Kratom Research Articles

The regulatory effects of mitragynine on P-glycoprotein transporter.

Kratom preparation containing Mitragyna speciosa Korth plant is frequently used as a recreational drug. Mitragynine, a major alkaloid isolated from M. speciosa, is often detected concurrently with other drugs during forensic analysis, indicating a safety concern. P-glycoprotein (P-gp) is a multidrug transporter. Modulation of P-gp transport activity by drugs or herbal compounds in the brain may lead to drug-herb interactions, resulting in neurotoxicity. We aim to determine the effects of mitragynine on the P-gp regulation and possible neurotoxicity. The effects of mitragynine on the P-gp regulation were investigated in human brain capillary endothelial cells (hCMEC/D3) using molecular docking and dynamic simulation and an optimized bidirectional transport assay, respectively. Repeated-dose treatment and neurotoxicity assessment were carried out using a blood-brain barrier model and polimerase chain reaction (PCR) array. Mitragynine inhibits the P-gp transport activity via binding onto the nucleotide-binding domain site and forms a stable interaction with the P-gp protein complex. Nontoxic concentrations of mitragynine (<4 μM) and substrate drugs (0.001 μM) in the cells significantly enhanced endothelial cell permeability and elicited signs of neurotoxicity in PC-12 cells. Mitragynine is likely a P-gp inhibitor, hence concurrent administration of kratom products with P-gp substrates may lead to clinically significant interactions and neurotoxicity.

Aggression in a Cohort of Male Methamphetamine (METH) Users With and Without Kratom (Mitragyna speciosa Korth.) Use History in Malaysia

ABSTRACT 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.

Kratom (Mitragyna speciosa) use for self-management of pain: Insights from cross-sectional and ecological momentary assessment data

Kratom (Mitragyna speciosa) is increasingly used in the US for self-management of pain, despite limited research on its efficacy and safety. To better understand how and why people use kratom for pain self-management, we analyzed baseline survey data (N = 395) and 15-day ecological momentary assessment (EMA) data (N = 357) from kratom consumers across the US. Although we recruited participants based on their kratom use, not on whether they used it for pain management, nearly half (49.1 %) met criteria for chronic pain, with many reporting substantial pain relief and high effectiveness of kratom in managing pain. A majority (69.2 %) reported difficulties in obtaining adequate pain treatment, and most indicated that these challenges impacted their decision to try kratom. Most participants did not report concerns about overuse or significant side effects. EMA data showed that, regardless of chronic-pain status, pain relief was the most frequently endorsed primary motivation for daily kratom use. There were no significant association between daily pain levels and kratom use frequency, and no difference in the daily kratom use between those with vs. without chronic pain. Recent kratom use was associated with lower current pain levels. Stronger subjective effects of kratom were associated with lower pain levels. This effect was significantly moderated by chronic-pain status: those with chronic pain showed a stronger link between subjective kratom effects and pain reduction. These findings underscore the urgent need for systematic, rigorous research on long-term implications, efficacy, and safety of kratom in pain management to guide informed clinical practices and regulatory policies. PerspectiveThis study reveals that chronic pain is common among kratom consumers, who frequently use it for pain self-management and report significant relief, as shown by ecological momentary assessment. There is an urgent need for research into kratom's safety, efficacy, and mechanisms to guide clinical practice and inform policies.

Development and Validation of a Method for Detecting and Quantifying Mitragynine in Kratom Samples Using HPLC-PDA

Kratom (Mitragyna speciosa Korth) has been identified as a New Psychoactive Substance (NPS) by the United Nations Office on Drugs and Crime (UNODC) and included in the list of prohibited ingredients in food supplements and traditional medicine by Indonesian FDA. Therefore, a rapid, easy, and reliable analytical method is necessary to detect and quantify this plant and its products. This study developed a method for the detection and quantification of kratom products based on a unique compound, mitragynine, as a biomarker. A previous survey of determining mitragynine in Kratom using GC-MS, LC-MS/MS, UPLC, and HPLC-PDA. Previously, the HPLC-PDA method used a C8 column. Yet, for efficiency, it is also necessary to develop a test method using a C18 column. Analysis was performed using an HPLC - PDA system with Waters Atlantis T3-C18 (250 x 4.6 mm, 5 µm) column. The mobile phase comprises acetonitrile and formic acid 0.05%, pH 5.0 (75:25 v/v), delivered at a 1.0 mL/min flow rate. Detection was carried out at a wavelength of 225 nm. The analytical method was validated with test parameters of selectivity, system suitability, accuracy, precision, linearity, detection limit, and quantification limit. The validation study demonstrated an excellent linear concentration range of 1.96 - 6.01 µg/mL with a correlation coefficient of 0.9996; the detection limit is 0.14 µg/mL, while the limit of quantification is 0.45 µg/mL—accuracy method of 98.88 - 101.44% and a bias of 0.27%. The percent relative standard deviation for six independent assay determinations was 0.67%, and the intermediate precision was 1.56% on two days. The mitragynine amounts in these materials ranged from 6.01 to 6.31 mg/g of dried leaf material. Based on the research results, it can be concluded that the method developed provides quick, simple, reliable, accurate, and valid, and has an advantage over existing methods in terms of simplicity of sample preparation, short analysis time, and cost-effectiveness compared to GCMS and LCMS/MS and can be applied for future analysis in Kratom samples.

Binding characteristics of the major kratom alkaloid, mitragynine, towards serum albumin: Spectroscopic, calorimetric, microscopic, and computational investigations

Mitragynine (MTG) is a prominent indole alkaloid that is present abundantly in Mitragyna speciosa, commonly referred to as kratom. MTG has garnered significant attention due to its selective agonistic characteristics towards opioid receptors and related analgesic effects. In the circulatory system, the in vivo efficacy of MTG is dictated by its interaction with plasma proteins, primarily human serum albumin (HSA). In the present study, we utilized a broad methodology that included spectroscopic, calorimetric, microscopic, and in silico approaches to characterize the interaction between MTG and HSA. Alterations in the UV absorption spectrum of HSA by the presence of MTG demonstrated a ground-state complexation between the protein and the ligand. The Ka values obtained for the MTG–HSA interaction were in the range 103–104 M−1 based on analysis of fluorescence and ITC data, respectively, indicating an intermediate binding affinity. The binding reaction was thermodynamically favorable as revealed by ΔH, ΔS, and ΔG values of −16.42 kJ mol−1, 39.97 J mol−1 K−1, and −28.34 kJ mol−1, respectively. Furthermore, CD spectroscopy results suggested MTG binding induced minimal effects on the structural integrity of HSA, supported by computational methods. Changes in the dimensions of HSA particles due to aggregation, as observed using atomic force microscopy in the presence of MTG. Competitive drug displacement results seemingly suggested site III of HSA located at subdomain IB as the preferred binding site of MTG, but were in inconclusive. However, docking results showed the clear preference of MTG to bind to site III, facilitated by hydrophobic (alkyl and pi-alkyl) and van der Waals forces, together with carbon hydrogen bonds. Additionally, the MTG–HSA complexation was demonstrated to be stable based on molecular dynamics analysis. The outcomes of this study shed light on the therapeutic potential of MTG and can help in the design of more effective derivatives of the compound.

Drug-drug interactions of plant alkaloids derived from herbal medicines on the phase II UGT enzymes: an introductory review.

Herbal medicines are widely used as alternative or complementary therapies to treat and prevent chronic diseases. However, these can lead to drug-drug interactions (DDIs) that affect the glucuronidation reaction of UDP glucuronosyltransferases (UGTs), which convert drugs into metabolites. Plant extracts derived from medicinal herbs contain a diverse array of compounds categorized into different functional groups. While numerous studies have examined the inhibition of UGT enzymes by various herbal compounds, it remains unclear which group of compounds exerts the most significant impact on DDIs in the glucuronidation reaction. Recently, alkaloids derived from medicinal herbs, including kratom (Mitragyna speciosa), have gained attention due to their diverse pharmacological properties. This review primarily focuses on the DDIs of plant alkaloids from medicinal herbs, including kratom on the phase II UGT enzymes. Kratom is a new emerging herbal product in Western countries that is often used to self-treat chronic pain, opioid withdrawal, or as a replacement for prescription and non-prescription opioids. Kratom is well-known for its psychoactive alkaloids, which have a variety of psychopharmacological effects. However, the metabolism mechanism of kratom alkaloids, particularly on the phase II pathway, is still poorly understood. Simultaneously using kratom or other herbal products containing alkaloids with prescribed medicines may have an impact on the drug metabolism involving the phase II UGT enzymes. To ensure the safety and efficacy of treatments, gaining a better understanding of the DDIs when using herbal products with conventional medicine is crucial.

The potential of Mitragyna speciosa leaves as a natural source of antioxidants for disease prevention.

Mitragyna speciosa is famous for its addictive effect. On the other hand, this plant has good potential as an antioxidant agent, and so far, it was not explicitly explained what the most contributing compound in the leaves to that activity is. This study has been conducted using several computational methods to determine which compounds are the most active in interacting with cytochrome P450, myeloperoxidase, and NADPH oxidase proteins. First, virtual screening was carried out based on molecular docking, followed by profiling the properties of adsorption, distribution, metabolism, excretion, and toxicity (ADMET); the second one is the molecular dynamics (MD) simulations for 100 ns. The virtual screening results showed that three compounds acted as inhibitors for each protein: (-)-epicatechin, sitogluside, and corynoxeine. The ADMET profiles of the three compounds exhibit good drug ability and toxicity. The trajectories study from MD simulations predicts that the complexes of these three compounds with their respective target proteins are stable. Furthermore, these compounds identified in this computational study can be a potential guide for future experiments aimed at assessing the antioxidant properties through in vitro testing.

An in vitro evaluation on metabolism of mitragynine to 9-O-demethylmitragynine

Kratom (Mitragyna Speciosa Korth.) is an indigenous tree native to Southeast Asia whose leaves have been traditionally ingested as a tea and has seen its popularity increase in the United States. Although kratom and its constituents presently have no approved uses by the Food and Drug Administration, its major alkaloids (e.g., mitragynine) have psychoactive properties that may hold promise for the treatment of opioid cessation, pain management, and other indications. 9-O-demethylmitragynine is a major metabolite formed from mitragynine metabolism (36 % total metabolism) and displays similar pharmacologic activity. Cytochrome P450 (CYP) 3A4 has been identified as a major enzyme involved in mitragynine metabolism; however, the in vitro metabolism parameters of 9-O-demethylmitragynine formation are not well defined and a risk of potential drug interactions exists. Using human liver S9 fractions, 9-O-demethylmitragynine formation was generally linear for enzyme concentrations of 0–0.25 mg/mL and incubation times of 5–20 min. 9-O-demethylmitragynine displayed a Km 1.37 μM and Vmax of 0.0931 nmol/min/mg protein. Known CYP inhibitors and compounds that might be concomitantly used with kratom were assessed for inhibition of 9-O-demethylmitragynine formation. Ketoconazole, a CYP3A index inhibitor, demonstrated a significant effect on 9-O-demethylmitragynine formation, further implicating CYP3A4 as a major metabolic pathway. Major cannabinoids (10 μg/mL) displayed minor inhibition of 9-O-demethylmitragynine formation, while all other compounds had minimal effects. Mixtures of physiological achievable cannabinoid concentrations also displayed minor effects on 9-O-demethylmitragynine formation, making a metabolic drug interaction unlikely; however, further in vitro, in vivo, and clinical studies are necessary to fully exclude any risk.

Mitragynine and morphine produce dose-dependent bimodal action on food but not water intake in rats.

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.

Introducing Noble Gas as Space Holder under High Pressure to Design Porous Titanium Carbides with Open Metal Sites for Hydrogen Storage at Near-Ambient Conditions.

It has been a long-standing challenge to develop high-performance solid-state hydrogen storage materials operated under near-ambient conditions. In this work, we propose a new strategy of using noble gases for space holding to design porous titanium carbides with abundant open metal sites for hydrogen storage. By using machine learning and graph theory-assisted universal structure searching methods, we obtain 28 porous titanium carbides from three precursors (TiC dimer, C atom, and Kr atom) under 30 GPa of pressure. The stability and hydrogen storage performance of the resulting structures are further assessed and validated through density function theory and grand canonical Monte Carlo simulations with a DFT-fitted force field. Finally, p-TiC2 is identified as a promising quasi-molecular hydrogen storage material with capacity of 4.0 wt % and 106.0 g/L at 230 K and 16 bar.

Rapid mitragynine quantification and fingerprinting of products from Mitragyna speciosa Korth. leaf (Kratom) using high-performance thin-layer chromatography.

Kratom (leaves from Mitragyna speciosa Korth.; Rubiaceae) is a herbal medicine known for its analgesic properties and psychoactive effects. Kratom in Thailand is currently legal; however, it is prohibited in some countries and considered a narcotic plant. Our aim was to establish a reliable, simple, and rapid method for quantifying mitragynine in Kratom leaves and related products through a combination of high-performance thin-layer chromatography (HPTLC) and densitometry. A densitometric HPTLC method was developed and validated in terms of specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, and robustness. The fingerprints of kratom leaves, Mitragyna spp., and related products were constructed. For HPTLC, samples were applied to silica gel 60 F254 plates, and the mobile phase comprised n-hexane, ethyl acetate, and triethylamine (1:1:0.15, v/v/v). Densitometric detection was carried out under ultraviolet light at a wavelength of 226 nm. The validated method exhibited a range of 14.31-143.10 μg/mL, yielding a correlation coefficient of 0.9993. Spiked recovery rates were within a range of 98.3%-100.9%, and the LOD and LOQ were 3.80 and 11.53 μg/mL, respectively. Kratom samples were analyzed with the developed method, and the correlation coefficient was 0.9641, compared to the high-performance liquid chromatography-diode-array detection (HPLC-DAD) method. The HPTLC fingerprints displayed a distinctive pattern, facilitating discrimination among different plant parts and Mitragyna spp. The established method offers the advantages of simplicity, ease of use, and speed of analysis, serving as a practical alternative for mitragynine quantification in kratom leaf and its related products.

Quantitative analysis of selected alkaloids of Mitragyna speciosa using 1H quantitative nuclear magnetic resonance spectroscopy.

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.

Comparative Analysis of Mitragynine Content in Kratom Leaves (Mitragyna speciosa Korth) from Kabupaten Kapuas Hulu Using HPLC Method

Opioid drugs are common analgesics for managing chronic pain, but they have significant short- and long-term side effects. Despite this, opioid consumption continues to rise in high-income countries, raising concerns about dependency. Kratom (Mitragyna speciosa Korth), which has opioid-like effects, shows potential as an analgesic with fewer side effects. This study aimed to explore and compare the mitragynine content in Kratom leaves from various regions in Kabupaten Kapuas Hulu, Indonesia, using High-Performance Liquid Chromatography (HPLC). Kratom leaves from 14 regions in Kapuas Hulu were collected, dried, and ground. Mitragynine was extracted using 70% ethanol and analyzed with HPLC. The yield percentage and mitragynine content in both the powdered simplisia and ethanol extract were measured and compared. The study showed that the average ethanol extract yield was 28%, with the highest yield from Elis Menendang (31.20%) and the lowest from Nanga Lauk (23.86%). Mitragynine content was significantly higher in the ethanol extract (3.22%) compared to the powdered simplisia (1.46%). Samples from Lanjak, Jongkong, Bunut, and Putussibau Kota showed mitragynine content exceeding 4% in the ethanol extract. HPLC analysis indicated that ethanol extraction significantly increases the mitragynine content in Kratom leaves compared to powdered simplisia, up to twice as much.

Antibacterial activity of Mitragyna speciosa Korth. leaves

Antibacterial activity of Mitragyna speciosa Korth. leaves

The Mitragyna speciosa (kratom) alkaloid mitragynine: Analysis of adrenergic α2 receptor activity in vitro and in vivo

Mitragynine, an alkaloid present in the leaves of Mitragyna speciosa (kratom), has a complex pharmacology that includes low efficacy agonism at μ-opioid receptors (MORs). This study examined the activity of mitragynine at adrenergic α2 receptors (Aα2Rs) in vitro and in vivo. Mitragynine displaced a radiolabeled Aα2R antagonist ([3H]RX821002) from human Aα2ARs in vitro with lower affinity (Ki = 1260 nM) than the agonists (−)-epinephrine (Ki = 263 nM) or lofexidine (Ki = 7.42 nM). Mitragynine did not significantly stimulate [35S]GTPγS binding at Aα2ARs in vitro, but in rats trained to discriminate 32 mg/kg mitragynine from vehicle (intraperitoneally administered; i.p.), mitragynine exerted an Aα2R agonist-like effect. Both α2R antagonists (atipamezole and yohimbine) and MOR antagonists (naloxone and naltrexone) produced rightward shifts in mitragynine discrimination dose-effect function and Aα2R agonists lofexidine and clonidine produced leftward shifts. In the mitragynine trained rats, Aα2R agonists also produced leftward shifts in discrimination dose-effect functions for morphine and fentanyl. In a separate rat cohort trained to discriminate 3.2 mg/kg i.p. morphine from vehicle, naltrexone produced a rightward shift, but neither an Aα2R agonist or antagonist affected morphine discrimination. In a hypothermia assay, both lofexidine and clonidine produced marked effects antagonized by yohimbine. Mitragynine did not produce hypothermia. Together, these data demonstrate that mitragynine acts in vivo like an Aα2R agonist, although its failure to induce hypothermia or stimulate [35S]GTPγS binding in vitro, suggests that mitragynine maybe a low efficacy Aα2R agonist.

Antioxidant and antibacterial efficiency of the ethanolic leaf extract of Kratom (Mitragyna speciosa (Korth.) Havil) and its effects on growth, health, and disease resistance against Edwardsiella tarda infection in Nile tilapia (Oreochromis niloticus)

The research examined the impact of an ethanolic extract from the leaves of Kratom (Mitragyna speciosa (Korth.) Havil.) on the growth, antioxidant capacity, immune-related gene expression, and resistance to disease caused by Edwardsiella tarda in Nile tilapia (Oreochromis niloticus). The findings revealed that the extract had the important phytochemical content in the extract included total phenolics content, total flavonoids content, vitamin C, and total antioxidant capacity and 5.42 % of the crude extract was mitragynine. The extract demonstrated antioxidant activity, as evidenced by its IC50 values against ABTS and DPPH radicals and its ferric reducing power in vitro. Moreover, the MIC-IC50 value of 0.625 mg/mL indicated that the growth of the bacteria was reduced by approximately 50 %, and the MBC was 2.50 mg/mL against E. tarda. Furthermore, the orally administered Kratom leaf extract to fingerling tilapia for 8 weeks exhibited a noticeable increase in oxidative stress, as demonstrated by the increase in MDA production in the 10 and 25 g/kg groups. It also exhibited an increase in acetylcholinesterase (AChE) activity in muscle tissue at the 50 g/kg group. However, when administered at a feeding rate of 5–10 g/kg feed, the extract showed an increase in the expression of immune-related genes (IL1, IL6, IL8, NF-kB, IFNγ, TNFα, Mx, CC-chemokine, CD4, TCRβ, MHC-IIβ, IgM, IgT, IgD) and enhanced resistance to E. tarda infection in fish. Conversely, administering the extract at 25–50 g/kg feed resulted in contrasting effects, suppressing and reducing the observed parameters. Nevertheless, feeding the extract at all concentrations for 8 weeks did not produce any changes in the histology or systemic functioning of the liver and intestines, as indicated by blood biochemistry. These findings suggest that the ethanolic leaf extract from Kratom has the potential to be used as a substitute for antibiotics in the management of bacterial infections in Nile tilapia culture, with a recommended dosage of 5–10 g/kg feed/day for a maximum of 8 weeks.

Using rDNA ITS2 barcoding to identify kratom (Mitragyna speciosa) from the genus Mitragyna and Neolamarckia cadamba.

This study collected 80 samples of suspected kratom plant powder. A polymerase chain reaction sequence analysis was conducted using two sets of DNA barcode primers for plant ribosomal (r)DNA internal transcribed spacers (ITSs), namely, ITS3/ITS4 and ITS-p3/ITS-u4. Among the 80 samples, 40 were analyzed using the ITS3/ITS4 primer pair, and then DNA sequences were subjected to a National Center for Biotechnology Information-Basic Local Alignment Search Tool (NCBI-BLAST) comparison. Results showed that 29 samples had a 100% match (364/364) with Mitragyna speciosa (kratom), and 6 samples had a 99.73% match (363/364) with M. speciosa, whereas 5 samples had disordered and unreadable sequences. The 5 unreadable samples and an additional 40 suspected kratom samples were then analyzed using the ITS-p3/ITS-u4 primer pair, followed by an NCBI-BLAST comparison. Among these, 32 samples had a 100% match (404/404) with M. speciosa, and 11 samples had a 99.75% match (403/404) with M. speciosa. Among the samples with sequences matching M. speciosa, three distinct types were observed (no variance/404, 287M/404, and 287A/404). One sample had a 99.51% match (404/406) with Neolamarckia cadamba, and another sample had a sequencing length of 305bp, with 25 positions showing mixed base pairs, indicating a mixture of different species. Analysis of the mixed base pair pattern suggested a possible mixture of M. speciosa and N. cadamba. Actually, M. speciosa and N. cadamba have very similar external morphologies. This indicates that the ITS-p3/ITS-u4 primer pair is effective in distinguishing mixtures of M. speciosa and N. cadamba and is thus more suitable than ITS3/ITS4 for identifying and analyzing samples of suspected kratom plant powder.

In-vitro hepatotoxic activity of mitragynine and paynantheine isolated from the leaves of Mitragyna speciosa Korth. (Kratom)

Mitragynine, a primary alkaloid found in kratom leaves has been reported to have a broad range of pharmacological and toxicological properties while its congener, paynatheine has comparatively less information available on these aspects. Mitragynine and its congener, paynantheine, were isolated from the ethanol kratom leaves extract using gravity column chromatography techniques. Our study evaluated the cytotoxicity potential of mitragynine and paynantheine on normal human liver cell line, HL-7702, and human hepatoma cell line, HepG2. Mitragynine exhibited a moderate inhibitory effect on the HepG2 cell line with IC50 value of 42.11 ± 1.31 μM in comparison with vinblastine (IC50: 15.45 ± 0.72 μM) while it showed non-cytotoxic properties towards the HL-7702 cell line with concentrations ranging below 200 μM. In contrast, paynantheine exhibited weak cytotoxic properties towards HepG2 and HL-7702 cell lines. Further comprehensive evaluations of both compounds are needed to establish more details on the cytotoxicity potential of kratom alkaloids.

The effects of Mitragyna speciosa extracts on intestinal microbiota and their metabolites in vitro fecal fermentation.

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. 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%). 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.

Growing pains with kratom: experiences discussed in subreddits contrast with satisfaction expressed in surveys.

"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. 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. 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. 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.