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.

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.

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.

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

INTRODUCTION: 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. OBJECTIVE: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSION: 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.

Ventricular fibrillation during football training as a consequence of kratom and caffeine use in an adolescent: case report.

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.

Controversies in Assessment, Diagnosis, and Treatment of Kratom Use Disorder.

PURPOSE OF REVIEW: We apply the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) criteria for substance use disorders (SUDs) to the herbal product kratom. Similarities and differences between kratom use disorder (KUD) and other SUDs are explored, along with assessment, diagnostic, and therapeutic recommendations for KUD. RECENT FINDINGS: Literature reports of "kratom addiction" or KUD rarely specify the criteria by which patients were diagnosed. Individuals meeting DSM-5 KUD criteria typically do so via tolerance and withdrawal, using more than intended, and craving, not functional or ​psychosocial disruption, which occur rarely. Most clinicians who use medication to treat patients with isolated KUD select buprenorphine formulations, although there are no controlled studies showing that buprenorphine is safe or efficacious in this patient population. Diagnosis and treatment decisions for KUD should be systematic. We propose an algorithm that takes into consideration whether KUD occurs with comorbid opioid use disorder.

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, TCRß, MHC-IIß, 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.

Characterization of kratom use and knowledge at a rural, Oregon community health center.

BACKGROUND: Kratom is an herbal supplement that has drawn attention for its use in the self-treatment of opioid withdrawal, and its widespread availability with minimal restrictions. Past web-based research has attempted to determine patterns and trends of use, but generalizability to underserved populations is unclear. OBJECTIVE: The purpose of this study was to characterize behavior related to kratom, attitudes toward kratom, and knowledge of kratom in a rural, underserved population. METHODS: We developed, refined, and administered a cross-sectional, 36-item survey to examine use, attitudes, and knowledge of kratom. We recruited participants and administered the survey alongside medical office appointments between January and April 2023. Data were summarized using descriptive statistics. RESULTS: A convenient sample of 186 patients (of the 907-patient clinic panel) were invited to participate and 150 returned the survey. A majority of patients were female (52.0%) and White (86.6%), and about half had an income below the federal poverty level (48.5%). Seventeen participants reported prior experience with kratom use, with one actively using kratom. The most commonly reported reasons for use were pain (47.1%) and mental health (41.2%). Kratom knowledge was low regardless of kratom use history, with the majority of respondents correctly answering between 1 and 3 questions (n = 71 of 86; 82.3%) of the 5 knowledge-focused items. CONCLUSION: Results suggest that while active kratom use is uncommon in this Oregon population, one in ten surveyed had used kratom. Regardless of past use, respondents had limited knowledge of kratom. Future research should focus on understanding trends in kratom use behaviors in underserved populations, addressing patient knowledge gaps, and evaluating patient safety and health equity implications.

Endogenous Opioid Activity as the Mechanism of Action for Mitragyna speciosa (Kratom): The Current State of the Evidence.

Kratom (Mitragyna speciosa) is a substance derived from botanical compounds native to Southeast Asia. This substance has been cultivated predominantly in Thailand, Malaysia, Vietnam, and Myanmar, where it has historically been used in traditional medicine as a near panacea for several health problems. Such ritualistic use of kratom has been present for centuries; however, recreational use appears to have increased globally, especially in the United States. Pharmacodynamic and pharmacokinetic studies have found that kratom demonstrates a unique parabolic, dose-dependent pattern of effects ranging from stimulation to opioid and analgesic effects. Pharmacological research indicates that kratom is both a mu opioid receptor (µ-OR; MOR) and a kappa opioid receptor (κ-OR; KOR) agonist, which mediates its analgesic effects. Other research suggests that kratom may simultaneously act on dopaminergic and serotonergic receptors, which mediate its stimulant effects. This chapter reviews the literature related to the structural, functional, and cultural characteristics of kratom use. We begin with an overview of current and historical patterns of kratom, followed by a review of data on the pharmacodynamics and pharmacokinetics of kratom thus far.

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

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.

A review on Mitragyna speciosa (Rubiaceae) as a prominent medicinal plant based on ethnobotany, phytochemistry and pharmacological activities.

Mitragyna speciosa Korth (kratom) is a tropical indigenous tree of Southeast Asia. It is commonly consumed by the people due to its various pharmacological properties. The leaves of this plant are traditionally used for the treatment of several diseases including pain, fever, cough, anxiety, depression, obesity, diarrhoea, wound healing, diabetes, hypertension as well as for the prevention of cancer and improvement of sexual performance. Phytochemical investigations have confirmed the presence of more than forty alkaloids along with the presence of other bioactive secondary metabolites. Among the alkaloids isolated, mitragynine and 7-hydroxymitragynine along with their derivatives have been widely evaluated and reported to possess various pharmacological effects. Hence, the aim of this review is to shed light on the traditional uses of kratom and the scientific studies to justify the folkloric claims and active principles responsible for the various medicinal effects associated with the leaves of this plant. This review highlights the potential benefits and toxicities associated with M. speciosa leaves along with the phytochemistry. Moreover, the existing gaps in the field of M. speciosa study have been identified along with the future directions to further avail the benefits of this plant species.

Kratom as a potential substance use disorder harm reduction agent.

Substance use disorders contribute to considerable U.S. morbidity and mortality. While effective pharmacotherapy options are available to treat opioid and alcohol use disorders, for a variety of reasons, many patients lack access to treatment or may be reluctant to seek care due to concerns such as perceived stigma or a current lack of desire to completely curtail their substance use. Furthermore, treatment options are limited for patients with stimulant or polysubstance use disorders. Thus, there is considerable need to expand the substance use disorder harm reduction armamentarium. Kratom (Mitragyna speciosa Korth.) is an herbal substance that can produce both opioid and stimulant-like effects, and its use in the US is growing. Though there are concerns regarding adverse effects, dependence risk, and limited regulation of its manufacturing and sale, the pharmacology of kratom and early preclinical studies suggest a potential role as a harm reduction agent for various substance use disorders, and it has historically been used in Southeast Asia for such purposes. The goal of this review is to describe kratom's history of use, pharmacology, and early pre-clinical and observational research regarding its therapeutic potential in opioid use disorder, as well as alcohol, stimulant, and polysubstance use disorders, while also highlighting current concerns around its use, existing gaps in the literature, and directions for future research.

Kratom (Mitragyna speciosa) Use and Mental Health: A Systematic Review and Multilevel Meta-Analysis.

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 (ß1 = -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.

Sequence variation of commercially available kratom products at universal DNA barcode regions.

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.

An In Vitro Examination of Whether Kratom Extracts Enhance the Cytotoxicity of Low-Dose Doxorubicin against A549 Human Lung Cancer Cells.

Doxorubicin is an effective chemotherapeutic agent in the treatment of solid hematological and non-hematological carcinoma. However, its long-term usage could result in side effects, such as cardiomyopathy, chronic heart failure, neurotoxicity and cancer cell resistance. In this study, we reported the sensitivity enhancement of A549 human lung cancer cells on doxorubicin at a low dose (0.1 ppm) in combination with 10-60 ppm of crude and alkaloid extracts derived from the leaves of Kratom (Mitragyna speciosa (Korth.) Havil. Rubiaceae). A549 cancer cell lines were insensitive to the crude extract containing low mitragynine (MG) (4-5%), while these cells were moderately inhibited by the alkaloid extract containing 40-45% MG (IC50 of 48-55 ppm). The alkaloid extract was found to inhibit A549 cancer cells via apoptosis as suggested by the higher relative fluorescence intensity with Annexin compared to that in propidium iodide (PI), i.e., a positive Annexin and a negative PI. The combination of crude extract and doxorubicin sensitized A549 cancer cells to doxorubicin by 1.3 to 2.4 times, while the combination with the alkaloid induced a 2.6- to 3.4-fold increase in sensitivity. The calculated combination index (CI) for doxorubicin with the crude and alkaloid extracts was 0.6 and 0.3, respectively, showing potential synergistic combinations to reduce the level of dosage of doxorubicin used in chemotherapy. In addition, the synergistic enhancement effect of crude extract on the cytotoxic activity of doxorubicin provides insights into the plausibility of non-alkaloids to influence the biological activities of Kratom.

Paynantheine more effectively reverses multidrug resistance in malignant EPG85.257RDB and MCF7MX cells than morphine and speciociliatine.

The possible interactions of morphine, paynantheine and speciociliatine alkaloids with ATP-binding cassette (ABC) transporters was investigated. The compounds were docked against ABCG2 and ABCB1 to predict the binding mode of alkaloids in active binding sites. The cytotoxicity of morphine, paynantheine and speciociliatine for EPG85.257RDB and MCF7MX cells was determined and ABCB1 and ABCG2 gene and protein expression were determined. The binding score of paynantheine to ABCB1 was higher in the docking studies. Paynantheine and speciociliatine had similar binding scores to ABCB1, but higher binding scores to ABCG2 than did morphine. Paynantheine and speciociliatine were more effective against MCF7MX and EPG85.257RDB cells and showed greater cyctotoxicity in the MTT assay. The effect of morphine and paynantheine on the ABCB1 gene and protein expression suggests these compounds can reduce resistance in cancer patients, but that speciociliatine may not be a suitable candidate because of its increased ABCB1 expression while speciociliatine decreased the expression of ABCG2 in MCF7MX cells. This indicates that speciociliatine is a better candidate for reducing drug resistance in this cell line. Structural modification, drug-metabolizing enzymes and differences in the binding sites could cause functional differences between these compounds.

An insight review on the neuropharmacological effects, mechanisms of action, pharmacokinetics and toxicity of mitragynine.

Mitragynine is one of the main psychoactive alkaloids in Mitragyna speciosa Korth. (kratom). It has opium-like effects by acting on µ-, δ-, and κ-opioid receptors in the brain. The compound also interacts with other receptors, such as adrenergic and serotonergic receptors and neuronal Ca2+ channels in the central nervous system to have its neuropharmacological effects. Mitragynine has the potential to treat diseases related to neurodegeneration such as Alzheimer's disease and Parkinson's disease, as its modulation on the opioid receptors has been reported extensively. This review aimed to provide an up-to-date and critical overview on the neuropharmacological effects, mechanisms of action, pharmacokinetics and safety of mitragynine as a prospective psychotropic agent. Its multiple neuropharmacological effects on the brain include antinociceptive, anti-inflammatory, antidepressant, sedative, stimulant, cognitive, and anxiolytic activities. The potential of mitragynine to manage opioid withdrawal symptoms related to opioid dependence, its pharmacokinetics and toxic effects were also discussed. The interaction of mitragynine with various receptors in the brain produce diverse neuropharmacological effects, which have beneficial properties in neurological disorders. However, further studies need to be carried out on mitragynine to uncover its complex mechanisms of action, pharmacokinetics, pharmacodynamic profiles, addictive potential, and safe dosage to prevent harmful side effects.

An update on the clinical pharmacology of kratom: uses, abuse potential, and future considerations.

INTRODUCTION: Kratom (Mitragyna speciosa) has generated substantial clinical and scientific interest as a complex natural product. Its predominant alkaloid mitragynine and several stereoisomers have been studied for activity in opioid, adrenergic, and serotonin receptors. While awaiting clinical trial results, the pre-clinical evidence suggests a range of potential therapeutic applications for kratom with careful consideration of potential adverse effects. AREAS COVERED: The focus of this review is on the pharmacology, pharmacokinetics, and potential drug-drug interactions of kratom and its individual alkaloids. A discussion on the clinical pharmacology and toxicology of kratom is followed by a summary of user surveys and the evolving concepts of tolerance, dependence, and withdrawal associated with kratom use disorder. EXPERT OPINION: With the increasing use of kratom in clinical practice, clinicians should be aware of the potential benefits and adverse effects associated with kratom. While many patients may benefit from kratom use with few or no 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.

Microencapsulation of Mitragyna leaf extracts to be used as a bioactive compound source to enhance in vitro fermentation characteristics and microbial dynamics.

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