Kratom Plant Research Articles

Examining the Impact of Cultivated Land Distance from Riparian Areas on the Growth and Quality of Red Kratom Alkaloids

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

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.

Research and publication gaps on kratom and kratom products: a scoping review of current literature.

Kratom plant, products derived from the plant, and plant phytochemicals are of great interest among researchers, clinicians, and consumers. However, there is a paucity of rigorously collected scientific data on their risk/safety profile and public health impact. This scoping review discusses original research articles published between 2022 and 2023. It focuses on identifying publication gaps on topics related to epidemiology, public health, and risk/safety profiles comparing evidence collected by researchers from Southeast Asia and the West. Our review of the Scopus database identified a total of 55 publications, including clinical case reports and case series reports, surveys, studies enrolling human participants, and publications based on large-scale national surveys or large-scale national or international health system database records. Overall, there is dearth of reliable data on key epidemiological factors, including the prevalence rates, and on objective and reliable indices of the risk/safety profiles. Rigorous and systematic studies including improved epidemiological surveillance, human laboratory, and controlled clinical studies are urgently needed to advance our understanding of public health consequences of consuming kratom and kratom-derived products and to improve our understanding of their risk/safety profile and additional analytical studies to better inform development of needed regulatory oversight.

The Antityrosinase Activity of Mitragyna speciosa Korth Leaf Ethanolic Extract

The kratom plant (Mitragyna speciosa Korth) is a the plant that is traditionally used to soften the skin. Kratom leaves have very strong antioxidant activity so they are predicted also to have anti-tyrosinase activity. The potential inhibition of tyrosinase enzyme activity is thought to come from the content of flavonoid compounds, polyphenols, steroids, tannins, and quinones. This research aims to determine the tyrosinase inhibitory activity of ethanol extract of M. speciosa leaves. The inhibitory activity of the tyrosinase enzyme using L-DOPA as substrate and kojic acid as positive control. Antityrosinase testing was carried out by in vitro method using UV-vis spectrophotometer through determination of IC50 value. The results of the antityrosinase activity test of ethanol extract of M. speciosa leaves showed an IC50 value of 2117.708 ppm. The ethanol extract of M. speciosa leaves is scientifically proven to have antityrosinase activity with a weak category.

The Dilemma of National Security Threats in Efforts to Realize the Banning of Kratom Plants by the National Anti-Narcotics Agency in Kapuas Hulu Regency

In this research, we will analyze various possible threat impacts from the non-optimal implementation of the 5-year transition program on the planned realization of the kratom plant ban policy in 2024 by The National Anti-Narcotics Agency (BNN) and related institutions in kratom plant cultivation areas, especially in the Kapuas Hulu Regency of West Kalimantan, which in fact is also the border area of the country. The obstruction of the implementation of the transition program in the realization plan for the kratom plant ban program in 2024 shows that the Indonesian government and related institutions are not serious in their efforts to protect kratom farmers and various other elements, which will then cause various polemics such as social problems, economic problems, environmental problems and transnational crimes, which are likely to lead to Indonesia's national security problems. The method used in this research is a qualitative research method, qualitative research is research that emphasizes more on observing phenomena and emphasizes more on the substance of meaning in these phenomena The analysis and sharpness of qualitative research is greatly influenced on the strength of words and sentences used in delivering research, the focus of qualitative research is on the process and the meaning of the results.

Insights into distinct signaling profiles of the µOR activated by diverse agonists.

Drugs targeting the μ-opioid receptor (μOR) are the most effective analgesics available but are also associated with fatal respiratory depression through a pathway that remains unclear. Here we investigated the mechanistic basis of action of lofentanil (LFT) and mitragynine pseudoindoxyl (MP), two μOR agonists with different safety profiles. LFT, one of the most lethal opioids, and MP, a kratom plant derivative with reduced respiratory depression in animal studies, exhibited markedly different efficacy profiles for G protein subtype activation and β-arrestin recruitment. Cryo-EM structures of μOR-Gi1 complex with MP (2.5 Å) and LFT (3.2 Å) revealed that the two ligands engage distinct subpockets, and molecular dynamics simulations showed additional differences in the binding site that promote distinct active-state conformations on the intracellular side of the receptor where G proteins and β-arrestins bind. These observations highlight how drugs engaging different parts of the μOR orthosteric pocket can lead to distinct signaling outcomes.

Legality of the Legal Status of Kratom Plants in Indonesia

This research aims to address the following research questions: Why is kratom plant considered illegal in Indonesia? Is there any legal protection for Indonesian farmers who cultivate kratom plants? This study employed normative legal method combining with a qualitative approach. This method relied on secondary data gathered from books, journals, laws, court decisions, and the internet. The information gathered was about kratom plants in Indonesia. In addition, a legal approach was also involved to review selected kratom plant regulation in Indonesia. The study revealed that the legality use of kratom is governed by the circular letter of the Head of the POM No: HK.04.4.42.421.09.16.1740 of 2016, the prohibition on the use of Mitragyna Speciosa (Kratom) in traditional medicines and health supplements. There are numerous side effects for those who consume the kratom plant, according to its content. Since 2013, it has been classified as an NPS (New Psychoactive Substance) and the National Narcotics Agency in an effort to prevent the spread of Kratom plants in Indonesia. Starting with the issuance of a policy, a total ban effective as of 2022. Farmers who cultivate Kratom Plants must switch crops because kratom is classified as Narcotics─ it cannot be cultivated or traded freely.

Probing the Activity of Mitragyna Speciosa (Kratom) Alkaloids at Serotonin G Protein‐Coupled Receptors

The nation’s persistent opioid epidemic requires innovative treatment interventions. Mitragyna speciosa, or kratom, is an alkaloid‐containing tropical plant that has emerged as a potential opioid substitute therapy in recent decades. There are, however, no FDA‐approved uses for kratom, and scientists are actively engaged to elucidate the potential therapeutic benefits and harmful effects of kratom. Studies of kratom alkaloids have mainly focused on their opioid receptor activity, but emerging data show kratom has physiologically‐relevant activity at other biological targets. We recently reported that two kratom alkaloids prevalent in leaves of the kratom plant, speciogynine and paynantheine, bind to serotonin (5‐HT) 5‐HT1ARs and 5‐HT2BRs with affinities (Ki) less ≤100 nM and that their 9‐O‐desmethyl metabolites are efficacious agonists at 5‐HT1ARs (León et al., 2021 PMID: 34467758). We are undertaking studies to evaluate the pharmacology of the most prevalent alkaloids found in kratom leaves at each of the genetically‐encoded 5‐HT G protein‐coupled receptors (GPCRs). To further elucidate 5‐HTR G‐protein transduction pathways modulated by kratom alkaloids, we are utilizing the TRUPATH biosensor platform. By evaluating the potency and efficacy of kratom alkaloids to modulate the activity of unique G alpha subtypes linked to 5‐HTRs, we will provide fundamental 5‐HTR pharmacological characteristics of kratom alkaloids. The 5‐HT2BR is a crucial target for drug safety profiling since activation of this receptor can lead to cardiac valvulopathy. In addition, we are testing kratom alkaloids with an appreciable 5‐HT2BR affinity for their potential mitogenic activity in HEK cells utilizing [3H]thymidine incorporation. This research will provide crucial information about kratom’s pharmacological profile, independent of opioid receptors, that may contribute to its physiological effects.

Plant growth and phytoactive alkaloid synthesis in kratom [Mitragyna speciosa (Korth.)] in response to varying radiance.

Leaves harvested from kratom [Mitragyna speciosa (Korth.)] have a history of use as a traditional ethnobotanical medicine to combat fatigue and improve work productivity in Southeast Asia. In recent years, increased interest in the application and use of kratom has emerged globally, including North America, for its potential application as an alternative source of medicine for pain management and opioid withdrawal syndrome mitigation. Although the chemistry and pharmacology of major kratom alkaloids, mitragynine and 7-hydroxymitragynine, are well documented, foundational information on the impact of plant production environment on growth and kratom alkaloids synthesis is unavailable. To directly address this need, kratom plant growth, leaf chlorophyll content, and alkaloid concentration were evaluated under three lighting conditions: field full sun (FLD-Sun), greenhouse unshaded (GH-Unshaded), and greenhouse shaded (GH-Shaded). Nine kratom alkaloids were quantified using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Greenhouse cultivation generally promoted kratom height and width extension by 93–114% and 53–57%, respectively, compared to FLD-Sun. Similarly, total leaf area and leaf number were increased by 118–160% and 54–80% under such conditions. Average leaf size of plants grown under GH-Shaded was 41 and 69% greater than GH-Unshaded and FLD-Sun, respectively; however, no differences were observed between GH-Unshaded and FLD-Sun treatments. At the termination of the study, total leaf chlorophyll a+b content of FLD-Sun was 17–23% less than those grown in the greenhouse. Total leaf dry mass was maximized when cultivated in the greenhouse and was 89–91% greater than in the field. Leaf content of four alkaloids to include speciociliatine, mitraphylline, corynantheidine, and isocorynantheidine were not significantly impacted by lighting conditions, whereas 7-hydroxymitragynine was below the lower limit of quantification across all treatments. However, mitragynine, paynantheine, and corynoxine concentration per leaf dry mass were increased by 40%, 35%, and 111%, respectively, when cultivated under GH-Shaded compared to FLD-Sun. Additionally, total alkaloid yield per plant was maximized and nearly tripled for several alkaloids when plants were cultivated under such conditions. Furthermore, rapid, non-destructive chlorophyll evaluation correlated well (r2 = 0.68) with extracted chlorophyll concentrations. Given these findings, production efforts where low-light conditions can be implemented are likely to maximize plant biomass and total leaf alkaloid production.

Physiological dependence to mitragynine indicated by a rapid cross-dependence procedure with heroin-dependent mice.

The potential of mitragynine to produce physiological dependence (withdrawal) was assessed using a rapid assessment procedure with male ICR mice exposed to heroin-admixed food followed by naloxone (subcutaneously, s.c.) precipitation of withdrawal. Initial studies indicated that 3 days of exposure to 3.0 mg/g of heroin-admixed food followed by naloxone (0.6 mg/kg) reliably precipitated withdrawal jumping and weight loss. Lower concentrations of heroin-admixed food and lower doses of naloxone produced fewer withdrawal signs. A longer exposure to heroin-admixed food did not produce significantly greater amounts of jumping or weight loss. Further, these withdrawal signs were dose-dependently reversed by s.c. administration of heroin immediately following naloxone administration. Mitragynine (s.c.) also dose-dependently suppressed naloxone-precipitated withdrawal signs. Additionally, both jumping and weight loss were suppressed over a comparable range of mitragynine doses when administered by gavage with a noticeably, but not significantly, higher potency than with s.c. administration. The ED50 values for mitragynine for the suppression of withdrawal by any route (354-911 μmol/kg) were greater than the minimally effective dose that decreased locomotor activity (251 μmol/kg) and from 40- to 104-fold greater than those for heroin. The results suggest inherent opioid dependence liability of mitragynine. The in vivo potency relations between mitragynine and heroin are consistent with a conclusion of dependence-producing effects, indicated by the suppression of withdrawal, comparable to standard opioid μ-receptor agonists, differing primarily in terms of potency. The present paper provides a method for the rapid assessment of physiological dependence liability applicable to other kratom plant constituents or any potential opioid dependence-producing agents.

Resilience State Security and the Role Sedative Agents in Military Pharmacy for State Defense in Future War

National defense is closely related to the role of an intelligence officer who is strong and capable of safeguarding the country's sovereignty. Intelligence covers many fields. One of those is medical intelligence. Mitragynine can be used as a sedative agent in a medical intelligence operation. To analyze a sedative agent in intelligent medical purposing of military aspect. This paper determines the role of Military Pharmacy in medical intelligence to support national defense using natural substances that contain a sedative agent. This research used narrative review method for this study obtained from Crossref, google scholar, PubMed, and Scopus range 2010 to 2021 in the English language, using the following terms: "National defense," "Medical intelligence," "Kratom" Mitragynine "Sedative agent" but we did not exclude out older works that were often cited and significant. Mitragynine binds to three types of receptors with varying affinities, with the highest affinity for μ, K, and δ-opioid receptors, which can be used as sedatives in medical intelligence to support national defense. Kratom is a plant endemic to Southeast Asia; this plant has a sedative effect at high doses. Kratom leaves contain thirty-seven alkaloid compounds. Both alkaloid compounds are Mitragynine and 7-hydroxymitragynine, both of which are included in the indole alkaloid compound, the main kratom compound. Plants that are used when facing the battlefield in maintaining national defense are very complex owned by the Indonesian state, that is the kratom plant which has a chance to strengthening people defense and security state facing of sixth generation war. This study needs to validate with more rigorous human clinical studies in the future.

Probability Induction of Kratom Plant Bioactive Components in Antidiabetic and Antiobesity Studies

Background: Kratom (Mitragyna speciosa Korth.) is widely used by the surrounding community as a traditional antidiabetic and antiobesity drug due to its high content of secondary metabolite compounds. The purpose of writing this review is to find out the bioinduction influence of Bacillus thuringiensis and Pseudomonas fluorescens and to find out the presence of an increase in secondary metabolites. Method: Writing and assessing source problems related to using literature study methods. Results: Kratom leaf methanol extract contains secondary metabolites of alkaloid groups, flavonoids, steroids/terpenoids, phenols and saponins. The main compound content of kratom leaves classified as alkaloids is mitragynine that has not been found in other plants. The administration of non-pathogenic bacteria such as Bacillus thuringiensis and Pseudomonas fluorescens can induce plant defenses and can accumulate the production of phenol compounds and flavonoids in plants. Conclusion: Based on the literature search results, kratom can indeed function as an antidiabetic and antiobesity and induction of microbes, namely Bacillus thuringiensis and Pseudomonas fluorescens bacteria can increase the content of secondary metabolites of plants. Through the increase in secondary metabolites, the efficacy of plants is higher to overcome health problems, namely antidiabetics and antiobesity.

Fraksinasi dan Identifikasi Ektrak Daun Mitragyna Speciosa Menggunakan Metode Kromatografi

Background: Mitragyna Speciosa or better known as Kratom is a typical plant from the Putusibau area, West Kalimantan. The most widely used part of this plant is the leaves. The kratom plant contains alkaloids, flavonoids, phenols, terpenoids-steroids, triterpenoids, saponins, and tannins. Alkaloid content is the most dominant and has benefits in this plant so it is necessary to do fractionation and identification of secondary metabolites. Objective: To fractionate and identify secondary metabolites from Mitragyna Speciosa leaf extract. Methods: The fractionation method was carried out using Column Chromatography while for identification using Thin Layer Chromatography. Results: 80 fractions were obtained from the column chromatography results, while the results of identification using thin layer chromatography showed that only the 2nd and 3rd fractions were obtained. The second fraction has two spots with Rf values of 0.51 and 0.73 and in the third fraction there are three spots with Rf values of 0.21; 0.52, and 0.74. Conclusion: Fractionation and identification by chromatographic method can be used as initial screening for secondary metabolite content in Mitragyna Speciosa leaf extract.

Anorectic Effect, Biochemical and Hematological Profiles of Alkaloid Extract from Mitragyna speciosa Korth. in Rats

There is an on-going debate about medicinal use of kratom plant (Mitragyna speciosa (MS)) on whether it has beneficial or adverse effects. This study aimed to examine long-term weight-reducing effects, toxicity, and dopamine pathway activation of MS alkaloid extract on adult male Wistar rats. In anorexic study, the rats were divided into 3 groups (n = 10), receiving intragastric administration once a day for 19 weeks as control (distilled water), chronic (20 mg/kg MS alkaloid extract) and withdrawal (20 mg/kg MS alkaloid extract for week 1-12 and distilled water for week 13-19) groups. Body weights were measured daily, and blood samples were collected at the end of study for biochemical and hematological tests. In immunohistochemistry, the effects of the extract (40 and 80 mg/kg) on the nucleus accumbens (NAc) and striatum (STr) were determined by using Fos-like immunoreactivity. From week 2 to 19, the results showed a significant reduction in body weight gain produced by the extract. Cessation of the treatment at week 12 did not result in a rebound weight gain. Chronic MS alkaloid extract treatment significantly decreased non-fasting blood sugar, triglyceride, uric acid and blood urea nitrogen (BUN). However, elevated SGOT may suggest possible hepatotoxicity. Chronic MSalkaloid extract treatment also produced baseline levels for most of the hematological parameters except a decrease of monocyte. In immunohistochemistry, the acute treatment did not induce Fos-like immunoreactivity in the NAc and STr.These data demonstrated the beneficial effects of the MS alkaloid extract for possible treatment of metabolic syndromes without toxicity and rewarding effect.

Refined Prediction of Pharmacokinetic Kratom-Drug Interactions: Time-Dependent Inhibition Considerations.

Preparations from the leaves of the kratom plant (Mitragyna speciosa) are consumed for their opioid-like effects. Several deaths have been associated with kratom used concomitantly with some drugs. Pharmacokinetic interactions are potential underlying mechanisms of these fatalities. Accumulating in vitro evidence has demonstrated select kratom alkaloids, including the abundant indole alkaloid mitragynine, as reversible inhibitors of several cytochromes P450 (CYPs). The objective of this work was to refine the mechanistic understanding of potential kratom-drug interactions by considering both reversible and time-dependent inhibition (TDI) of CYPs in the liver and intestine. Mitragynine was tested against CYP2C9 (diclofenac 4'-hydroxylation), CYP2D6 (dextromethorphan O-demethylation), and CYP3A (midazolam 1'-hydroxylation) activities in human liver microsomes (HLMs) and CYP3A activity in human intestinal microsomes (HIMs). Comparing the absence to presence of NADPH during preincubation of mitragynine with HLMs or HIMs, an ∼7-fold leftward shift in IC50 (∼20 to 3 μM) toward CYP3A resulted, prompting determination of TDI parameters (HLMs: K I , 4.1 ± 0.9 μM; k inact , 0.068 ± 0.01 min-1; HIMs: K I , 4.2 ± 2.5 μM; k inact , 0.079 ± 0.02 min-1). Mitragynine caused no leftward shift in IC50 toward CYP2C9 (∼40 μM) and CYP2D6 (∼1 μM) but was a strong competitive inhibitor of CYP2D6 (K i , 1.17 ± 0.07 μM). Using a recommended mechanistic static model, mitragynine (2-g kratom dose) was predicted to increase dextromethorphan and midazolam area under the plasma concentration-time curve by 1.06- and 5.69-fold, respectively. The predicted midazolam area under the plasma concentration-time curve ratio exceeded the recommended cutoff (1.25), which would have been missed if TDI was not considered. SIGNIFICANCE STATEMENT: Kratom, a botanical natural product increasingly consumed for its opioid-like effects, may precipitate potentially serious pharmacokinetic interactions with drugs. The abundant kratom indole alkaloid mitragynine was shown to be a time-dependent inhibitor of hepatic and intestinal cytochrome P450 3A activity. A mechanistic static model predicted mitragynine to increase systemic exposure to the probe drug substrate midazolam by 5.7-fold, necessitating further evaluation via dynamic models and clinical assessment to advance the understanding of consumer safety associated with kratom use.

Peralihan Sistem Mata Pencaharian dan Pola Interaksi Masyarakat Petani Kratom di Kecamatan Putussibau Utara, Kabupaten Kapuas Hulu, Kalimantan Barat

The people of North Putussibau are indigenous people with one of its prominent characteristics, namely the enactment of customs, procedures for interacting, in accordance with the customs and norms that the ancestors inherited. Based on the tradition and culture of the original community, the community carried out agricultural food crops and plantations in order to meet their daily needs. However, over time there has been a shift in the livelihoods of indigenous people to kratom plant farmers. This research was conducted to determine the factors that influence the change in the livelihood system of the North Putussibau community after the kratom market. This research was conducted in Banua Tengah Village, Sungai Uluk Palin Village, and Hilir Kantor Village, Putussibau Utara District, Kapuas Hulu Regency, Pontianak. The research location was chosen deliberately with the consideration that in the sample village there were indigenous people who had cultivated kratom for at least 2 years. Informants in this study were community leaders, village heads, kratom farmers, and village government. The data of this study were analyzed using an interactive model consisting of three activities that occurred simultaneously, namely: data reduction, data presentation, and drawing conclusions / verification. The results showed that there was a shift in the livelihood system where indigenous peoples were marked to begin to cultivate kratom along with previously existing cultivation plants. The transition to this livelihood system is influenced by three factors, namely: government policies, interactions with villagers, and norms or rules that affect indigenous people of North Putussibau in land use and resource extraction.

A validated method for the quantification of mitragynine in sixteen commercially available Kratom (Mitragyna speciosa) products

The recent rise in the recreational use of plant-based “legal highs” has prompted the development of methods for the identification of the bulk material, and quantification of their psychoactive components. One of these plants is Mitragyna speciosa, commonly referred to as Kratom. While traditional use of this plant was primarily for medicinal purposes, there has been a rise in its recreational use, and as a self-prescribed medication for opioid withdrawal. Although Kratom contains many alkaloids, mitragynine and 7-hydroxymitragynine are unique psychoactive biomarkers of the species, and are responsible for its psychoactive effects. A rapid validated method for the quantification of mitragynine in Kratom plant materials by direct analysis in real time-high-resolution mass spectrometry (DART-HRMS) is presented. It has a linear range of 5–100 μg mL−1, and a lower limit of quantification of 5 μg mL−1. The protocol was applied to determination of the mitragynine content of 16 commercially available Kratom plant products purchased online. The mitragynine amounts in these materials ranged from 2.76 to 20.05 mg g−1 of dried plant material. The utilization of DART-HRMS affords a mechanism not only for the preliminary identification of bulk plant material as being M. speciosa-derived (with no sample preparation required), but also provides the opportunity to quantify its psychoactive components using the same technique.