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Kratom refers to both Mitragyna speciosa, a tree native to Southeast Asia, and products manufactured from its leaves sold as herbal supplements. Kratom leaves contain a range of chemical compounds known as bioactive alkaloids, which have physiological effects. A mathematical model of the Kratom plant under a particular nutritional treatment will be provided in this research. Also, the methods for setting the initial condition and boundary condition will be presented. Also, as the plant grows, the solution's domain shifts every time. Techniques for adjusting the specific nutrient's physical parameters are also provided. With the use of an explicit finite difference method, the solutions are approximated. The specific nutritional concentrations are calculated for each height level. As shown, the specific nutrient will spread from the root to the apex of the trunk. The nutrient has the capacity to stimulate the growth of the Kratom. The specific nutrient concentration along the trunk may be measured using the proposed mathematical model as the Kratom plant grows each day. A proposed numerical model with a specific nutrient can be used to develop a precise model, such as a one-dimensional model of branches and foliage. It would be more captivating if the plant nutrients indicated here were researched for their ability to accelerate the growth of large or medium-sized Kratom plants. In conclusion, the study shows that calcium dihydrogen phosphate monohydrate may be useful as a growth promoter for Kratom plants and suggests a way to measure its effects quantitatively. [ABSTRACT FROM AUTHOR]

Introduction: Mitragyna speciosa (Korth.) or Kratom contains several bioactive compounds that have potential therapeutic benefits. The present study investigated the potential immunomodulatory effects of Mitragyna speciosa methanolic extract (MSME) in delayed-type hypersensitivity (DTH) mouse model. Materials and methods: Female Balb/c mice were induced with DTH by sheep red blood cells (SRBCs) following the administration of MSME. The thickness of paw edema that developed following subcutaneous injection of SRBC on the right hind footpad of the mice was measured. The blood samples and spleen were collected for investigation of the effects of MSME on antibody production, complete blood count (CBC), spleen index, splenocyte proliferation, and lymphocyte (CD4, CD8, and CD19) populations. Results: The data demonstrated that MSME significantly reduced the paw edema induced by SRBC and showed a marked reduction in anti-SRBC antibody levels. However, no significant changes were observed in the CBC, spleen index, and CD4, CD8, and CD19 subset populations. In addition, stimulation of splenocytes isolated from MSME-treated SRBC-induced DTH mice with lipopolysaccharide (LPS) or Concanavalin A (Con A) ex vivo reduced cell proliferation. Conclusion: These data demonstrated that MSME potentially inhibits immune response by suppressing DTH reactions, reducing antibody production and cell proliferation without affecting the lymphocyte profiles. These findings suggest the immunomodulatory effects of MSME through immunosuppressive and anti-inflammatory activities. [ABSTRACT FROM AUTHOR]

Kratom (Mitragyna speciosa), containing the primary alkaloid mitragynine, has emerged as an alternative self-treatment for opioid use disorder. Mitragynine binds numerous receptor types, including opioid receptors, which are known to modulate food consumption. However, the ability of acute mitragynine to modulate food consumption remains unknown. The current study assessed the effects of acute mitragynine or morphine administration on unconditioned food and water intake in 16 Sprague-Dawley rats. Food and water intake changes were monitored in response to morphine, mitragynine (1.78–56 mg/kg ip), saline, or vehicle controls for 12 h, starting at the onset of the dark cycle. Naltrexone pretreatment was used to examine pharmacological specificity. Both morphine and mitragynine demonstrated a biphasic food intake dose-effect, with low doses (5.6 mg/kg) increasing and high doses (56 mg/kg) decreasing food intake. All morphine doses reduced water intake; however, only the highest dose of mitragynine (56 mg/kg) reduced water intake. Naltrexone attenuated both stimulatory and inhibitory effects of morphine on food intake, but only the stimulatory effect of mitragynine. In conclusion, low doses of mitragynine stimulate food intake via opioid-related pathways, while high doses likely recruit other targets. NEW & NOTEWORTHY: This study reveals that morphine and the kratom alkaloid mitragynine produce dose-dependent effects on feeding in rats. Low doses stimulate food intake via opioid pathways, while high doses decrease consumption through nonopioid mechanisms. Morphine potently suppresses water intake at all doses, whereas only high doses of mitragynine reduce drinking. These findings provide novel insights into the complex opioid and nonopioid mechanisms underlying the effects of mitragynine on ingestive behaviors. [ABSTRACT FROM AUTHOR]

Cyclooxygenase (COX) and lipoxygenase (LOX) enzymes play a pivotal role in producing pro-inflammatory eicosanoids, including prostaglandins (PGs) and leukotrienes (LTs), in the inflammation process. Mitragynine is a primary alkaloid contained in the kratom's leaves and has been reported to show anti-inflammatory activity by suppressing COX-2 mRNA translation to lowering PGs synthesis. In this study, the Kratom's alkaloid extract containing ~ 46% mitragynine was found to exhibit dual inhibition activity towards COX-2/5-LOX enzymes at concentrations below 25 ppm in the LPS-induced RAW 264.7 macrophage cells. At these levels, no cell toxicity was observed while the cells became death (e.g., 10–46% viability at 50–100 ppm) and only COX-2 inhibition activity was observed after exposed with more than 25 ppm of alkaloid extract. In contrast, the methanolic-crude extract of Kratom's leaf containing ~ 5% mitragynine showed no inhibition toward COX-2/5-LOX enzymes and did not toxic onto the cells, even after treated at 100 ppm. The alkaloid extract suppressed several antiinflammation parameters, including ROS (64% reduction at 25 ppm), NO (30% reduction at 25 ppm), TNF-α (~ 50% reduction at 25 ppm), and IL-6 production (60% reduction at 6.25 ppm). In silico molecular studies indicated strong binding affinity of Kratom alkaloids to COX-2 and 5-LOX active sites, supporting the Kratom's alkaloids to have great potential dual inhibition activity towards COX-2/5-LOX enzymes and to be developed as a safer NSAIDs with fewer side effects. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) consumption is associated with aggression. Decoction derived from the kratom (Mitragyna speciosa Korth.) leaf has been used as a METH substitute in Southeast Asia. Given its perceived benefit, we investigated the relationship between kratom use and aggression in a treatment sample of METH users with and without kratom use history. Four hundred and three male METH users participated in this cross-sectional study. A semi-structured questionnaire and several objective clinical measures were administered. Results indicate that there were no significant differences in aggression and its dimensions between METH users with and without kratom use history. However, two distinct Clusters (1 and 2) of METH users with kratom use history were studied. Users in Cluster 1 were characterized by a higher quantity and frequency of daily kratom use, longer duration of kratom use, and use of kratom at a younger age. Users in Cluster 2 exhibited the opposite characteristics. Kratom dependence and the first age of kratom use were identified as risk factors for aggression in Cluster 1. The frequency of daily kratom use appeared as a protective factor against aggression in Cluster 2. The results offer partial support to the instrumental kratom use concept; lower frequency (1 to 3 times) of kratom use may potentially minimize aggression in METH users presenting with mild to moderate kratom dependence. [ABSTRACT FROM AUTHOR]

The rising prevalence of kratom use in the United States has led to increased encounters with individuals who consume kratom and those who develop Kratom Use Disorder (KUD) among healthcare professionals. This case series highlights the need for diverse treatment approaches tailored to the individual motivations for kratom consumption. Three cases are presented: one involving the progression from kratom use for energy to opioid-driven use with subsequent challenges in detoxification and transition to naltrexone necessitating buprenorphine low-dose induction for maintenance; another detailing successful inpatient detoxification using methadone and symptom-driven clonidine, followed by successful maintenance treatment with naltrexone; and a final case involving kratom consumption for pain and anxiety self-management by an individual without a history of addictive disorders, without meeting KUD criteria. These cases underscore the complexity of managing individuals who consume kratom as well as those who develop dependence, emphasizing the need for individualized treatment approaches considering various factors such as motivation for use, psychiatric comorbidities, and response to interventions. [ABSTRACT FROM AUTHOR]

Monoterpene indole alkaloids (MIAs) from Mitragyna speciosa ("kratom"), such as mitragynine and speciogynine, are promising novel scaffolds for opioid receptor ligands for treatment of pain, addiction, and depression. While kratom leaves have been used for centuries in South-East Asia as stimulant and pain management substance, the biosynthetic pathway of these psychoactives have only recently been partially elucidated. Here, we demonstrate the de novo production of mitragynine and speciogynine in Saccharomyces cerevisiae through the reconstruction of a five-step synthetic pathway from common MIA precursor strictosidine comprising fungal tryptamine 4-monooxygenase to bypass an unknown kratom hydroxylase. Upon optimizing cultivation conditions, a titer of ∼290 μg/L kratom MIAs from glucose was achieved. Untargeted metabolomics analysis of lead production strains led to the identification of numerous shunt products derived from the activity of strictosidine synthase (STR) and dihydrocorynantheine synthase (DCS), highlighting them as candidates for enzyme engineering to further improve kratom MIAs production in yeast. Finally, by feeding fluorinated tryptamine and expressing a human tailoring enzyme, we further demonstrate production of fluorinated and hydroxylated mitragynine derivatives with potential applications in drug discovery campaigns. Altogether, this study introduces a yeast cell factory platform for the biomanufacturing of complex natural and new-to-nature kratom MIAs derivatives with therapeutic potential. • De novo production of mitragynine and speciogynine in Saccharomyces cerevisiae achieved. • Five-step synthetic pathway reconstructed from strictosidine in yeast. • Optimized cultivation conditions yielded ∼290 μg/L of kratom MIAs from trehalose and glycerol. • Metabolomics analysis identified shunt products, highlighting enzyme engineering targets for further cell factory optimization. • Production of fluorinated and hydroxylated mitragynine derivatives demonstrated. [ABSTRACT FROM AUTHOR]

BACKGROUND: Kratom (Mitragyna speciosa) has a long history of traditional use. It contains various alkaloids and polyphenols. The properties of kratom's alkaloids have been well‐documented. However, the property of kratom's polyphenols in water‐soluble phase have been less frequently reported. This study assessed the effects of water‐soluble Mitragyna speciosa (kratom) extract (MSE) on gut microbiota and their metabolite production in fecal batch culture. RESULTS: The water‐soluble kratom extract (MSE0) and the water‐soluble kratom extract after partial sugar removal (MSE50) both contained polyphenols, with total phenolic levels of 2037.91 ± 51.13 and 3997.95 ± 27.90 mg GAE/g extract, respectively and total flavonoids of 81.10 ± 1.00 and 84.60 ± 1.43 mg CEQ/g extract. The gut microbiota in fecal batch culture was identified by 16S rRNA gene sequencing at 0 and 24 h of fermentation. After fermentation, MSE50 stimulated the growth of Bifidobacterium more than MSE0. MSE0 gave the highest total fatty acids level among the treatments. The phenolic metabolites produced by some intestinal microbiota during fecal fermentation at 24 h were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The major metabolite of biotransformation of both water‐soluble MSEs by intestinal microbiota was pyrocatechol (9.85–11.53%). CONCLUSION: The water‐soluble MSEs and their produced metabolites could potentially be used as ingredients for functional and medicinal food production that supports specific gut microbiota. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Mitragyna speciosa is a perennial plant native to Asia, well known for its psychoactive properties. Its major alkaloid mitragynine is known to have sedative and euphoric effects. Hence, the plant has been a subject of abuse, leading to addiction, necessitating efficient analytical methods to detect its psychoactive constituents. However, current chromatography‐based methods for detecting the alkaloids are time consuming and costly. Quantitative nuclear magnetic resonance (qNMR) spectroscopy emerges as a promising alternative due to its nondestructive nature, structural insights, and short analysis time. Hence, a rapid and precise qNMR method was developed to quantify selected major psychoactive alkaloids in various parts of M. speciosa. Mitragynine, specioliatine, and speciogynine were quantified in relation to the integral value of the ‐OCH3 groups of the alkaloids and the internal standard 1,4‐dinitrobenzene. The precision and reproducibility of the method gave a relative standard deviation (RSD) of 2%, demonstrating the reliability of the method. In addition, the method showed excellent specificity, sensitivity, high linearity range (R2 = 0.999), and limits of detection (LOD) and quantification (LOQ) values. The analysis revealed that the red‐veined M. speciosa leaves contained higher levels of mitragynine (32.34 mg/g), specioliatine (16.84 mg/g) and speciogynine (7.69 mg/g) compared to the green‐veined leaves, stem bark, or fruits. [ABSTRACT FROM AUTHOR]

Objectives: To estimate lifetime, past-year, and past-month prevalence of kratom, cannabis, and cannabidiol-only product use among adults 18 years and older in the United States, using 2 independent datasets. Methods: Utilizing (a) the 2022 National Survey on Drug Use and Health (NSDUH) and (b) a 2022 online national convenience sample of adults who use kratom regularly (from our research group at the National Institute on Drug Abuse [NIDA]), we examined key demographic information as well as lifetime, past-year, and past-month substance use and preferences. Results: Among the full sample of adults from the 2022 NSDUH, the prevalence of lifetime use was 49.69% for cannabis, 34.09% for cannabidiol-only products, and 1.93% for kratom.When solely examining participants who have used kratom, both independent datasets showed higher proportions of cannabis use over the lifetime-92.81% (95% confidence interval: 90.31-95.31) in the NSDUH subset and 92.16% (95% confidence interval: 89.37-94.95) in our NIDA sample. Conclusions: Our study demonstrates that people are co-using kratom with cannabis and/or cannabidiol-only products at the same time or during the same time period, though more research is needed to understand people's motivations and practices for such co-use. Co-use might result in herb-herb interactions that may impact research findings and clinical outcomes for people who use kratom. [ABSTRACT FROM AUTHOR]

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الملخص: أهداف البحث: نبات القرطوم، المعروف علميا باسم ميتراجينا سبيسيوزا، هو نبات طبي تقليدي من جنوب شرق آسيا، يحتوي على قلويد الميتراجينين كمركب رئيسي. ومثل النباتات الطبية الأخرى، له آثار جانبية وتأثيرات سمية موثقة في الدراسات العلمية وتقارير الحالات. يحظر بيع وحيازة القرطوم في ماليزيا لكنه قانوني في تايلاند. في الولايات المتحدة، لا يسوق القرطوم قانونيا كمنتج دوائي أو مكمل غذائي أو مضاف للأغذية التقليدية. رغم هذه القيود، يستمر الأفراد في تعاطي القرطوم ذاتيا لتخفيف مشاكل صحية متنوعة، غالبا دون فهم شامل للسميات المرتبطة به. طرق البحث: تم إجراء بحث مرجعي لجمع المعلومات الأساسية لهذه المراجعة. ركزت الدراسات المخبرية على إنزيمات الأيض، مشيرة بشكل غير مباشر إلى سمية القرطوم. في المقابل، أظهرت نتائج الدراسات على الحيوانات التأثيرات السمية المباشرة للقرطوم على الكبد والكلى والرئتين والدماغ. تضمنت دراسات الحالة، التي أجريت بشكل رئيسي في الدول الغربية، استخدام القرطوم منفردا أو مع مواد أخرى. النتائج: تشير الدراسات إلى وجود تأثيرات سمية متعددة للقرطوم على أعضاء الجسم المختلفة. وتؤكد دراسات الحالة هذه المخاطر من خلال توثيق حالات التسمم المختلفة. الاستنتاجات: تهدف هذه المراجعة إلى تعزيز الوعي بين المتخصصين في الرعاية الصحية وعامة الناس حول مخاطر القرطوم. كما يساعد تحديد الفجوات الحالية في توجيه الدراسات العلمية المستقبلية. وبما أن الوقاية خير من العلاج، تقدم هذه المراجعة معلومات شاملة عن السميات المرتبطة باستخدام أوراق القرطوم. Abstract: Mitragyna speciosa (Roxb.) Korth, locally known as kratom, is a traditional medicinal plant from Southeast Asia, with mitragynine as its principal alkaloid. Similar to other medicinal plants, kratom has side effects and toxicities, which have been documented in scientific studies and case reports. The mitragynine sale and possession of kratom are prohibited in Malaysia but legalized in Thailand. In the US, kratom is not lawfully marketed as a drug product, a dietary supplement, or a food additive in conventional food. Despite these restrictions, individuals continue to self-administer kratom to alleviate various health problems, often without a comprehensive understanding of the associated toxicities. Hence, the primary aim of this review is to provide a comprehensive overview of the toxicities associated with kratom, drawing from scientific studies, case reports, and other relevant sources. It also addresses the management of these toxicities, identifies gaps in existing studies, and discusses future perspectives. Therefore, a literature review search was conducted to gather essential information for this review. The in vitro studies focused on metabolizing enzymes, indirectly indicating kratom toxicity. By contrast, the in vivo results directly demonstrated kratom's toxic effects on the liver, kidneys, lungs, and brain. Case studies, primarily from Western countries, involved both single and combination use of kratom. Thus, by shedding light on these aspects, we aim to enhance awareness among healthcare professionals and the general public. Additionally, identifying existing gaps can guide future scientific studies. Since prevention is better than cure, this review holistically presents information about the toxicities associated with the use of kratom leaves, serving anyone seeking to understand and prevent kratom-related toxicities.

This research aims to develop valid and practical Liveworksheet-based interactive LKPD on the local biodiversity “Kratom” to support the P5 Project. This research method used research and development (R&D) with the 4D model consisting of 4 stages: Define, Design, Develop, and Disseminate. The developmental research was conducted at SMAN 3 Pontianak, with teachers and students in class X as the research subjects. The research instrument used an interview and a questionnaire with a Likert scale validity data analysis and a Guttman scale for practicality data analysis, which analyzed descriptively qualitative and quantitative. The results showed that the interactive E-LKPD developed a very valid category based on the validator's assessment of the material experts, with an average of 94.2%, media experts 96.3%, and linguistics 91.9%. Based on various factors such as appearance, presentation of materials, usefulness, and response to project-based learning activities. The results of the practicality of the student questionnaire response were 90% in the small-scale trial and 88.4% in the large-scale trial. So, the developed Liveworksheet-based interactive LKPD is categorized as very practical. Based on these findings, the development is categorized as very valid, very practical, and can be utilized in learning biology on biodiversity material to support P5 project.

Kratom (Mitragyna speciosa) is a psychotropic tropical plant that is used as a traditional remedy in Southeast Asia. It has many medicinal properties and has great potential for clinical applications. Mitragynine and 7-hydroxymitragynine (7-OH) are the important pharmacologically active compounds found in kratom with mitragynine as the major alkaloid found in the leaf. We report the development and validation of a high-performance liquid chromatography-photodiode array method for the determination and quantification of mitragynine from M. speciosa fresh leaf extract. Fresh leaf samples were cryogenically ground and freeze-dried before methanol extraction. Gradient elution was conducted using acetonitrile and ammonium bicarbonate buffer (pH 9.5) at a flow rate of 1 mL min-1. Chromatogram separation was achieved using Kinetex EVO C18 column in a duration of 25 min with MG eluted at 15.75 min. The calibration curves were in a linear relationship with determination coefficients (R2) = 0.99. Mitragynine quantification was calculated based on the calibration curve equation. The precision value (RSD) was less than 2% and accuracy range from 93%-100%. The values for limit of detection (LOD) and limit of quantification (LOQ) were 0.67 µg mL-1 and 1.51 µg mL-1, respectively. This method has been validated and found suitable for the quantification of mitragynine in fresh leaf. We found that freeze-drying during sample preparation from fresh leaf yielded more reliable mitragynine quantification, compared with that of conventional oven-drying method. [ABSTRACT FROM AUTHOR]

Background: While FDA-approved treatments exist for opioid use disorder, none are available for stimulant use disorder. Kratom (Mitragyna speciosa), an unregulated plant-derived substance with known opioid- and stimulant-like effects, has been used to self-treat opioid use disorder; however, its use in relation to stimulant use disorder has not been described. Objective: To understand whether and how individuals use kratom to self-treat stimulant use disorder. Methods: Using a commercially available social listening platform, 3,820 publicly available social media posts published between January 1, 2020, and June 21, 2021, were reviewed for relevance to kratom and stimulant discontinuation. Manual qualitative thematic analysis was conducted on relevant data. Results: Among the 398 relevant posts that discussed using kratom to discontinue stimulants, motivations and methods varied considerably. Posts predominantly identified benefits but also negative outcomes of kratom use. Some justified it as necessary despite consequences, while others reported a desire to quit. Conclusions: Although there is some awareness that kratom is used to self-treat opioid use disorder, its use to treat stimulant use disorder is more novel. In the absence of approved treatments, kratom was viewed as a natural and safe way to quit stimulants. Despite some reported success, this study shows self-treatment may pose significant risks, including kratom addiction and physical dependence. Healthcare practitioners, researchers, and public health professionals may benefit from understanding motivations for kratom use, associated benefits and risks, and the importance of discussing kratom use with patients/clients who have stimulant use disorder. [ABSTRACT FROM AUTHOR]

Background: Kratom, also known as Mitragyna speciosa, is a plant that originates in Southeast Asia and possesses unique pharmacological characteristics. It is commonly consumed in the form of tea made by boiling the leaves or using the leaves to create the powder. According to its pain-relieving effects, the prevalence of kratom use around the world has increased, which has various implications for healthcare providers. Mitragynine is a well-known active compound in kratom. Objective: This review aims to provide a comprehensive perspective on the cardiovascular effects of mitragynine and its potential cardiotoxicity through the literature. Method: Authors searched PubMed, Scopus, and Google Scholar databases using appropriate search strategies for each database. After the screening, all relevant studies were included. Results: Although kratom may have the potential for therapeutic benefits, it has been associated with multi-organ damage and cardiac toxicity in some cases. According to the available data, tachycardia and hypertension are the most common adverse effects. Other possible cardiovascular effects include atherosclerosis, ventricular arrhythmia, cardiomyopathy, dose-dependent prolonged QTc interval, myocarditis, cardiomegaly, and cardiopulmonary arrest. Conclusion: While prior research has indicated the possible negative effects of mitragynine overdose on the cardiovascular system, there are no definitive conclusions, and additional investigations are needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Kratom is commonly used by consumers, and the elemental impurity exposure that consumers would have at different kratom ingestion doses has been determined. Methods: This assessment used original data from independent third-party laboratory testing of kratom products to identify the percentage of products that exceeded permissible daily exposure limits for lead (5 µg/day), nickel (200 µg/day), arsenic (15 µg/day), and cadmium (5 µg/day), the interim reference level for lead in adults (12.5 µg/day), and the tolerable upper intake level for manganese (11 mg/day) and nickel (1 mg/day). We assessed all products regardless of type and then evaluated non-extract products, extract products, and a soda preparation separately for elemental impurities. Results: Three assessments of elemental impurities in kratom products have been published, totaling 68 products. Assessing all products and assuming a 3 g daily dose of kratom, 7.4% would exceed the permissible daily exposure limits for lead, 0% for nickel, 3.1% for arsenic, and 0% for cadmium. At a kratom dose of 25 g daily, 70.6% would exceed the permissible daily exposure limits for lead, 20.6% for nickel, 9.4% for arsenic, and 0% for cadmium. The interim reference level for lead would be exceeded by 1.5% of products at a kratom daily dose of 3 g and 33.8% of products at 25 g. The tolerable upper intake level for manganese would be exceeded by 12.5% of products at a kratom daily dose of 3 g and 41.7% of products at 25 g. Non-extract products generally contain greater concentrations of elemental impurities than extract products or the soda preparation. Discussion: Apart from their concentrations in a gram of product, assessing the amount of exposure to elemental impurities at different kratom ingestion doses is also important. Elemental impurities exceeding regulatory permissible concentrations for many products, especially with greater daily kratom ingestion doses, may impact human health. Conclusions: Some kratom products contain excessive concentrations of elemental impurities of toxicological concern, such as lead and arsenic. Non-extract products (powders, capsules, tablets) generally contain greater concentrations of elemental impurities than extract products or the soda preparation. Daily use of these products can result in exposures exceeding regulatory thresholds and adverse health effects. [ABSTRACT FROM AUTHOR]

Objective: Kratom use represents a growing risk for public health. The present study examined demographic and behavioral factors linked with kratom use. Participants: Participants were college students in the United States who participated in the 2019-2020 Healthy Minds Study. Methods: Participants completed survey-based assessment of kratom use and related demographic, behavioral, and mental health variables. Results: Kratom use was linked with being White, male or transgender/gender nonconforming, identifying as a sexual minority, use of alcohol or marijuana, and depressive symptoms. Kratom use was not uniquely linked to exercise or anxiety. Conclusions: The results of the present study can be used to inform initial targeting of efforts to reduce kratom use among college students. [ABSTRACT FROM AUTHOR]

In recent years, the online sale of kratom (Mitragyna speciosa), a Southeast Asian plant with both medicinal and psychoactive properties, has raised health concerns mainly due to the uncontrolled diffusion of adulterated kratom-related products. This exploratory study provides, for the first time, a snapshot of the availability of kratom products on the darknet which has been further validated by data searches on the surface web. A total of 231 listings of kratom across 23 darknet marketplaces were identified between March 2020 and October 2021. Among these, 40 were found actively sold across five markets by thirteen vendors. Listed items were mainly advertised as "safe" substitutes for medicinal products for the self-management of pain and other health conditions and offered in various forms (e.g., dry leaf powder, pills, capsules). Purchases were made using cryptocurrencies, with some vendors offering Pretty Good Privacy, and were shipped from Europe, Australia, the United States, and the United Kingdom. Goods sold by the same sellers also included illicit drugs and fraud-related products. Our study discovered a previously unknown diffusion of kratom products on the darknet mainly for self-treating a variety of medical conditions, suggesting the need for further research and immediate interventions to safeguard the well-being and health of kratom consumers. [ABSTRACT FROM AUTHOR]

The purpose of this study is to gain a better understanding of how the National Narcotics Agency (BNN) views the use of kratom plants by the Dayak community in West Kalimantan. In addition, the study also investigates the impact of proposed policies on public health and cultural practices. Interviews were conducted with BNN representatives, health experts, and members of the Dayak community. A qualitative approach was used to collect data through participant observation, document analysis, and in-depth interviews. To understand the context of the use of Kratom in the culture of the Dayak community, observations were made. Documentation includes BNN policies, scientific papers, and ethnographic records. The results showed that BNN identified Kratom as a plant with a risk of abuse and adverse health effects, which prompted strict regulations and bans. On the other hand, the Dayak community sees Kratom as an important part of their traditional medicine practice and worries that the ban will damage the tradition and negatively impact their health. Health experts propose a more balanced policy, which involves strict regulation, effective oversight, and community education programs. This research suggests culturally sensitive and licensing policies for Kratom use. The goal is to strike a balance between maintaining public health and respecting local wisdom. [ABSTRACT FROM AUTHOR]

Background: Kratom/ketum is a psychoactive herbal preparation that has been used for a long time as a remedy and performance-enhancing substance in Southeast Asia. The advancement of globalization is making kratom increasingly more available in the western world, where it is becoming increasingly more used. Objective: The current research on kratom and its ingredients is presented. Material and methods: An overview of the use and effects of kratom is exemplary given on the basis of reports. The instrumentalization of the drug and its consequences up to the development of addiction are discussed. Results: Consumption is accompanied by several instrumentalizeable effects so that kratom is used as a therapeutic substance in the self-management of pain, anxiety and depression as well as other substance addictions. Another benefit comes from the performance-enhancing effects on physical work and in a social context. Consumption is usually well controlled, rarely escalates and has few and mostly mild aversive side effects. The danger arises from consumption particularly when there is an escalation of the dose and from mixed consumption with other psychoactive substances. The main alkaloid mitragynine and the more potent 7‑hydroxy-mitragynine are considered mainly responsible for the effect. Both have a complex pharmacology that involves partial µ‑opioid receptor agonism. Discussion: Epidemiological, clinical and neurochemical studies have shown that kratom only has a limited addictive drug profile, which might suggest a medical use as a remedy or substitute in addiction treatment. [ABSTRACT FROM AUTHOR]

Background: Kratom is a substance that alters one's mental state and is used for pain relief, mood enhancement, and opioid withdrawal, despite potential health risks. In this study, we aim to analyze the social media discourse about kratom to provide more insights about kratom's benefits and adverse effects. Also, we aim to demonstrate how algorithmic machine learning approaches, qualitative methods, and data visualization techniques can complement each other to discern diverse reactions to kratom's effects, thereby complementing traditional quantitative and qualitative methods. Methods: Social media data were analyzed using the latent Dirichlet allocation (LDA) algorithm, PyLDAVis, and t-distributed stochastic neighbor embedding (t-SNE) technique to identify kratom's benefits and adverse effects. Results: The analysis showed that kratom aids in addiction recovery and managing opiate withdrawal, alleviates anxiety, depression, and chronic pain, enhances mood, energy, and overall mental well-being, and improves quality of life. Conversely, it may induce nausea, upset stomach, and constipation, elevate heart risks, affect respiratory function, and threaten liver health. Additional reported side effects include brain damage, weight loss, seizures, dry mouth, itchiness, and impacts on sexual function. Conclusion: This combined approach underscores its effectiveness in providing a comprehensive understanding of diverse reactions to kratom, complementing traditional research methodologies used to study kratom. [ABSTRACT FROM AUTHOR]

Background There is an increase in the sale of legal drugs in our country. One of these substances is kratom. Kratom (Mitragyna speciosa) is a partial agonist of the opioid kappa, mu, and delta receptors. It acts as a stimulant at low concentrations, making users feel more energetic and euphoric. It has sedative and antinociceptive effects at higher doses. Case summary An 18-year-old man collapsed during football training and required cardiopulmonary resuscitation; the initial rhythm was ventricular fibrillation managed by defibrillation. Laboratory parameters were unremarkable. Blood samples sent for toxicological evaluation were positive for kratom and caffeine. Echocardiographic examination, coronary computed tomography angiography, and cardiac magnetic resonance imaging did not prove the cause. Genetic testing did not find a pathogenic gene variant associated with familial ventricular fibrillation, but a variant of unknown significance was found in MYOM1. Given this situation, we implanted an implantable cardioverter-defibrillator (ICD) from the secondary prevention of sudden cardiac death (SCD) according to the guidelines of the European Society of Cardiology (ESC). No recurrence of ventricular arrhythmia has been reported by ambulatory ICD memory checks on our patient. Discussion In some country, kratom is freely available and sold as a plant, not a drug. Only incident cases of ventricular fibrillation after kratom use are described in the literature. There is insufficient scientific evidence linking kratom to ventricular fibrillation. This is an absolutely crucial case report of this type, which has not yet been published in similar circumstances in the world. Therefore, the development of ventricular fibrillation was assumed to be due to a combination of kratom, caffeine, and exercise. The safety profile and effects of kratom should be the subject of future research. We would like to stress the importance of reporting further case series for more scientific evidence and thus increasing the pressure for stricter availability and regulation of kratom in some countries, especially where it is over-the-counter. [ABSTRACT FROM AUTHOR]

One of the kratom (Mitragyna speciosa Korth.) products in Kapuas Hulu is fermented kratom tea powder, produced by the enzymatic oxidation process, which is very different from the processing of black tea. Until now, there has been no research on the manufacture of fermented kratom tea powder using the black tea enzymatic oxidation method. This study aimed to determine the differences between the enzymatic oxidation method to the antioxidant activity of water extract kratom tea. The technique used in this study was a comparative method to compare the data obtained from water extract kratom tea. The treatments compared were the manufacture of fermented kratom tea powder with the enzymatic oxidation method of the Kapuas Hulu community and the enzymatic oxidation method of black tea. The parameters tested in this study consisted of phenol content, flavonoid content, alkaloid content, and antioxidant activity. The study showed that the phenol and alkaloid contents were higher in product of black tea methods (199.22 mg GAE/g and 44.73%) than Kapuas Hulu traditional methods (50.45 mg GAE/g and 40.68%). Flavonoid content was higher in Kapuas Hulu traditional methods (169.32 mg QE/g) than black tea methods (48.77 mg QE/g). The difference was found in the antioxidant activity of the water extract kratom tea produced by two different enzymatic oxidation methods. The enzymatic oxidation of the black tea method was found to higher antioxidant activity of water extract kratom tea.

Mitragyna speciosa, commonly known as kratom, is a narcotic plant that is used for its unique mood‐enhancing and pain‐relieving effects. It is marketed throughout the United States as a 'legal high' and has gained popularity as an alternative to opioids. However, kratom's increasing involvement in accidental overdoses, especially among polydrug users, has prompted warnings from the Drug Enforcement Agency (DEA) and the Food and Drug Administration (FDA). Despite these warnings, kratom remains legal federally, although it is banned in six states. This legal disparity complicates monitoring and enforcement efforts in states where kratom is illegal. Common forensic techniques using morphology or chemical analysis are beneficial in some instances but are not useful in source attribution because most seized kratom is powdered and the alkaloid content of samples can vary within products, making sourcing unreliable. This study focused on developing a DNA barcoding method to access sequence variation in commercial kratom products. It evaluated the utility of one nuclear barcode region (ITS) and three chloroplast barcode regions (matK, rbcL, and trnH‐psbA) in assessing sequence variation across commercially available kratom products. Novel polymorphisms were discovered, and the ITS region showed the greatest variation between samples. Among the 15 kratom products tested, only two haplotypes were identified across the four barcoding regions. The findings highlight the potential of DNA barcoding as a forensic tool in the traceability and enforcement against illegal kratom distribution. Nonetheless, the limited haplotypic diversity points to a need for further development and expansion of the M. speciosa DNA sequence database. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Kratom is a natural psychoactive product known primarily in Southeast Asia, including Thailand, Malaysia, etc. It is also known as krathom, kakuam, ithang, thom (Thailand), biak-biak, ketum (Malaysia) and mambog (Philippines) and is sometimes used as an opium substitute. It is stimulant at doses of 1–5 g, analgesic at doses of 5–15 g and euphoric and sedative at doses of >15 g. Mitragynine is the most abundant indole compound in kratom (Mitragyna speciosa) and is metabolized in humans to 7-hydroxymitragynine, the more active metabolite. Adverse effects include seizures, nausea, vomiting, diarrhea, tachycardia, restlessness, tremors, hallucinations and death. There are few studies on the analytical method for the detection of mitragynine and 7-hydroxymitragynine in hair. Therefore, this study proposes a liquid chromatography–tandem mass spectrometry (LC–MS-MS) method for the analysis of kratom in hair. Hair samples were first weighed to ∼10 mg and washed with methanol. Then the washed hair samples were cut into pieces and incubated in methanol with stirring and heating (16 h/38℃). Extracts were then analyzed by LC–MS-MS. This method was validated by determining the limit of detection (LOD), limit of quantification, linearity, intra- and inter-day accuracy and precision, recovery and matrix effects. The intra- and inter-day precision (CV%) and accuracy (bias%) were within ±20%, which was considered acceptable. Using this newly developed LC–MS-MS method, the simultaneous detection of mitragynine and 7-hydroxymitragynine in six authentic hair samples was achieved to provide the direct evidence of kratom use in the past. Mitragynine concentrations ranged from 16.0 to 2,067 pg/mg (mean 905.3 pg/mg), and 7-hydroxymitragynine concentrations ranged from 0.34 to 15 pg/mg (mean 7.4 pg/mg) in six authentic hair samples from kratom abusers. This may be due to the higher sensitivity of the LOD in this study, with values of 0.05 pg/mg for mitragynine and 0.2 pg/mg for 7-hydroxymitragynine in hair. [ABSTRACT FROM AUTHOR]

Limited research has resulted in conflicting views on the risks versus benefits associated with kratom use. Despite no federal policy in the United States, individual states have implemented diverging policies through kratom bans, and legalization and regulation through Kratom Consumer Protection Acts (KCPAs). The Survey of Non-Medical Use of Prescription Drugs (NMURx) Program employs nationally-representative, repeated cross-sectional surveys on drug use. In 2021, weighted prevalence of past−12 month kratom use was compared across three state legal frameworks: no overarching state policy, KCPAs, and state bans. There was lower estimated prevalence of kratom use in banned states (prevalence: 0.75% (0.44, 1.06) relative to states with a KCPA (1.20% (0.89, 1.51)), and relative to states with no policies (1.04% (0.94, 1.13), though odds of use were not significantly associated with policy type. Kratom use was significantly associated with medicated treatment for opioid use disorder. While there were observed differences in the prevalence of past−12 month kratom use by state policy type, low uptake mitigated meaningful distinctions by limiting statistical precision, and potentially confounding effects, such as accessibility online. Future kratom-related policy decisions should be informed through evidence-based research. [ABSTRACT FROM AUTHOR]

This study aimed to develop an antioxidative compound extraction method for Kratom (Mitragyna speciosa) leaves using cellulase and pectinase, in combination and alone. The enzymatic hydrolysis-assisted process (EA) successfully enhanced antioxidant extraction from kratom leaves. The single enzymatic hydrolysis-assisted process (SEA) with 6% cellulase (C6) provided the highest extraction yield. The mixed enzymatic hydrolysis-assisted process (MEA) was then developed using C6, mixed with different concentrations of pectinase. Based on the high extraction yield, the MEA using 6% cellulase and 2% pectinase (C6+P2) was selected for further studies in comparison with that from relevant SEA and the control (without EA). Different extraction processes altered the characteristics and antioxidative activities of resulting extracts. The antioxidative activity of C6+P2 was dramatically enhanced in the gastrointestinal tract model system. Fourier transform infrared (FT-IR) spectrometer results confirmed significant content of phenolic compounds, proteins, and polysaccharides in C6+P2. From in vitro cytotoxicity study, C6+P2 showed an IC 50 value of 22.86 and 4.76 µg/mL in RAW264.7 and Caco-2 cells, respectively. The bioactive compounds from C6+P2 should be identified in further studies to facilitate their application in the food and pharmaceutical industries. [Display omitted] • 6% Cellulase mixed with 2% pectinase (C6+P2) gave the highest extraction yield. • C6+P2 showed drastically increase in antioxidative activity after digestion. • FTIR spectra reconfirmed the complex form of antioxidative compounds. • Cytotoxicity of C6+P2 was evaluated as IC 50 on macrophage and epithelial cells. [ABSTRACT FROM AUTHOR]

The opioid epidemic and limited access to treatment for opioid withdrawal (OW) and opioid use disorder (OUD) has led individuals to seek alternative treatments. This narrative review aims to educate clinicians on the mechanisms of action, toxicity, and applications of psychoactive plant-based substances patients may be using to self-treat OUD and OW. We specifically discuss ayahuasca, ibogaine, and kratom as they have the most evidence for applications in OUD and OW from the last decade (2012-2022). Evidence suggests these substances may have efficacy in treating OW and OUD through several therapeutic mechanisms including their unique pharmacodynamic effects, rituals performed around ingestion, and increased neuroplasticity. The current evidence for their therapeutic application in OUD and OW is primarily based on small observational studies or animal studies. High-quality, longitudinal studies are needed to clarify safety and efficacy of these substances in treatment of OW and OUD. [ABSTRACT FROM AUTHOR]

The objective of this research was to study the diversity of kratom subpopulation in the Southern Thailand using morphological characteristics for classification. Study on kratom specimens in 9 provinces in the area of Southern Thailand: Surat Thani, Nakhon Si Thammarat, Trang, Phatthalung, Krabi, Phang Nga, Chumphon, Prachuap Khiri Khan and Ranong. Record of ecosystem and morphological characteristics. Data were analyzed and a dendrogram using the UPGMA technique. It was found that kratom can be divided into 2 large groups: 1) Group of green petiole includes green, yellow-green and green-yellow colors 2) group of red petiole includes red, red-orange, pink-orange colors. Leaf shape can be classified into 3 types: lanceolate, obvate and obovate. Leaf base can be classified into 3 types: cuneate, obtuse and cordate. Leaf apex can be classified into 2 types: cuminate and cuspidate. Leaf margin can be classified into 2 types: entire and dentate. Stipule color can be classified into 3 groups: green and yellow-green group, orange-pink and pink-orange group and red-orange and red group. Therefore, it can be indicated that the Southern Thailand has a wide variety of kratom population with morphological differences. [ABSTRACT FROM AUTHOR]

Background and Purpose: Kratom is a preparation from Mitragyna speciosa, which is used as a natural drug preparation for many purposes around the world. However, an overdose of Kratom may cause addiction‐like problems including aversive withdrawal states resulting in cognitive impairments via unknown mechanisms. Its main psychoactive alkaloid is mitragynine, showing opioid‐like properties. Experimental Approach: Here, we analysed the neuropharmacological effects of mitragynine compared with morphine withdrawal in rats and searched for a pharmacological treatment option that may reverse the occurring cognitive deficits that usually aggravate withdrawal. Key Results: We found that withdrawal from 14‐day mitragynine (1–10 mg·kg−1·day−1) treatment caused dose‐dependent behavioural withdrawal signs resembling those of morphine (5 mg·kg−1·day−1) withdrawal. However, mitragynine (5 and 10 mg·kg−1·day−1) withdrawal also induced impairments in a passive avoidance task. Mitragynine withdrawal not only reduced hippocampal field excitatory postsynaptic potential (fEPSP) amplitudes in basal synaptic transmission and long‐term potentiation (LTP) but also reduced epigenetic markers, such as histone H3K9 and H4K12 expression. At the same time, it up‐regulates HDAC2 expression. Targeting the epigenetic adaptations with the HDAC inhibitor, SAHA, reversed the effects of mitragynine withdrawal on epigenetic dysregulation, hippocampal input/output curves, paired‐pulse facilitation, LTP and attenuated the cognitive deficit. However, SAHA amplified the effects of morphine withdrawal. Conclusion and Implications: The data from this work show that changes in histone expression and downstream hippocampal plasticity may explain mitragynine, but not morphine, withdrawal behaviours and cognitive impairments. Thus, it may provide a new treatment approach for aversive Kratom/mitragynine withdrawal and addiction. [ABSTRACT FROM AUTHOR]

The Kratom plant, a valuable forest species with medicinal potential, thrives in the Riparian area of Empangau Village, Kapuas Hulu District. This study explores the correlation between Kratom cultivation land distance from the river and alkaloid content. Employing a survey method, the research focuses on two locations: one situated 20-50 meters from the river (location 1) and another 580-650 meters away (location 2). Utilizing a quantitative approach and gravimetric methods, the study analyzes alkaloid content in Kratom extracts. The study reveals significant influences on pH, organic carbon, total nitrogen, phosphorus (P2O5), calcium, magnesium, potassium, sodium, cation exchange capacity (CEC), base saturation, and alkaloid compounds, contingent on the distance from the riparian area. Location 2 exhibits superior attributes, boasting a plant height of 6.02 m, stem diameter of 8,532 m2, 30 primary branches, leaf area of 262,576, and a total alkaloid content of 15,491%, surpassing location 1 with an average plant height of 5.66 m, stem diameter of 8,286 m2, 26.6 primary branches, and leaf area of 257,586. Variations in environmental conditions, vegetation, temperature, humidity, and nutrient availability contribute to these differences in alkaloid growth and quality, highlighting the potential for optimized Kratom cultivation in specific Riparian areas. [ABSTRACT FROM AUTHOR]

Background: "Kratom" refers to an array of bioactive products derived from Mitragyna speciosa, a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and common reasons for use are to address mental and physical health needs, manage pain, and to reduce use of other substances. Natural-history studies and survey studies suggest that many kratom consumers perceive benefits from those uses, but such studies are unlikely to capture the full range of kratom-use experiences. Methods: We collected text data from Reddit posts from 2020-2022 to qualitatively examine conceptualizations, motivations, effects, and consequences associated with kratom use among people posting to social media. Reddit posts mentioning kratom were studied using template thematic analysis, which included collecting descriptions of kratom product types and use practices. Network analyses of coded themes was performed to examine independent relationships among themes, and between themes and product types. Results: Codes were applied to 329 of the 370 posts that comprised the final sample; 134 posts contained kratom product descriptions. As Reddit accounts were functionally anonymous, demographic estimates were untenable. Themes included kratom physical dependence (tolerance, withdrawal, or use to avoid withdrawal), perceived addiction (net detrimental effects on functioning), and quitting. Extract products were positively associated with reports of perceived addiction, dependence, and experiences of quitting kratom. Many used kratom for energy and self-treatment of pain, fatigue, and problems associated with opioid and alcohol; they perceived these uses as effective. Consumers expressed frustrations about product inconsistencies and lack of product information. Conclusion: As in previous studies, kratom was deemed helpful for some and a hindrance to others, but we also found evidence of notable negative experiences with kratom products that have not been well documented in surveys. Daily kratom use may produce mild-moderate physical dependence, with greater severity being possibly more common with concentrated extracts; however, there are currently no human laboratory studies of concentrated kratom extracts. Such studies, and detailed kratom product information, are needed to help inform consumer decision-making. [ABSTRACT FROM AUTHOR]

AbstractThailand removed kratom from the list of prohibited substances in 2021, possession and consumption of Kratom is now legal. It is prohibited from selling Kratom to anyone under the age of 18 and/or who is pregnant or breastfeeding. While there are benefits from kratom use with few reported adverse effects, escalating dose and increased use frequency raise the risk for toxic events in the setting of polysubstance use or development of a use disorder. We utilized data from the Behavior Surveillance Survey in Bangkok (n = 5,740) to examine the use of kratom with other substances use in the 12 months before the survey. The prevalence of past-year kratom use among students was 9.3% (95%CI = 8.7–9.9), with higher proportions of males (12.4 versus 6.1%, p < 0.001). The factors associated with past 12-month kratom use were academic performance (Medium GPA; AOR = 2.41, 95% CI = 1.76–3.29; Low GPA; AOR = 4.15, 95% CI = 2.94–5.87), close friend use substance (AOR = 1.94, 95% CI = 1.44–2.59), cannabis use (AOR = 6.84, 95% CI = 4.61–10.15), consumed alcohol (AOR = 2.32, 95% CI = 1.77–3.02), smoked conventional cigarettes (AOR = 4.20, 95% CI = 3.16–5.58), used e-cigarettes (AOR = 4.37, 95% CI = 3.30-5.79) used illicit opioids (AOR = 8.13, 95% CI = 4.35–15.18), and other illicit drug use (AOR = 9.15, 95% CI = 3.78–22.14). These findings may be useful for the initial targeting of efforts to reduce adolescent consumption of kratom. Future studies should examine the effect of regulatory policies or other Thai FDA-related policies use of illicit drugs and e-cigarettes on kratom use. [ABSTRACT FROM AUTHOR]

Although kratom use has been part of life for centuries in Southeast Asia, the availability and use of kratom in the United States (US) increased substantially since the early 2000s when there was little information on kratom pharmacology, use patterns, and effects, all critical to guiding regulation and policy. Here we provide a synthesis of research with several hundred English-language papers published in the past 5 years drawing from basic research, epidemiological and surveillance data, and recent clinical research. This review of available literature aims to provide an integrated update regarding our current understanding of kratom's benefits, risks, pharmacology, and epidemiology, which may inform United States-based kratom regulation. Recent surveillance indicates there are likely several million past-year kratom consumers, though estimates vary widely. Even without precise prevalence data, kratom use is no longer a niche, with millions of United States adults using it for myriad reasons. Despite its botanical origins in the coffee tree family and its polypharmacy, kratom is popularly characterized as an opioid with presumed opioid-system-based risks for addiction or overdose. Neuropharmacology, toxicology, and epidemiology studies show that kratom is more accurately characterized as a substance with diverse and complex pharmacology. Taken together the work reviewed here provides a foundation for future scientific studies, as well as a guide for ongoing efforts to regulate kratom. This work also informs much-needed federal oversight, including by the United States Food and Drug Administration. We conclude with recommendations for kratom regulation and research priorities needed to address current policy and knowledge gaps around this increasingly used botanical product. [ABSTRACT FROM AUTHOR]

Objectives: Kratom leaf products are increasingly consumed in the United States, with many consumers reporting they experience beneficial effects from kratom use. However, there is a growing concern for kratom's potential to result in dependence when used regularly. As such, we sought to assess, using Diagnostic and Statistical Manual of Mental Disorders , (DSM-5) , diagnostic criteria for substance use disorder, the prevalence of "kratom use disorder" (KUD) among kratom consumers. Methods: Our cross-sectional study used an online, anonymous survey between February and May 2023. Through nonprobability sampling, we recruited people older than 18 years who currently consume kratom. Participants were asked about their kratom consumption patterns, adverse effects perceived to stem from kratom consumption, comorbid diagnoses, and components for a DSM-5 , substance use disorder, adapted for kratom. Results: Among the total sample (N = 2061), KUD criteria were met by 25.5% of participants (n = 525); the most commonly reported symptoms were tolerance (n = 427, 81.3%) and withdrawal (n = 357, 68.0%). After adjusting for age, gender, daily frequency of kratom consumption, and history of either a substance use disorder or a mental health condition, those with a concurrent diagnosis of another substance use disorder had 2.83 times higher odds of meeting KUD criteria (95% CI, 2.19–3.67) compared with those without one. Conclusions: In this large cross-sectional study, most participants who met the criteria for a KUD diagnosis were categorized as having a mild or moderate KUD. Individual characteristics associated with KUD were related to being male, young, consuming kratom frequently, and having psychiatric and substance use disorder comorbidities. [ABSTRACT FROM AUTHOR]

Despite widespread kratom use, there is a lack of knowledge regarding its effects on driving. We evaluated the self-reported driving behaviors of kratom consumers and assessed their simulated-driving performance after self-administering kratom products. We present results from: 1) a remote, national study of US adults who regularly use kratom, and 2) an in-person substudy from which we re-recruited participants. In the national study (N = 357), participants completed a detailed survey and a 15-day ecological momentary assessment (EMA) that monitored naturalistic kratom use. For the remote study, outcomes were self-reported general and risky driving behaviors, perceived impairment, and driving confidence following kratom administration. For the in-person substudy, 10 adults consumed their typical kratom products and their driving performance on a high-fidelity driving simulator pre- and post-kratom administration was evaluated. Over 90% of participants surveyed self-reported driving under the influence of kratom. Most reported low rates of risky driving behavior and expressed high confidence in their driving ability after taking kratom. This was consistent with EMA findings: participants reported feeling confident in their driving ability and perceived little impairment within 15-180 min after using kratom. In the in-person substudy, there were no significant changes in simulated driving performance after taking kratom. Using kratom before driving appears routine, however, self-reported and simulated driving findings suggest kratom effects at self-selected doses among regular kratom consumers do not produce significant changes in subjective and objective measures of driving impairment. Research is needed to objectively characterize kratom's impact on driving in regular and infrequent consumers. [ABSTRACT FROM AUTHOR]

Kratom is legally available in most states and is increasingly used. The authors of this commentary highlight kratom's unregulated status and other gaps that physicians should be aware of in light of emerging evidence on its clinical risks. [ABSTRACT FROM AUTHOR]

The article focuses on the dangers posed by unregulated psychotropic products like kratom, tianeptine, and phenibut, highlighting their availability in retail settings despite lacking FDA approval, which poses significant public health risks such as addiction and overdose. Topics include advocating for stricter regulation, enhancing public awareness, and promoting collaborative research efforts among healthcare organizations to address these hazards effectively.