization in the United States. Kratom use was more prevalent among males across regions, with variations shaped by socioeconomic status, psychosocial influences and recreational use. Available studies were limited to college students and those enrolled in a drug treatment program (one study). Generally, kratom was commonly used to self-manage withdrawal symptoms from opioids (heroin) and methamphetamines. Polydrug use emerged as a consistent theme across all studies, underscoring the complexity of kratom consumption in this population.Conclusion: The rising prevalence of kratom use among adolescents and college students demands attention. While kratom may hold potential as a harm reduction tool, evidence on its safety, efficacy, and long-term outcomes remain limited, highlighting the importance of distinguishing traditional practices from emerging recreational trends. This review points the need for targeted interventions, education, and regulatory frameworks.

STATEMENT OF PURPOSE INNOVATION OR HYPOTHESIS: Kratom, derived from the leaves of the plant Mitragyna speciosa, is an herbal supplement that has been used medically and recreationally for centuries, but has recently gained popularity in the United States for its analgesic and euphoric effects. The United States Food and Drug Administration (US FDA) has issued warnings against the use kratom due to potential health effects, including seizures. Seizures are one of the most commonly reported side effects associated with kratom use. The purpose of this paper is to determine whether there is a causal relationship between kratom use and seizures. DESCRIPTION OF METHODS AND MATERIALS: A systematic literature search was conducted to identify reviewed articles that contained information or data on kratom users experiencing seizures. Additionally, we mined adverse event data submitted to the Centers for Food Safety and Applied Nutrition's Adverse Event Reporting System (CAERS) database and the US FDA Adverse Event Reporting System (FAERS). These databases were selected to examine consumer-reported and healthcare-reported adverse event, providing a comprehensive list of seizure-related incidents potentially associated with kratom use. DATA AND RESULTS: Our search yielded a total of 42 articles, but only 11 met the selection criteria for inclusion. The 11 peer-reviewed articles included for analysis consisted of case reports (n = 6), case series (n = 2), retrospective observational (n = 2), and a paper discussing a summary of adverse events reported to the FAERS database. Across the 11 publications used in our analysis, we noted a total of 20 patients who reportedly experienced seizures after using kratom. However, only one patient was quantitatively positive for Mitragynine in their urine sample, so there was minimal proof of kratom use. There was no indication that the other 19 patients had their urine subjected to mitragynine screening which would have confirmed their use of kratom and internal metabolism after intake. Furthermore, the FAERS dashboard, only 22 of 481 kratom-related reports involved seizure (4.5%); the CAERS database had 18 reported seizures amongst 221,1

BACKGROUND: Mitragyna speciosa Korth. [Rubiaceae] is a tropical plant with opioid-like properties used for its metabolic altering effects, but data on the metabolic effects are lacking. This systematic review and meta-analysis aim to examine the effects of kratom use on parameters related to metabolic syndrome (MetS) in humans. METHODS: PubMed, Web of Science, Embase, and Cochrane Library databases were searched from inception to 6 September 2024 to identify eligible analytical studies examining the association between kratom consumption and metabolic effects. The effect estimates were summarized as mean differences (MDs) with 95% confidence intervals (CIs) and pooled using random-effects models. RESULTS: Five cross-sectional studies were included. The meta-analysis involving 1,458 adults observed significantly lower levels of serum low-density lipoprotein cholesterol (LDL-c) (MD -0.25-0.21 mmol/L; 95% CI: -0.39, -0.02), triglyceride (MD -0.17 mmol/L; 95% CI: -0.25, -0.09), while high-density lipoprotein cholesterol (HDL-c) levels increased (MD 0.07 mmol/L; 95% CI: 0.03, 0.11). Body mass index was also lower in adults using kratom when compared to the control group (MD -1.52 kg/m2; 95% CI: -2.81, -0.23). CONCLUSION: Kratom use in the adult population was associated with lower LDL-c, TG, BMI, and higher HDL-c levels. However, the total cholesterol and blood sugar lowering effects were not statistically significant. The findings suggest that kratom use may have a protective effect against certain metabolic risk factors. Further investigations particularly longitudinal studies with larger sample sizes are required to confirm these findings. SYSTEMATIC REVIEW REGISTRATION: identifier CRD42024600702.

INTRODUCTION: Kratom (Mitragyna speciosa) is a medicinal tree native to Southeast Asia. The present multilevel meta-analysis describes the association between kratom use and the positive and negative indicators of mental health. METHODS: A total of thirty-six articles were included in the meta-analysis to examine the associations, using a random-effects model. RESULTS: The pooled effect size showed a very small positive association between kratom use and negative indicators of mental health {r = 0.092, 95% confidence interval (CI) = [0.020, 0.164], p < 0.05}, while no significant association was found with positive indicators of mental health (r = -0.031, 95% CI = [-0.149, 0.087], p > 0.05). Pooled effect sizes of specific mental health outcomes indicated that kratom use showed only a small positive correlation with externalizing disorders (r = 0.201, 95% CI = [0.107, 0.300], p < 0.001). No significant association was found between kratom use and quality of life (r = 0.069, 95% CI = [-0.104, 0.242], p > 0.05) and internalizing disorders (r = -0.001, 95% CI = [-0.115, 0.095], p > 0.05). Multilevel moderator analysis showed that the pooled effect size of the association between kratom use and substance use disorder was stronger in Malaysia (r = 0.347, 95% CI = [0.209, 0.516], p < 0.001), and with the mean age (β1 = -0.035, 95% CI = [-0.055, -0.014], p = 0.003), and the drug profile of those who were not co-using other drugs (r = 0.347, 95% CI = [0.209, 0.516], p < 0.001). CONCLUSION: The meta-analysis supports the kratom instrumentalization concept, in that a positive gain from kratom consumption can be achieved without any significant adverse associations with mental health. © 2024 S. Karger AG, Basel.

OBJECTIVE: This review aims to synthesize and critically evaluate the existing literature on kratom use and its possible association with induction of psychotic and manic symptoms, in order to identify potential areas for future research that would improve our understanding of the risks of kratom consumption. METHODS: An electronic search was performed using five major databases: including PubMed, Scopus, Google Scholar, Web of Science, and PsycINFO. keywords such as kratom, Mitragyna speciosa, mania, psychosis, bipolar disorder, schizophrenia, schizoaffective, case report, and case series. The retrieved articles on initial search were screened based on predefined inclusion and exclusion criteria for this study, and then data synthesis was performed to analyze relevant information from the included studies. RESULTS: Six prior papers were found using (1 case series and 5 case reports). These included 10 cases, involving kratom use association with mania and psychosis. The ages of patients ranged from 28 to 55 years mean age was 38, and (SD 13.74), the majority were males (8 out of 11). Patients had durations of kratom use ranging from 2 wk to 15 years. Significant association was found between kratom use and the worsening of psychotic and manic symptoms in individuals with psychiatric conditions. CONCLUSIONS: Our research highlights the possibility of worsening preexisting psychiatric conditions in the context of kratom use. This study emphasizes the need for clinical evaluation of patients for kratom use. Additional research is required to gain a deeper understanding of the potential mental health implications of kratom use, especially among vulnerable populations.

Background: Kratom (Mitragyna speciosa Korth.) products are increasingly endorsed for self-management of multiple ailments, including as opioid substitution. The FDA has expressed that there is no evidence to indicate that this botanical is safe or effective for any medical use.Objective: We systematically review the current state of the literature concerning the impact of kratom and its alkaloids in all paradigms that involve opioids.Methods: A keyword search of online literature databases identified 16 preclinical studies, 25 case reports, and 10 observational studies meeting our pre-selected criteria.Results: All rodent models support alkaloids' action on opioid receptors, translating in their ability to mitigate opioid withdrawal. Some studies found mitragynine (MG) to have less reinforcing properties than morphine, and possessing tolerance-sparing properties when coadministered with morphine. Two studies that assessed 7-hydroxymitragynine (7OHMG) found it to substitute for morphine with potential for tolerance and dependence. Aside from addiction development, case reports outline a variety of confounding toxicities. Ten surveys of users, some conducted with assistance from pro-kratom lobbying organizations, find a high self-reported efficacy as an opioid substitute, with minimal reported adverse effects.Conclusion: With no reported controlled human clinical trials, in the light of rising concerns surrounding kratom's liabilities, there is insufficient evidence to allow any conclusions to be drawn. Case reports and observational studies carry significant bias toward harm and efficacy, respectively. Existing animal studies are heterogeneous in methodology and ultimately findings, with concern for interspecies variability and human translatability. Further research should investigate the safety and efficacy of using kratom alkaloids as opioid substitutes.

BACKGROUND: The legal status of kratom in the United States is complex and varies by state. The U.S. Food and Drug Administration (FDA) and the U.S. Drug Enforcement Administration have repeatedly subjected kratom to regulatory review. However, there hasn't been a systematic review of the public's perception of kratom. The present study analyzed open-ended responses from the public to an FDA solicitation for information regarding kratom with the goal of providing a comprehensive assessment of motives for kratom use. METHODS: To guide decisions regarding kratom regulation, the FDA solicited comments regarding kratom abuse potential, medical usefulness, and impact of scheduling changes from July through August 2021 and posted them to the Federal Register website. We analyzed comments posted during the first 6 weeks of comment solicitation (6,353) using an inductive approach via qualitative content analysis. RESULTS: Respondents reported 106 independent health-related reasons for kratom use, with most categorized as mental health, pain management, substance use disorder, or miscellaneous purposes that included increasing focus, treating insomnia, and decreasing fatigue. Neurological diseases and digestive disorders were also reported. Relatively few (< 2%) responses reported recreational use, abuse potential, or adverse effects of kratom. CONCLUSIONS: Although kratom is not approved as a safe and effective therapy for any indication, individuals use kratom for a broad spectrum of health-related purposes. Limitations of this study include potential bias for respondents with perceived positive experiences using kratom, lack of demographics data, and lack of independent verification of claims made by respondents. Regardless, this study reflects perceptions regarding the therapeutic uses of kratom and provides insight into potential individual-level consequences of regulating kratom in the U.S. It is important to study the public's perception of kratom use, which can aid regulatory purposes and provide clinically important information on individuals' use and valuation of kratom. Published by Elsevier B.V.

INTRODUCTION: Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic consumption. OBJECTIVE: Our study aims to investigate (pre)clinical evidence on the efficacy of kratom as a therapeutic aid and its safety profile in humans. METHODS: A systematic literature search using PubMed and the Medline database was conducted between April and November 2020. RESULTS: Both preclinical (N = 57) and clinical (N = 18) studies emerged from our search. Preclinical data indicated a therapeutic value in terms of acute/chronic pain (N = 23), morphine/ethanol withdrawal, and dependence (N = 14), among other medical conditions (N = 26). Clinical data included interventional studies (N = 2) reporting reduced pain sensitivity, and observational studies (N = 9) describing the association between kratom's chronic (daily/frequent) use and safety issues, in terms of health consequences (e.g., learning impairment, high cholesterol level, dependence/withdrawal). CONCLUSIONS: Although the initial (pre)clinical evidence on kratom's therapeutic potential and its safety profile in humans is encouraging, further validation in large, controlled clinical trials is required. © 2021 The Authors. Human Psychopharmacology: Clinical and Experimental published by John Wiley & Sons Ltd.

BACKGROUND AND OBJECTIVE: Kratom (Mitragyna speciosa) is a tropical tree found in southern Thailand and northern states of the Malay Peninsula. Kratom is commercially available and used as an alternative to treat opioid withdrawal. Mitragynine is the major indole alkaloid found in kratom leaves. This review aimed to summarize available pharmacokinetic information about mitragynine. METHODS: PubMed, Scopus, and Web of Science were systematically searched from their inceptions to June 2018. All types of pharmacokinetic studies of mitragynine were included for further systematic review. RESULTS: Seventeen articles were reviewed. Mitragynine is a lipophilic weak base passively transported across the intestinal wall and blood brain barrier. 85-95% is bound to plasma protein and extensively metabolized by phase I and particularly phase II enzymes. Actions on CYP enzymes are unlikely to impact drug metabolism at concentrations likely to exist in kratom-consuming humans. In rats and humans, mitragynine is rapidly absorbed after orally administration (Tmax˜1.5 h, Cmax˜0.3-1.8 μM). Vd was 37-90 L/kg; t1/2 was 3-9 hr; mostly excreted as metabolites in urine. Bioavailability was estimated as 21%. It also rapidly penetrated and redistributed in brain. A quality assessment tool tailored for pharmacokinetic studies was also created which rated some studies of lower value. CONCLUSION: Rudimentary pharmacokinetics of mitragynine was described in this systematic review. However, the discovered studies provided scant information on the role of metabolism and redistribution into tissues nor the rate of excretion.

BACKGROUND: Kratom (Mitragyna speciosa) is a psychoactive plant native to Southeastern Asia that is receiving increased international attention as a potential therapeutic agent. While much of the limited scientific research on kratom is focused on its analgesic potential, kratom use also has important risks and benefits in the domain of mental health. METHODS: We conducted a comprehensive systematic review of all studies on kratom use and mental health published between January 1960 and July 2017. RESULTS: Findings indicate kratom's potential as a harm reduction tool, most notably as a substitute for opioids among people who are addicted. Kratom also enhances mood and relieves anxiety among many users. For many, kratom's negative mental health effects - primarily withdrawal symptoms - appear to be mild relative to those of opioids. For some users, however, withdrawal is highly uncomfortable and maintaining abstinence becomes difficult. CONCLUSION: Results inform clinicians working in the mental health and substance use fields, policy-makers, and researchers about the mental health effects of this plant.

200. AORN J. 2026 May;123(5):362-370. doi: 10.1002/aorn.70077. Kratom Use: An Emerging Perioperative Nursing Concern. Vance BS, Miner L, Ostrowski A. Kratom is an emerging drug of concern that poses significant challenges in perioperative care, but the public and many health professionals remain unaware of its use and effects. Patients may use kratom as a substitute for opioids or to increase focus or decrease anxiety, depending on the dose. Kratom binds with μ-opioid, α2-adrenergic, and serotonin receptors and has been associated with perioperative complications, including difficulty managing pain, hemodynamic instability, agitation, and withdrawal symptoms in patients undergoing surgery. Considering that 1.9 million Americans aged 12 years and older have used kratom, screening patients before surgery is important. Preoperative nurses can positively affect patient care by communicating a patient's use of kratom to the care team. With that knowledge, perianesthesia, intraoperative, and postoperative teams can be prepared for any untoward effects of kratom use across all perioperative settings. © AORN, Inc, 2026.

Kratom (Mitragyna speciosa) is a traditional Southeast Asian botanical long used for alleviating pain and boosting energy. Its chief bioactive compound, mitragynine (MG), exhibits both opioid-like and stimulant properties and has prompted interest in its potential role in pain management and opioid withdrawal support. However, its safety profile and underlying mechanisms remain incompletely understood. This systematic review critically synthesizes preclinical evidence on kratom's molecular, pharmacological, and epigenetic effects. Guided by PRISMA 2020 criteria, studies indexed in Scopus and Web of Science (2000-2024) were analyzed, focusing on receptor activity, intracellular signaling, and gene regulation in in vitro and in vivo models. Among 20 eligible studies, key findings indicate that kratom alkaloids engage μ-opioid, adrenergic, and serotonergic receptors; modulate dopaminergic and glutamatergic systems; and exert anti-inflammatory and analgesic effects. Under chronic exposure followed by withdrawal, MG was associated with reduced histone acetylation and increased HDAC2 expression, while Rab35 emerged as a potential withdrawal-associated biomarker. MG also inhibited cardiac ion channels and altered CYP450 enzyme expression, highlighting safety concerns related to cardiotoxicity and drug-drug interactions. Despite these mechanistic insights, limitations in pharmacokinetic data, standardized dosing, and long-term safety preclude clinical application. Future research should prioritize controlled human studies, omics-driven biomarker discovery, and evidence-based regulatory evaluation to clarify kratom's therapeutic potential and risk profile. © 2026. The Author(s).

Kratom (Mitragyna speciosa Korth.) has gained increasing global attention due to its traditional use, psychoactive properties, and emerging therapeutic potential; however, concerns regarding adulteration, substitution, and inconsistent quality of commercial products necessitate robust authentication strategies. This study aimed to integrate DNA barcoding and comprehensive chemical profiling to authenticate kratom variants and discriminate them from closely allied Mitragyna species for quality control and forensic applications. Nine DNA barcoding regions were analyzed, alongside chemical characterization using UHPLC, GC-MS, and LC-MS/QTOF. Among the tested loci, the internal transcribed spacer (ITS) and ITS2 regions exhibited the highest interspecific variation and effectively distinguished kratom from allied species. UHPLC and GC-MS analyses confirmed that mitragynine was exclusively detected in kratom variants, with Kan Khiao exhibiting the highest content (94.33 ± 0.14 mg/g) when quantified against the mitragynine standard using UHPLC analysis. LC-MS/QTOF profiling revealed an alkaloid-rich chemotype in kratom dominated by mitragynine and 7-hydroxymitragynine, whereas M. diversifolia, M. hirsuta, and M. rotundifolia showed distinct profiles enriched in phenolic acids and flavonoid glycosides. Multivariate analyses further identified procyanidin B1, datiscetin-3-O-rutinoside, mitragynine, and 7-hydroxymitragynine as key discriminatory markers. Overall, the combined molecular and chemical workflow provides a robust framework for kratom authentication, supporting regulatory monitoring, quality assurance, and forensic identification of kratom materials.

Kratom (Mitragyna speciosa) is a commonly used over-the-counter supplement with opioid-like and dopaminergic activity. Cutaneous side effects have been incompletely characterized; only limited case reports describe its associated hyperpigmentation. We describe two cases of kratom-induced photodistributed brown-gray patches with biopsies that show circular, orange-brown granules in the dermis that stain positive with Fontana-Masson and negative for iron. In conjunction with existing literature, our cases suggest a possible distinct clinicopathologic pattern for which kratom use can be suspected. © 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

INTRODUCTION: Kratom (Mitragyna speciosa) contains over 50 alkaloids, yet the pharmacological activity of most remains poorly defined, limiting our understanding of its therapeutic potential and safety profile. METHODS: We conducted a comprehensive evaluation of both indole and oxindole alkaloids at human mu-, kappa-, and delta-opioid receptors (hMOR, hKOR, hDOR), integrating radioligand binding, cAMP inhibition, β-arrestin2 recruitment, [35S]GTPƔS assays, and molecular docking. RESULTS: While the activity of major alkaloids like mitragynine and 7-hydroxymitragynine is well documented, we report detailed functional and structural characterization of lesser-known kratom alkaloids, including epiallo-isopaynantheine, isopaynantheine, mitraciliatine, and isospeciofoline. These compounds exhibited diverse receptor selectivity and functional profiles, ranging from G protein-biased agonism to mixed MOR antagonism/KOR agonism. Notably, speciophylline demonstrated positive allosteric modulation at hMOR without direct orthosteric binding - a mechanism not previously demonstrated experimentally for kratom alkaloids at human opioid receptors. Several oxindole alkaloids showed potent hMOR agonism with minimal β-arrestin2 recruitment, representing an extreme G-protein signaling bias that distinguishes them from classical opioids. Structure-activity analysis identified conserved pharmacophoric elements at C15 and C20 that govern receptor affinity and functional profile across both indole and oxindole scaffolds. DISCUSSION: This systematic characterization at human opioid receptors reveals a pharmacologically diverse and structurally tunable class of natural products with potential as templates for developing opioid analgesics with improved therapeutic profiles.

The development of safer opioid therapeutics remains an urgent challenge, given the limitations and adverse effects of current μ-opioid receptor (MOR) agonists. Natural products such as mitragynine, the predominant alkaloid from Mitragyna speciosa (kratom), provide structurally complex scaffolds for probing MOR signaling bias and structure-activity relationships. However, enzymatic strategies for mitragynine modification remain largely restricted to native plant or non-native eukaryotic enzymes, which are often insoluble, low-yielding, or incompatible with heterologous expression, limiting their use for late-stage derivatization. Here, we establish a modular biocatalytic platform that repurposes noncognate oxidative enzymes for in vivo diversification of mitragynine. Using flavin-dependent monooxygenases (CtdE) and an orphan halogenase (D3) from Saccharophagus degradans, we achieved site-selective N-oxidation and C10 bromination, respectively, and demonstrate that these reactions can be combined in a single Escherichia coli host to perform sequential halogenation and oxidation directly from the parent alkaloid. The resulting analogues, including 10-bromo-mitragynine and its N-oxide, exhibit distinct MOR binding and G protein signaling profiles while failing to recruit β-arrestin. Collectively, these findings introduce a generalizable whole-cell platform for programmable, multistep alkaloid functionalization and highlight how biocatalysis can drive pharmacology to guide the discovery of novel bioactive scaffolds.

BACKGROUND: Mitragynine (MG), an alkaloid found in leaves of Mitragyna speciosa (kratom), is used for pain and opioid withdrawal. MG's effects are thought to be mediated through opioid receptors. The mu opioid antagonist naltrexone (NTX), indicated for the treatment of alcohol use disorder (AUD), reduces alcohol self-administration in animals. MG also alters alcohol consumption and alleviates alcohol withdrawal. Therefore, we tested MG, NTX, and both combined on alcohol self-administration in rats. METHODS: MG (0.3-3.0 mg/kg, IP) and NTX (0.3-3.0 mg/kg, IP) alone and the combinations of equal drug doses were evaluated in female Sprague Dawley rats lever pressing for alcohol (10%, w/v) under a fixed ratio 2 schedule of reinforcement. Numbers of active and inactive lever presses and estimated alcohol consumed were analyzed. Locomotor activity was assessed in separate groups of rats following MG, NTX (3.0 mg/kg), or its combination and their brains processed to determine cFos expression using immunohistochemistry. RESULTS: Both MG and NTX decreased alcohol self-administration, yet the combination had a greater effect than either alone and did not depress locomotor activity. Similarly, MG and NTX combined enhanced cFos expression in several brain regions more than either drug alone. CONCLUSIONS: MG decreased alcohol reinforcement more than NTX but the combination of the two was more impactful than either alone and engendered no adverse effects suggesting decreases in alcohol self-administration were not due to non-specific depression of activity levels. These data suggest that MG has a complex pharmacology that may involve mechanisms other than the mu opioid system.

We investigated the effects of varying light intensity and water availability on the foliar metabolome of Mitragyna speciosa (kratom) seedlings in a hydroponic settings. Untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics integrated with hierarchical orthogonal partial least squares discriminant analysis (OPLS-DA) was used to characterise the metabolite profiles. We obtained and annotated a total of 377 metabolites that spanned major ontologies such as alkaloids, flavonoids, terpenoids, phenolics/phenylpropanoids, and lipid derivatives. The highest number of unique metabolites was observed under high light (245), followed by low light (162), and medium light (110). Hierarchical OPLS-DA identified two significant splits within the metabolomic dataset, with light intensity as the primary determinant of metabolome variation (Split 1: Silhouette score = 0.52, P-value = 0.011), followed by water potential under low-light conditions (Split 2: Silhouette score = 0.51, P-value = 0.012). Exposure to high-light intensity lowered the abundance of nitrogen-based alkaloids like hirsuteine, corynoxeine, and ajmalicine, while increasing the abundance of photoprotective compounds like uncarine C, picrotin, and ursolic acid. Conversely, low light and low water availability resulted in a higher abundance of metabolites that included quercetin, alpha-tocopherol, magnoflorine, epigallocatechin, and curcumin, suggestive of a stress-induced antioxidant response. The findings can be used for optimizing bioactive metabolite production under controlled environments for pharmacological applications, though confirmation of certain compounds (e.g. magnoflorine and curcumin) in M. speciosa through future validation with authentic standards remains essential. © 2026 The Author(s) (or their employer(s)). Published by CSIRO Publishing.

BACKGROUND: Kratom ( Mitragyna speciosa ) is a plant indigenous to Southeast Asia. This pilot study evaluated the pharmacodynamic (PD) effects, safety, and pharmacokinetics (PK) of kratom and several of its alkaloids. METHODS: Recreational polydrug users (8 participants/cohort; 6 active: 2 placebo, N=40) completed the study. Participants had experience with opioids but were otherwise healthy. This study utilized a double-blind, between-subjects design where participants randomly received a single dose of placebo or kratom. The kratom used in the study had alkaloid levels representative of botanical kratom products (i.e., leaf) previously characterized in the literature and contained trace levels of 7-hydroxymitragynine (7-OH). The starting dose was 1 g and doses of 3, 8, 10, and 12 g were administered after safety reviews after each dose. After dosing, pupillometry and assessments of subjective effects were performed, and blood samples were collected. Safety assessments included adverse events (AE) monitoring, laboratory tests, vital signs, ECG assessments, physical examination findings, and assessment of suicidality. RESULTS: No deaths or serious adverse events (SAEs) occurred. Somnolence, vomiting, and nausea were the most common AEs reported. Kratom alkaloid concentrations showed generally orderly, dose-related effects. At doses ≥3 g, kratom produced pupillary constriction. Few dose-related effects were observed, although the 12 g dose of kratom produced increases on several subjective measures including ratings of "drug liking." CONCLUSIONS: This study investigated the safety of single-sourced botanical kratom; the results may not be representative of other kratom-containing products. Kratom produced some opioid-like effects including pupillary constriction, and the 12 g dose produced effects commonly associated with drugs of abuse such as visual analog scale (VAS) ratings of drug liking, good effects, and high.

7-Hydroxymitragynine (7-OH), a minor alkaloid in kratom (Mitragyna speciosa (Korth.) Havil.) (Rubiaceae) and an active metabolite of mitragynine, is a critical transient precursor to mitragynine pseudoindoxyl, which exhibits >2-fold μ-opioid receptor-biased agonism and improved isoform selectivity relative to its precursors. Although present only in trace amounts in kratom leaves, a recent survey identified hundreds of consumer products with semisynthetic 7-OH and mitragynine pseudoindoxyl. Their high potency, ease of access, and risk of addiction have prompted the US FDA to recommend scheduling 7-OH as a Schedule I controlled substance. To address this public health crisis and the associated analytical challenges, a comprehensive analysis of commercially available kratom products was performed. The results revealed substantial inconsistencies between the quantities claimed on the products' labels and the actual 7-OH amount detected in several of these products. Along with 7-OH and mitragynine pseudoindoxyl, several (over)oxidized byproducts were detected, providing crucial insights into their synthetic origins. Analysis of >98% of 7-OH-labeled products indicated a semisynthetic origin, with labeled doses ranging from 0.001 to 33.6 mg per serving. Furthermore, consistent with the prior report, 7-OH degrades into the potentially toxic byproduct 3-dehydromitragynine under simulated gastric conditions. These findings underscore significant safety concerns over oral 7-OH products and necessitate validated analytical monitoring to guide regulatory oversight and consumer protection.

This study investigates how soil calcium (Ca) and magnesium (Mg) supplementation influence mitragynine accumulation in Mitragyna speciosa (kratom), addressing the lack of quantitative thresholds in previous research. Seedlings from a uniform seed stock were cultivated in a controlled environment using a standardized soil mix (soil:peat moss:earthworm castings, 6:1:1). Following an initial growth phase, Ca and Mg were applied at three concentrations and in fixed Ca:Mg ratios (5:1, 10:1, 20:1) using gypsum and Epsom salt. Over a 45-day treatment period, growth parameters and mitragynine levels were assessed one week after the final application. Seedlings under control had the highest total biomass (102.35 g), significantly exceeding both the Mg-only and Ca:Mg treatments (64-84 g), and values above the typical upper threshold of 20 did not suppress growth, as evidenced by unchanged root-to-shoot ratios across treatments. In contrast, mitragynine accumulation was the highest under moderate Ca:Mg ratios (8-10), exhibiting a 2-14% increase relative to the control, suggesting that production of this alkaloid is more sensitive to nutrient balance than overall growth. These findings underscore the importance of nutrient ratios, rather than individual nutrient concentrations, in regulating both vegetative development and alkaloid production in kratom. Maintaining an appropriate Ca:Mg ratio can support efficient seedling growth as well as maximizing mitragynine levels. Preliminary field trials over a span of one month indicate that field-grown seedlings exhibit a similar result with high growth and mitragynine content in soils having a Ca:Mg ratio of 1:10. Future studies should test these responses under field conditions and over longer growth periods.

Piper methysticum, known as "kava", is a plant endemic to and historically consumed in the Pacific islands. The roots contain psychoactive kavalactones with sedating and anxiolytic effects. While often marketed for anxiety or as a safe alcohol alternative, dermopathy and more rarely hepatotoxicity are well described with heavy use. Reports of withdrawal are rare. The leaves of Mitragyna speciosa, also referred to as "kratom", contain psychoactive alkaloids with interactions at μ and δ-opioid receptors. Kratom is commonly used for its stimulant and opioid-like effects, for which dependence and withdrawal are much more well documented. A 45-year-old man presented to the emergency department (ED) with auditory and visual hallucinations, anxiety, insomnia, and diffuse muscle jerking. He had been heavily using a supplemental beverage containing both kava and kratom, but stopped several days prior. His primary physician initiated buprenorphine therapy for suspected kratom withdrawal. Bedside evaluation in the ED was concerning for ongoing GABAergic withdrawal in the setting of kava use. Phenobarbital was given with significant improvement in symptoms, with eventual transition to diazepam. He was discharged home several days later in good condition. Given the increasing popularity of herbal supplements including kratom, and more uncommonly kava, clinicians should be aware of their potential for abuse, dependence and severe withdrawal syndromes. Kratom may be managed in a fashion analogous to that of an opioid. While kava's pharmacologic properties remain poorly understood, withdrawal may be severe enough to warrant hospitalization. Phenobarbital or benzodiazepines may be considered as a potential therapeutic approach.

OBJECTIVE: The objective of the experiment was to study yeast supplementation (yeast, Y) and dried kratom leaves (DKTL) on the digestibility, ruminal fermentation, blood metabolites and nitrogen balance in goats. METHODS: Four of 7 to 8 months old male crossbred (50% Thai Native-Anglo Nubian) goats with average liveweight 20±0.13 kg were randomly assigned according to a 2×2 factorial arrangement in a 4×4 Latin square design to receive four diets ad libitum basis. The study investigated the effects of two levels of yeast (Y) supplementation (Y, 0 and 0.5g/kg dry matter [DM]) along with two levels of DKTL supplementation (DKTL, 0 and 4.44g/kg DM). The experimental groups were as follows: T1 = control group with 0Y+0DKTL, T2 = 0Y+4.44 DKTL, T3 = 0.5Y+0DKTL, and T4 = 0.5Y+4.44 DKTL. RESULTS: The results showed that there were no interactions between Y levels and DKTL levels with respect to total DM intake, but there were significant effects (p<0.05) by levels of Y; goats receiving 0.05 g/kg DM Y had higher than goats fed 0.0 g/kg DM on average (kg/d). A percentage of body weight (% BW) and grams per kilogram of metallic weight (g/kg w0.75) had no influence on yeast levels and DKTL, but there was a difference (p<0.05) by yeast level Y at 0.5 g/kg DM, being higher compared to the non-supplemented group. Apparent digestibility coefficient of nutrition in the form of (DM, organic matter, crude protein, neutral detergent fiber, and acid detergent fiber) was an increased trend in the Y-level complementary group at 0.5 g/kg DM and DKTL at 4.44 g/kg DM, respectively. Protozoa populations decreased in the group receiving Y levels at 0.5 g/kg DM and DKTL levels at 4.44 g/kg DM when compared to group T1. The acetic acid concentration and methane gas generation decreased (p<0.05) in the group receiving Y levels of 0.5 g/kg DM and DKTL levels of 4.44 g/kg DM, while the amount of propionic acid increased (p<0.05). CONCLUSION: Effects of feeding combinations of Y and DKTL supplementation on feed showed no interaction effect (Y×DKTL) on feed intake, rumen fermentation, bacterial and fungi population. The effect on protozoal populations was lower in the group that was supplemented w

OBJECTIVE: Mitragyna speciosa Korth is traditionally used in Thailand. They have a high level of antioxidant capacities and bioactive compounds, the potential to modulate rumen fermentation and decrease methane production. The aim of the study was to investigate the different levels of microencapsulated-Mitragyna leaves extracts (MMLE) supplementation on nutrient degradability, rumen ecology, microbial dynamics, and methane production in an in vitro study. METHODS: A completely randomized design was used to assign the experimental treatments, MMLE was supplemented at 0%, 4%, 6%, and 8% of the total dry matter (DM) substrate. RESULTS: The addition of MMLE significantly increased in vitro dry matter degradability both at 12, 24, and 48 h, while ammonia-nitrogen (NH3-N) concentration was improved with MMLE supplementation. The MMLE had the greatest propionate and total volatile fatty acid production when added with 6% of total DM substrate, while decreased the methane production (12, 24, and 48 h). Furthermore, the microbial population of cellulolytic bacteria and Butyrivibrio fibrisolvens were increased, whilst Methanobacteriales was decreased with MMLE feeding. CONCLUSION: The results indicated that MMLE could be a potential alternative plant-based bioactive compound supplement to be used as ruminant feed additives.

The alkaloid derivatives of Mitragyna speciosa, commonly known as kratom, pose a threat to society due to its potential for abuse, adverse reactions and tendency to be used as self-medication for opioid withdrawal, pain and mood disorders. A number of deaths have been reported along with complications such as respiratory depression, cardiopulmonary arrest, torsade de pointes and seizures. Its various effects and potential are yet to be fully studied. We describe the case of a healthy young male who presented with progressive respiratory failure requiring mechanical ventilation. Imaging revealed multifocal lung infiltrates while extensive infectious and cardiac work-up was negative. Based on the clinical course, a diagnosis of acute respiratory distress syndrome (ARDS) caused by kratom was made. The patient showed gradual clinical improvement and was weaned off supplemental oxygen. This case highlights yet another adverse reaction to kratom and the growing threat posed by its use. LEARNING POINTS: Kratom is a herbal supplement with opioid-like effects at high doses and stimulant effects at low doses.It is most commonly used to self-treat opioid withdrawal, mood disorders and pain.Acute respiratory distress syndrome (ARDS) is one of the adverse effects of kratom, which also include kratom withdrawal syndrome, seizures, rhabdomyolysis, torsades de pointes and sudden death.Kratom has growing abuse potential; the FDA is acting to prevent its use and recommends healthcare professionals voluntarily report any adverse reactions. © EFIM 2023.

This experiment evaluated the use of Mitragyna speciosa Korth leaf pellets (MSLP) on feed intake and nutrient digestibility in Thai native beef cattle. Four Thai native beef cattle steers were randomly assigned according to a 4 × 4 Latin square design to receive four dietary treatments. The treatments were as follows: control (no supplementation), MSLP supplement at 10 g/hd/d, MSLP supplement at 20 g/hd/d and MSLP supplement at 30 g/hd/d, respectively. All animals were fed a concentrate mixture at 0.5% body weight, while urea lime-treated rice straws were fed ad libitum. Findings revealed that feed intakes were increased by MSLP, which also significantly increased the digestibility of dry matter (DM), organic matter (OM) and neutral detergent fiber (NDF). Ruminal total volatile fatty acid (TVFA) concentration and propionate (C3) proportion were increased (p < 0.05) with MSLP supplementation, whereas ruminal ammonia-N (NH3-N), plasma urea nitrogen (PUN), acetate (C2), C2:C3 ratio and estimated methane (CH4) production decreased (p < 0.05). Total bacterial, Fibrobacter succinogenes and Ruminococus flavefaciens populations increased (p < 0.05) at high levels of MSLP supplementation, while protozoal populations and methanogenic archaea reduced (p < 0.05). Supplementation of MSLP also increased the efficiency of microbial nitrogen protein synthesis. Supplementing beef cattle with MSLP 10−30 g/hd/d significantly increased rumen fermentation end products and nutrient digestibility by mitigating protozoal populations and estimated CH4 production.

The objective of this study was to see how dried Mitragyna speciosa Korth leaves (DKTL) affected growth, hematological parameters, carcass characteristics, muscle chemical composition, and fatty acid profile in finishing goats. In a randomized complete block design, twenty crossbred males (Thai Native x Boer) weaned goats (17.70 ± 2.50 kg of initial body weight (BW)) were provided to the experimental animals (5 goats per treatment) for 90 days. Individual dietary treatments of 0, 2.22, 4.44, and 6.66 g/d of DKTL on a dry matter basis were given to the goats. The diets were provided twice daily as total mixed rations ad libitum. In comparison to the control diet, DKTL supplementation had no effect on BW, average daily gain (ADG), feed conversion ratio (FCR), carcass composition, meat pH, or meat color (p > 0.05). After DKTL treatment, the hot carcass weight, longissimus muscle area, oleic acid (C18:1n9), monounsaturated fatty acid (MUFA), and protein content increased, but saturated fatty acids (SFA) and ether extract decreased (p < 0.05). To summarize, DKTL supplementation can improve goat meat quality.

OBJECTIVE: Kratom is the pulverized dried leaves of the Mitragyna speciosa tree and has a bitter taste and high ingestion volume that repels children. Newer products use a single alkaloid extract from the leaves, mitragynine, or oxidize mitragynine to 7-hydroxymitragynine and place it in various oral dosage forms. We identified oral dosage form products containing mitragynine and/or 7-hydroxymitragynine that are marketed in ways that appeal to children and define their alluring characteristics. METHODS: We performed Google searches to identify websites selling kratom products. Products were assessed and included if they had 1 or more features that would be attractive to children and defined their formulations, alkaloids, flavoring/scents, mascots, and packaging. RESULTS: Eighty unique products that appealed to children were found, and 36.3% were gummies, 28.8% were tablets, 18.8% were drink mixes or liquids, 15.0% were miscellaneous candies (saltwater taffies, ice cream cones, noobs, popping crystals, honey sticks, mints, lollipops), and 1.3% were chocolates. Thirty-eight products (47.5%) contained mitragynine, 35 products (43.8%) contained 7-hydroxymitragynine, 6 products (7.5%) contained both, and 1 product (1.3%) did not specify which alkaloid was included. Twenty-six products (32.5%) had a cartoon mascot or symbol. Sixty-six products (82.5%) had brightly colored packaging, 59 products (73.8%) had brightly colored formulations, and 73 formulations (91.3%) had a flavor or scent. CONCLUSIONS: Mitragynine and 7-hydroxymitragynine are present in many products that could cause small children and teens to be exposed. Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: [email protected].

OBJECTIVES: Kratom ( Mitragyna speciosa ) is a psychoactive herbal product increasingly used for pain, anxiety, and opioid withdrawal. Although marketed as a natural dietary product, concerns have emerged regarding adverse effects like cardiotoxicity, seizures, opioid-like physical dependence, and, particularly, liver toxicity. METHODS: We conducted a systematic review following PRISMA 2020 guidelines of all studies on kratom use and liver toxicity. RESULTS: Thirty-one studies were included, comprising 32 cases of kratom-associated liver injury. Most reports originated from the United States and were single-patient case reports. Most patients were adult males, with frequent co-occurrence of polysubstance use and comorbid conditions. Concomitant exposures were commonly reported but variably characterized across studies. Baseline liver disease was present in 3 patients (9%). Kratom dose, form, frequency, and duration were inconsistently reported. Only 7 cases (22%) provided complete exposure details, whereas the remainder lacked one or more elements. Kratom use was temporally associated with the onset of liver injury, commonly presenting with jaundice and elevations in liver enzymes. The patterns of injury were predominantly cholestatic. In most cases, liver enzymes and function improved after cessation of kratom use. In 4 cases, the patient's liver function did not improve and progressed to liver transplantation. Although formal causality assessments were inconsistently reported, many reports supported an association based on exclusion of alternative etiologies and, in some cases, rechallenge episodes. CONCLUSIONS: Further research is needed to better characterize kratom's mechanisms of liver injury and to inform clinical decision-making and public health policy.

BACKGROUND: Kratom is a psychoactive botanical that is increasingly popular in the United States. While potential risks of kratom use have been identified, research on harm reduction strategies and contextual factors contributing to adverse reactions is limited. Given that kratom is federally unregulated at present, and a variety of kratom products are widely available on the commercial market, more data are needed to inform harm reduction efforts and public health messaging. METHODS: 102 participants (mean age = 22.34 years, 39.2% women) were recruited from ethnobotanical tea bars in Northern Colorado to complete a survey on kratom use, which included questions pertaining to adverse experiences. RESULTS: Most participants (75.5%) reported experiencing an adverse reaction to kratom at least once in the past, with a wide range of kratom doses reportedly consumed during these experiences. Adverse reactions were most commonly reported to occur in the context of consuming kratom on an empty stomach, consuming alongside certain foods, lack of hydration, and combining kratom with other substances. Participants employed a variety of strategies in attempt to mitigate adverse reactions, such as stopping or pacing their use of kratom and other substances, modulating hydration and food intake, and engaging in rest and recovery behaviors. CONCLUSIONS: Adverse reactions to kratom may be associated with certain contextual factors. Several techniques are reportedly used to mitigate adverse reactions, but the efficacy of these techniques is unknown. More data are needed to understand the causes and consequences of adverse reactions to kratom, and to better understand potential harm reduction strategies for reducing adverse experiences. More research could also shed light on the extent to which kratom serving size and various product formulations (e.g. whole leaf vs. extracts) are predictive of adverse effects. © 2026. The Author(s).