No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Abstract
In early 2010, the Thai Office of the Narcotics Control Board (ONCB) developed a policy proposal to review different aspects of the criminal justice process in relation to drug cases. The possibility of decriminalising the indigenous psychoactive plant, kratom, was included in the ONCB’s proposal for consideration by the Ministry of Justice. This briefing paper provides an overview of issues related to kratom legislation and policy in Thailand as well as a set of conclusions and recommendations to contribute to a reassessment of the current ban on kratom in Thailand and the region. The briefing is based on desk research of existing documentation as well as field research carried out in October and November 2010 in Bangkok, Surat Thani, Trang, Satun, Songkhla, and Hat Yai in Thailand.
... Kratom (Mitragyna speciosa Korth., Rubiaceae; also known as ketum) is made from the leaves of a tropical tree in the coffee family indigenous to Southeast (SE) Asia, where it has been used for centuries as medicine for various ailments, including hypertension, diarrhea, cough, and fever (Tanguay, 2011;Cinosi et al., 2015;Singh et al., 2016). Despite such traditional medicinal use, it is important to recognize that neither kratom, nor its constituents (e.g., "alkaloids"), nor metabolites have been approved as safe and effective medicines for any therapeutic use. ...
... Nonetheless, widespread use for health and well-being include diverse uses reported by consumers as reasons for their use. For example, at low doses, kratom has long been consumed orally as a stimulant to enhance stamina and productivity, making it particularly popular among field laborers working long days in arduous conditions (Tanguay, 2011;Prozialeck et al., 2012;Hassan et al., 2013;Warner et al., 2016). Consumption remains widespread in kratom's native lands, where people commonly chew raw kratom leaves or boil leaves to make tea . ...
... A longstanding use for kratom in SE Asia is to increase productivity. In a survey of over a million kratom users in this region, a primary motive was to enhance physical performance (Tanguay, 2011). This may explain why a preponderance of traditional consumers are male agricultural laborers. ...
Kratom (Mitragyna speciosa Korth., Rubiaceae) is a plant native to Southeast Asia, where it has been used for centuries as a mild stimulant and as medicine for various ailments. More recently, as kratom has gained popularity in the West, United States federal agencies have raised concerns over its safety leading to criminalization in some states and cities. Some of these safety concerns have echoed across media and broad-based health websites and, in the absence of clinical trials to test kratom’s efficacy and safety, considerable confusion has arisen among healthcare providers. There is, however, a growing literature of peer-reviewed science that can inform healthcare providers so that they are better equipped to discuss kratom use with consumers and people considering kratom use within the context of their overall health and safety, while recognizing that neither kratom nor any of its constituent substances or metabolites have been approved as safe and effective for any disease. An especially important gap in safety-related science is the use of kratom in combination with physiologically active substances and medicines. With these caveats in mind we provide a comprehensive overview of the available science on kratom that has the potential to i clarity for healthcare providers and patients. We conclude by making recommendations for best practices in working with people who use kratom.
... The leaves have been applied directly to wounds as a local anesthetic, and antihelminth. The leaves extracts are used to treat coughs, colds, diarrhea, diabetes, hypertension, malaria, general weakness, musculoskeletal pain, and opium substitute, as well as to increase stamina and sexual prowess (Suwanlert, 1975;Chua and Schmelzer, 2001;Assanangkornchai et al., 2007;Tanguay, 2011;Ahmad & Aziz, 2012;Neng et al., 2015;Papsun et al., 2019;Singh et al., 2019a). Due to its stimulant effect, Kratom is often consumed by local laborers to increase the work rate and reduce fatigue (Cinosi et al., 2015). ...
... In Indonesia, Kratom is legally cultivated and exported on large scale to Asia, North America, and Europe. However, in 2008 it was banned for use in processed food and later in 2016 restricted for sale as traditional medicine and expected to be deemed illegal in 2022 by Indonesia FDA (Tanguay, 2011;Hassan et al., 2013;Badan Pengawas Obat dan Makanan, 2016;Rokib, 2019;Andilala, 2019). However, in February 2020 Indonesia's Ministry of Agriculture enlisted Kratom under medicinal plants classification, making its legal status in limbo (Menteri Pertanian Republik Indonesia, 2020). ...
p>Kratom ( Mitragyna speciosa (Korth.) Havil.) is a plant that originated from the rainforest in Southeast Asia, mainly grows in Thailand, Malaysia, and Indonesia. Kratom has been used traditionally as an herbal remedy for the treatment of various illnesses. Kratom gained notoriety due to its potential as an analgesic, opiate withdrawal treatment, anxiolytic, antidepressant, and antidiabetic with an unclear risk of addiction and toxicity fueled by a false sense of security due to its identity as a member of the coffee family. This article is a narrative review on kratom to highlight its pharmacological and toxicological properties, and the analytical method of Kratom, especially its potential as an opioid withdrawal therapy and its risk of abuse.</p
... Of specific to Thai adolescents was the high probability of kratom or kratom cocktail use among this group as this drug is highly available in Thailand and perceived as a "soft drug" with little or no harmful effect. The kratom cocktail (dubbed "4 × 100", or "4 times 100") is a mixture of four ingredients, namely boiled kratom leaves, soft drink such as coca cola, cough syrup, and either coffee or codeine, and is usually chilled with ice [35][36][37]. It is common among teenagers who drink together in a group or with friends [36,37]. ...
... The kratom cocktail (dubbed "4 × 100", or "4 times 100") is a mixture of four ingredients, namely boiled kratom leaves, soft drink such as coca cola, cough syrup, and either coffee or codeine, and is usually chilled with ice [35][36][37]. It is common among teenagers who drink together in a group or with friends [36,37]. This issue requires urgent action across multiple sectors, including health, education and social services for screening and early intervention of these high-risk students. ...
Background
Alcohol and drug use and other health-risk behaviors tend to cluster together among adolescents and contribute a large amount of harm to both themselves and to others. This paper aims to characterize secondary school students based on their clusters of health-risk behaviors and identify factors determining class membership to these behavior-clusters.
Methods
Data from a national school survey was used to identify clusters of alcohol and drug use and other health-risk behaviors among secondary school students aged 12–15 years using a latent class regression model. A multinomial logistic regression model was used to identify predictors of the cluster membership.
Results
A total of 25,566 students were included in the analysis, of which 88% were classified as having low-risk behaviors reporting only moderate alcohol use; 11% as having moderate-risk behaviors, such as driving under the influence of alcohol, fighting, carrying a weapon, and alcohol and tobacco use; and 0.6% as having high-risk behaviors, such as use of illicit drugs, particularly kratom and cannabis. Males, older students, those with a poor school performance, not living with parents, drug use by family members and peers, and having a low level of perceived disdain from their friends if they used drugs were significant risk factors for being in the moderate- and high-risk behavior classes.
Conclusions
Alcohol, tobacco and drug use, as well as other health-risk behaviors such as fighting, are clustered in Thai secondary school students. This result highlights the importance of comprehensive prevention and education strategies, particularly for moderate to high-risk groups.
... 47). Tanguay (2011) speculated that 4 Â 100 use began in Thailand sometime around 2006. In one district, Tanguay found that 21 out of 39 villages reported use of 4 Â 100. ...
... Furthermore, it is prohibited to plant or cultivate kratom, and existing kratom plants are supposed to be removed. As an example of kratom enforcement in Thailand, in 2009, 20,877 kg of kratom were seized in 5485 cases, which led to the arrests of 7388 people (Tanguay, 2011). Additionally, as Hassan et al. (2013) noted, in Malaysia, the other country in which kratom has a long history, kratom was inserted into the country's Poison Act during 2003. ...
Kratom is a plant native to Southeast Asia. It has been used for hundreds, if not thousands, of years in traditional medicine within that region. Kratom is a rare substance, due to it having both stimulant and narcotic properties. Kratom use has spread to regions outside of its native geographic range, and these countries are simultaneously considering both the benefits kratom could hold for patients and the misuse that could occur among drug users. Within the United States, after reports of increasing kratom use, the Drug Enforcement Administration (DEA) announced its intention to regulate the plant on an emergency basis. After considerable public and legislative backlash, the DEA backed off of this decision. To date, no federal regulation exists within the United States, and only a few states have regulations. This chapter discusses kratom use within Southeast Asia and the growing body of research documenting the potential medical benefits as well as the abuse liability of kratom. It concludes by discussing the drug regulation system within the United States and the potential hurdles kratom might face before becoming a recognized part of American pharmacopeia.
... Traditionally, folk healers have combined kratom with several mixtures of Thai herbs to induce health-promoting effects [5]. Furthermore, the traditional use of kratom is not perceived as 'drug use' and does not lead to discrimination among users [6]. ...
Kratom (Mitragyna speciosa) leaves are commonly used to enhance endurance and treat various diseases. This study evaluated the effect of kratom leaf fermentation with Lactobacillus rhamnosus. Antibacterial activity was investigated against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Escherichia coli, and E. coli O157:H7. Biofilm inhibition and eradication assays were also performed. Antioxidant properties were determined by measuring the total phenolic and flavonoid content and DPPH and ABTS scavenging activities. Nitric oxide and TNF-α, IL-1β, and IL-6 expressions in LPS-stimulated RAW 264.7 macrophage cells were also measured. Aqueous kratom extract exhibited promising effects against free radicals and pro-inflammatory cytokines. Notably, all fermented kratoms showed significant antibacterial activity against the tested pathogens and antibiofilm formation by S. aureus and MRSA. Furthermore, the eradication of established biofilms of fermented kratoms was observed in S. aureus (day 2, 50 mg/mL) and E. coli (day 2, 100 mg/mL and day 4, 50 mg/mL). To the best of our knowledge, this study is the first to report that fermented and non-fermented kratoms could be nutraceutical sources of antibacterial, antibiofilm, antioxidant, and anti-inflammatory substances against related diseases and can be applied further in dietary or cosmetic products with health-promoting effects.
... M. speciosa is widely grown in Southeast Asian nations such as Indonesia, Malaysia, and Thailand, mostly for its leaves [7,8]. Indonesia is known to cultivate M. speciosa for global exportation, especially to Europe and North America [9,10]. In Malaysia, the trees of M. speciosa are often grown by villagers in their backyards for consumption [11,12]. ...
The fresh leaves of Mitragyna speciosa (Korth.) Havil. have been traditionally consumed for centuries in Southeast Asia for its healing properties. Although the alkaloids of M. speciosa have been studied since the 1920s, comparative and systematic studies of metabolite composition based on different leaf maturity levels are still lacking. This study assessed the secondary metabolite composition in two different leaf stages (young and mature) of M. speciosa, using an untargeted liquid chromatography-electrospray ionisation-time-of-flight-mass spectrometry (LC-ESI-TOF-MS) metabolite profiling. The results revealed 86 putatively annotated metabolite features (RT:m/z value) comprising 63 alkaloids, 10 flavonoids, 6 terpenoids, 3 phenylpropanoids, and 1 of each carboxylic acid, glucoside, phenol, and phenolic aldehyde. The alkaloid features were further categorised into 14 subclasses, i.e., the most abundant class of secondary metabolites identified. As per previous reports, indole alkaloids are the most abundant alkaloid subclass in M. speciosa. The result of multivariate analysis (MVA) using principal component analysis (PCA) showed a clear separation of 92.8% between the young and mature leaf samples, indicating a high variance in metabolite levels between them. Akuammidine, alstonine, tryptamine, and yohimbine were tentatively identified among the many new alkaloids reported in this study, depicting the diverse biological activities of M. speciosa. Besides delving into the knowledge of metabolite distribution in different leaf stages, these findings have extended the current alkaloid repository of M. speciosa for a better understanding of its pharmaceutical potential.
... Its leaves are ovate-acuminate in shape, with glossy dark green color and could grow to over 14-20 cm in length, and 7-12 cm wide (Raffa, 2014;Raffa et al., 2013;Ratsch, 2005). Kratom has been used traditionally for various treatments, including fatigue, cough, pain, colds, diarrhea, diabetes, hypertension, increased stamina and sexual prowess, and opium withdrawal (Suwanlert, 1975;Chua and Schmelzer, 2001;Ratsch, 2005;Assanangkornchai et al., 2007;Tanguay, 2011;Singh et al., 2019). Due to its opioid activity, kratom gaining *Corresponding author : Endang Lukitaningsih Email : lukitaningsih_end@ugm.ac.id popularity as a recreational psychoactive drug (Prozialeck et al., 2012;Cinosi et al., 2015). ...
The extraction of kratom (M. speciosa) leaf powder was optimized with preliminary extraction to be further optimized with the Box-Behnken experimental design. The individual and interactive effects of process variables (sample-to-solvent ratio, extraction time, solvent concentration) were assessed. The preliminary extraction results showed that ultrasound-assisted extraction (UAE) and methanol were chosen for further optimization. The experimental data were analyzed by Pareto analysis of variance (ANOVA) and second-order polynomial models were developed using multiple regression analysis. The model developed showed a good fit with the experimental data with a high coefficient of correlation (R2) and predictive ability (predicted R2). An optimization study was performed and the optimal extraction conditions were sample-to-solvent ratio value 1.5:10; extraction time of 10 minutes, and methanol concentration of 100%.
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 ‐OCH 3 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 ( R ² = 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.
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 (Mitragyna speciosa Korth. Havil) has been considered a narcotic drug for years, barred by the law in many parts of the world, while extensive research over the past few decades proves its several beneficial effects, some of which are still in ambiguity. In many countries, including Thailand, the indiscriminate use and abuse of kratom have led to the loss of life. Nonetheless, researchers have isolated almost fifty pure compounds from kratom, most of which are alkaloids. The most prevalent compounds, mitragynine and 7-hydroxy mitragynine, are reported to display agonist morphine-like effects on human μ-opioid receptors and antagonists at κ- and δ-opioid receptors with multimodal effects at other central receptors. Mitragynine is also credited to be one of the modulatory molecules for the Keap1-Nrf2 pathway and SOD, CAT, GST, and associated genes’ upregulatory cascades, leading it to play a pivotal role in neuroprotective actions while evidently causing neuronal disorders at high doses. Additionally, its anti-inflammatory, antioxidative, antibacterial, and gastroprotective effects are well-cited. In this context, this review focuses on the research gap to resolve ambiguities about the neuronal effects of kratom and demonstrate its prospects as a therapeutic target for neurological disorders associated with other pharmacological effects.
Purpose of Review
Use of “kratom” products, derived from the bioactive botanical Mitragyna speciosa have increased amidst US polydrug use epidemics. Kratom alkaloids interact with opioid, serotonergic, adrenergic, and other receptors and regular users have described experiencing a wide range of effects. Some with polydrug use histories have reported using kratom as a substitute for other drugs or to nonmedically self-manage substance use disorder (SUD) symptoms. Data describing this remain scare and come from self-report. We review this literature describing kratom use as a drug substitute, or as a nonmedical “self-treatment” for attenuating dependence or SUD symptoms.
Recent Findings
Kratom products have been documented as being used as a licit and illicit opioid substitute. Use to reduce alcohol or stimulant consumption is less well documented. Although prior and current polydrug use appear common among a some kratom users, it is unclear if co-use is contemporaneous or concomitant. Temporal order of use initiation is typically undocumented. Use for energy and recreation are also increasingly reported.
Summary
Data on kratom consumption come primarily from self-report with significant limitations. Until controlled human laboratory studies have been conducted, we can presently only describe what is known about human kratom use based on self-report. Such data describe real-world kratom use, leaving unaddressed human abuse liability or therapeutic potential of kratom alkaloids. Clinicians should be mindful of use motivations among people with SUD histories, sensitively assessing use. The paucity of data highlights the urgent need to increase funding and research for understanding kratom’s effects in humans.
Purpose of Review
This systematic review examines case reports of kratom physical dependence or addiction, focusing on assessment, diagnosis, and treatment methods and the completeness of the clinical data presented.
Recent Findings
Most peer-reviewed clinical literature on kratom physical dependence and addiction comes in the form of case reports. However, these reports often provide incomplete descriptions of complex circumstances, and there remain no standardized assessment, diagnostic, or treatment methods for patients presenting with these morbidities.
Summary
Many reports were difficult to interpret due to missing information. Despite the lack of standardized assessment and diagnostic tools for kratom addiction, withdrawal, or dependence, medications for opioid use disorder were frequently prescribed, which is problematic for opioid naïve patients. Findings suggest that case reports involving kratom should include established standardized assessments of history and symptomatology, incorporating laboratory testing where possible. Development of best practices for treatment of kratom-associated dependence or addiction is warranted.
Purpose of Review
The rising public interest in kratom is paralleled by concerns of adverse outcomes, particularly overdose. Such claims span a multitude of reporting modalities, including case reports, analyses of data from poison control and coroners’ reports, and warnings from government agencies. Here we evaluate the literature in efforts to assess kratom’s potential overdose risk. A keyword search of online literature databases identified 12 preclinical studies, 23 case reports, and 15 observational studies/reports meeting our pre-selected criteria.
Recent Findings
Case reports describe outcomes where kratom products are coingested with illicit substances and pharmaceuticals. Opioids are common coingestants, and presentations describe pulmonary edema and findings resembling opioid overdoses. However, seizures and hyperadrenergic features are also common. Where reported, post-mortem mitragynine (MG) concentrations are inconclusive of attributed toxicities. Animal studies found oral LD50s in the range of 200–960 mg/kg for MG, and 200–591 mg/kg for Malaysian total alkaloid extract. Deaths were preceded by restlessness, tremors, and convulsions. Analyses of a variety of reported toxicities yield signs and symptoms that resemble hyperadrenergic components, with autopsies finding coingestants in addition to alkaloids.
Summary
As with any compound ingested in large quantities, it is possible to develop lethal toxicities with kratom in a dose-dependent fashion. Use via the traditional mode of consumption, such as chewing or brewing the leaves as a tea, would require a tremendous amount of kratom to be ingested. The currently available kratom products, and pure alkaloid isolates, greatly increase this risk, in addition to combining kratom with illicit substances, and pharmacokinetic/pharmacodynamic interactions.
Background: Kratom (Mitragyna speciosa Korth.) products are increasingly endorsed for self-management of multiple ailments, including as opioid substitution. The FDA has expressed that there is no evidence to indicate that this botanical is safe or effective for any medical use.
Objective: We systematically review the current state of the literature concerning the impact of kratom and its alkaloids in all paradigms that involve opioids.
Methods: A keyword search of online literature databases identified 16 preclinical studies, 25 case reports, and 10 observational studies meeting our pre-selected criteria.
Results: All rodent models support alkaloids’ action on opioid receptors, translating in their ability to mitigate opioid withdrawal. Some studies found mitragynine (MG) to have less reinforcing properties than morphine, and possessing tolerance-sparing properties when coadministered with morphine. Two studies that assessed 7-hydroxymitragynine (7OHMG) found it to substitute for morphine with potential for tolerance and dependence. Aside from addiction development, case reports outline a variety of confounding toxicities. Ten surveys of users, some conducted with assistance from pro-kratom lobbying organizations, find a high self-reported efficacy as an opioid substitute, with minimal reported adverse effects.
Conclusion: With no reported controlled human clinical trials, in the light of rising concerns surrounding kratom’s liabilities, there is insufficient evidence to allow any conclusions to be drawn. Case reports and observational studies carry significant bias toward harm and efficacy, respectively. Existing animal studies are heterogeneous in methodology and ultimately findings, with concern for interspecies variability and human translatability. Further research should investigate the safety and efficacy of using kratom alkaloids as opioid substitutes.
Ukraine today does not regulate the sale of products made of Kratom (Mitragyna speciosa Korth. (from the family Rubiaceae) and does not take measures to control the quality and safety of this product, despite its rapid spread throughout the country. Аim of the Work is to summarize the results of scientific research on the toxicity of alternative opioids contained in Mitragyna speciosa and combined products based on them. Material and methods. Reports from the World Health Organization (WHO), the European Monitoring Center for Drugs and Drug Addiction (EMCDDA), the United Nations Office on Drugs and Crime, the results of scientific reviews and individual studies on biochemistry, toxicology, forensic identification of substances contained in products made from Mitragyna speciosa, over the past 10 years (Elsevier, PubMed, ToxNet). Results and Discussion. Recently, kratom has been cultivated on different continents and entered the market under the name "Kратом", in English-language sources - "Kratom". Kratom leaves are dried and sold in the form of green powder, tablets, capsules, extracts and gummies. In Ukraine, kratom is sold under hundreds of commercial names on the Internet as "Kratom", "Kratom product", "Kratom organic tea", "Kratom ethnic tea", "Kratom tea" and others. More than 40 structurally related alkaloids, as well as several flavonoids, terpenoid saponins, polyphenols and various glycosides were found in kratom leaves. The pharmacological and toxic effects of kratom for most of its components have not been studied enough. Like other dietary supplements, kratom products should be standardized for alkaloids, microbial contamination, pesticides, heavy metals, residual solvents, benzo(a)pyrene, aflatoxins, etc., with appropriate labeling requirements. Conclusions. Quality products should enter the Ukrainian market - standardized leaf extract of kratom, or other safe products made on its basis. However, recent studies show that mitraginine contained in kratom has great potential for medical science as a model for developing new approaches in very relevant areas of medicine: to treat pain and get rid of opioid dependence. Key Words: Mitragyna speciosa, alternative opioids, toxicity.
Neurophysiological characteristics of long-term Kratom users have been challenged for identification due to the lack of evidence. Long-term and high Kratom consumption caused concern, particularly in older adults. Thus, the study aims to explore EEG biomarkers in long-term Kratom users (LKU) based on consumer-grade EEG systems. The fifty-two participants were collected EEG using MUSE portable system during resting-state to examine EEG biomarkers with the proposed features: theta/alpha ratio and power variance function (PVF) in theta and alpha bands. The statistical analysis was further carried out to test the existent difference between controls and LKU in various age ranges (≤50 and >50 years of age) and different doses of Kratom consumption (low to high doses and very high dose). Subsequently, the statistical-based EEG biomarkers were extracted and performed classification among four classifiers (Random forest, Support vector machine,
-Nearest Neighbor, and Logistic regression. As a result, the TAR ratio was remarkably different between groups over 50 years of age. Furthermore, TAR and PVF in the alpha band were dominant in those who consumed Kratom at a very high dose and was classified well by support vector machine using the features combination (accuracy at 83.33% ± 10.24, sensitivity at 90.00% ± 10.00, specificity at 75.00% ± 13.44). Our preliminary results concluded that the proposed EEG features were an important EEG biomarker for LKU with a large effect size. This finding led us to the promising aspect of applying machine learning-based EEG biomarkers to screen the overdose of Kratom consumption in the future.
Mitragyna speciosa (Korth.) Havil. [MS], or “kratom” in Thai, is the only narcotic species among the four species of Mitragyna in Thailand, which also include Mitragyna diversifolia (Wall. ex G. Don) Havil. [MD], Mitragyna hirsuta Havil. [MH], and Mitragyna rotundifolia (Roxb.) O. Kuntze [MR]. M. speciosa is a tropical tree belonging to the Rubiaceae family and has been prohibited by law in Thailand. However, it has been extensively covered in national and international news, as its abuse has become more popular. M. speciosa is a narcotic plant and has been used as an opium substitute and traditionally used for the treatment of chronic pain and various illnesses . Due to morphological disparities in the genus, the identification of plants in various forms, including fresh leaves, dried leaf powder, and finished products, is difficult. In this study, DNA barcoding combined with high-resolution melting (Bar-HRM) analysis was performed to differentiate M. speciosa from allied Mitragyna and to assess the capability of Bar-HRM assays to identify M. speciosa in suspected kratom or M. speciosa -containing samples. Bar-HRM analysis of PCR amplicons was based on the ITS2, rbc L, trn H -psb A , and mat K DNA barcode regions. The melting profiles of ITS2 amplicons were clearly distinct, which enabled the authentication and differentiation of Mitragyna species from allied species. This study reveals that DNA barcoding coupled with HRM is an efficient tool with which to identify M. speciosa and M. speciosa -containing samples and ensure the safety and quality of traditional Thai herbal medicines.
Abstrak Kratom (Mitragina speciosa) merupakan tanaman herbal asal Indonesia. Daun kratom memiliki banyak manfaat sebagai obat herbal seperti obat demam, diare, dan penghilang nyeri. Efek sedatif dan stimulan pada sistem syaraf pusat merupakan efek samping daun Kratom. Harga yang murah dan kemudahan dalam memperoleh daun Kratom menjadi penyebabkan utama daun Kratom banyak disalahgunakan sebagai penganti narkotika terlarang lainnya. Daun kratom masuk kedalam new psychoactive substances (NPS) atau narkotika jenis baru karena memiliki efek ketergantungan dan bertindak seperti opioid lainnya seperti heroin dan ganja.Daun kratom dapat diperoleh dengan mudah dengan pembelian secara online. Umumnya daun Kratom dijual dalam bentuk olahan yang sulit untuk dikenali bentuknya, seperti sampel dalam penelitian ini berupa bubuk dan serbuk daun kratom. Pengujian yang dilakukan untuk identifikasi daun Kratom dapat dilakukan dengan cara botani dan cara kimia. Metode botani dicari karakteristik spesifik daun kratom dengan uji mikroskopik, dan secara kimia yang menjadi salah satu senyawa penciri daun kratom adalah mitragynine. Pengembangan metode identifikasi mitragynine dilakukan dengan metode GC-MS, KLT, dan KLT-densitometri. Pengembang metode Isolasi mitagynine juga dilakukan karena sulitnya memperoleh standar baku dipasaran. Metode isolasi yang sederhana dan cepat dilakukan dengan metode KLT-Preparatif yang mana hasil isolasinya menunjukkan puncak tunggal pada hasil uji GC-MS. Kata kunci: Identifikasi, Isolasi, Kratom, Mitragyna speciosa, mitagynine
Background
Amidst the opioid crisis, many people are turning to plant-based kratom for self-treatment of pain, opioid addiction, and for recreational use. Its legality is variable and its safety and medicinal effects are not agreed upon. It is broadly available from Internet Kratom Vendors (IKVs).
Methods
An examination of the online marketplace for kratom was conducted to provide context to the market amidst regulatory attempts by the Food and Drug Administration (FDA) and state legislatures. A complex search strategy identified 663 English-language IKVs selling kratom for home delivery. The 100 most popular were selected for in-depth content analysis. IKVs were visited once for content analysis data collection in December, 2017 and revisited in April 2018 to assess responses to FDA action. IKV website and social media profiles were coded for topics including location, payment and shipping options, age verification, health warnings and disclaimers, and grassroots advocacy regarding upcoming state/federal regulations.
Results
Forty-seven percent of IKVs claimed that kratom provides pain relief, 25% claimed it provides relief from opioid withdrawal, 81% featured a disclaimer that kratom is addictive, 54% stated that kratom is not FDA approved, and 66% featured disclaimers that it was not intended for consumption. Only 5% of vendors advertised effective age verification (such as verifying age at delivery). Compliance on the vendor's part with state and local bans varied by ban location, with only 27% prohibiting sales to Rhode Island while 65% did not ship to Indiana.
Conclusions
IKVs provide easy access to a wide variety of unregulated intoxicating products with poor age verification and low adherence to US state- and local-level restrictions. There is a high prevalence of vendors featuring health claims forbidden by the Food and Drug Administration. Lessons learned from regulating the Internet cigarette sales industry could be effectively applied to IKVs with future efforts.
Kratom (Mitragyna speciosa), an indigenous medicinal plant of Southeast Asia, is believed to be harmful. We compared the perceptions toward kratom use among kratom users and non-users in Malaysia. 356 respondents (137 kratom users and 219 non-users) were recruited for this cross-sectional study. The majority of respondents were male (60%, n = 212/356), Malays (88%), and 51% were ≥37 years old. Non-users showed higher unadjusted odds of reporting a perception that kratom use can cause addiction (OR = 6.72, CI: 3.91–11.54, p < .0001), withdrawal symptoms (OR = 7.58, CI: 4.62–12.42, p < .0001), illicit drug use problems (OR = 10.12, CI: 6.14–16.68, p < .0001), impaired social-functioning (OR = 12.05, CI: 7.24–20.05, p < .0001), and health problems (OR = 10.44, CI: 6.32–17.24, p < .0001). Similarly, non-users viewed kratom policies differently from kratom users, displaying increased odds of reporting the belief that kratom use and sales must be regulated with stringent laws (OR = 5.75, CI: 3.61–9.18, p < .0001), and kratom should be regulated instead under the Dangerous Drugs Act 1952 to overcome kratom use problems (OR = 8.26, CI: 4.94–13.82, p < .0001). Because of the disconnect in kratom use perceptions and personal experiences between kratom users and non-users, hastily criminalizing kratom without investigating carefully its scientific merits can significantly impede future kratom research.
This study sought to determine the relationship between kratom (Mitragyna speciosa) initiation and regular consumption of illicit drugs and HIV risk behaviors in a cohort of illicit drug users in Malaysia. 260 illicit drug users with current kratom use were recruited through convenience sampling for this cross-sectional study. All were male, with the majority being Malays (95%, n = 246/260). Results suggest that kratom initiation was associated with significant decrease in the regular use of heroin (odds ratio (OR) = 0.50, 95% confidence interval (CI): 0.40– 0.72; p = .0001), methamphetamine (OR = 0.23, CI: 0.16– 0.35; p < .0001), and amphetamine (OR = 0.17, CI: 0.09– 0.34; p < .0001). Kratom initiation was also associated with reduction in regular HIV risk behaviors such as having sex with sex workers (OR = 0.20, CI: 0.12–0.32; p < .0001), using drugs before sexual intercourse (OR = 0.20, CI: 0.13– 0.31; p < .0001), injecting behaviors (OR = 0.10, CI: 0.04– 0.25; p < .0001), sharing of injection equipment (OR = 0.13, CI: 0.04– 0.43; p < .0001), and injecting with other injection drug users (IDUs) (OR = 0.07, CI: 0.02– 0.24; p < .0001).
Mitragyna speciosa, commonly known as Ketum or Biak in Malaysia and Kratom in Thailand, is a native plant to Southeast Asia and has various pharmacological benefits. Mitragynine (MG) is the principal alkaloid found in the leaves of Mitragyna speciosa and has been reported to be responsible for the plant’s therapeutic actions. Traditionally, local communities use Kratom preparations for relief from different types of pain. The potential analgesic effects of MG using rodent models have been reported in literatures. We have reviewed the published analgesic and pharmacokinetic studies and all of these findings showed the routes of drug administration, doses employed, and type of vehicles used to solubilize the drug, varied considerably; hence this posted difficulties in predicting the drug’s pharmacokinetic-response relationship. A rational approach is warranted for accurate prediction of dose-response relationship; as this is essential for the development of MG as an alternative medicinal drug for pain management. PKPD modeling would serve as a better method to understand the dose-response relationship in future MG preclinical and clinical studies
Purpose of Review
This review describes case reports for patients with kratom-associated adverse events in order to assist clinicians with patient management. A stepwise approach is proposed for assessing active kratom users as well as considerations for the management of toxicities or withdrawal.
Recent Findings
Multiple in vitro and in vivo studies illustrate the pharmacologic and toxicologic effects of kratom extract. No randomized controlled trials in humans exist that assess the safety and efficacy of the substance. Cross-sectional surveys from active users and reports from poison control centers have shown acute and chronic physiological and psychological adverse events.
Summary
Reports of adverse effects associated with kratom use have demonstrated hypothyroidism, hypogonadism, hepatitis, acute respiratory distress syndrome, posterior reversible encephalopathy syndrome, seizure, and coma. Overdose toxidrome leads to respiratory failure, cardiac arrest, and fatalities. Adult and neonatal withdrawal symptoms have also occurred. Clinicians should be aware of the risks and benefits of kratom use.
Background
Kratom ( Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events.
Aims
This study details the characteristics of such fatalities and provides a ‘state-of-the-art’ review.
Methods
UK cases were identified from mortality registers by searching with the terms ‘kratom’, ‘mitragynine’, etc. Databases and online media were searched using these terms and ‘death’, ‘fatal*’, ‘overdose’, ‘poisoning’, etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis.
Results
Typical case characteristics ( n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine alone was identified/implicated in 23% of cases. Poly substance use was common (87%), typically controlled/recreational drugs, therapeutic drugs, and alcohol. Death cause(s) included toxic effects of kratom ± other substances; underlying health issues.
Conclusions
These findings add substantially to the knowledge base on kratom-associated deaths; these need systematic, accurate recording. Kratom’s safety profile remains only partially understood; toxic and fatal levels require quantification.
Background: Mitragyna speciosa (Korth.) or kratom is an indigenous medicinal plant of Southeast Asia. Kratom is widely reported to have dose-dependent effects based on available literature, but to our knowledge, this has not been established conclusively. Objective: This study sought to evaluate if kratom use produces dose-dependent effects, with a stimulant effect at low doses and a sedative effect at high doses, in a sample of regular kratom users. Methods: A total of 63 regular kratom users participated in this cross-sectional study. The Brief-Biphasic Alcohol Effects Scale (B-BAES) was used to determine subjects self-report kratom use experiences. Results: Almost all in the sample were male (98%, n = 62/63), and the majority of subjects were Malays (94%, n = 59/63). The mean age of the subjects in the sample was 43.8 years (SD = 12.1). Seventy-five percent (n = 47/63) have >5 years kratom use history, and 65% (n = 41/63) consumed >3 glasses of kratom daily. Results from first test showed no significant difference in the stimulant (t61 =0.371, p < .331) and sedative effects (t61 =502, p < .759) between those who consumed >3 glasses a day or less than this amount, regardless of duration of use. In the second test, no significant differences in the mean scores were found among those who consumed >3 glasses daily or less than this amount among short-term or long-term uses. Conclusions: Daily kratom use produced both stimulant and sedative effects but they were not statistically significantly associated with the dose consumed, both among short-term and long-term users in our sample.
Objective:
Kratom preparations have raised concerns of public health and safety in the United States. This paper analyzed the patterns and predictors of kratom use by four U.S. regions according to the U.S. Census.
Method:
An anonymous cross-sectional online survey yielded 8,049 valid responses. The data were categorised by regions (Northeast, South, Midwest, and West) and analyzed for the following predictors: age, gender, marital status, ethnicity, employment status, insurance coverage, education, and household income.
Results:
After adjusting for state population, the survey response rates were highest from Oregon, Idaho, and Florida. Kratom use was significantly lower for both prescription drug dependency and acute or chronic pain in the Northeast region than the rest of the country. Multiple logistic regression models found that gender, employment, and education were significant on the regional level. Higher education was associated with lower kratom use for an illicit drug dependency (p = .002) independent of region whereas men were less likely to use kratom for acute or chronic pain in the Northeast (p < .001) but more likely in the Midwest (p = .041).
Conclusions:
The regional pattern of kratom use differed from opioid use data in both demographics and trend direction warranting further investigation.
Kratom is a psychoactive herb that has stimulant properties at low doses and has opioid-like properties at higher doses. It has been used for centuries in southeast Asia as a stimulant but has gained increasing popularity as a substitute for opioids in western countries as it is easily available. As most cases of kratom use involve other drugs too, the Food and Drug Administration (FDA) has stopped short of restricting kratom due to difficulty in assessing the adverse effects of kratom alone. We present the case of a young healthy 35-year-old man who suffered a cardiac arrest due to kratom use with no other coingestants. He was subsequently intubated and found to have systolic dysfunction and small brain infarcts. Fortunately, he made a successful recovery and was discharged after a stay at thebehavioural health centre. Our case highlights the potential adverse effects of kratom and the need to regulate its use.
Background:
Mitragynine is the major alkaloid of Mitragyna speciosa (Korth.) or Kratom, a psychoactive plant widely abused in Southeast Asia. While addictive effects of the substance are emerging, adverse cognitive effects of this drug and neuropharmacological actions are insufficiently understood.
Aims:
In the present study, we investigated the effects of mitragynine on spatial learning and synaptic transmission in the CA1 region of the hippocampus.
Methods:
Male Sprague Dawley rats received daily (for 12 days) training sessions in the Morris water maze, with each session followed by treatment either with mitragynine (1, 5, or 10 mg/kg; intraperitoneally), morphine (5 mg/kg; intraperitoneally) or a vehicle. In the second experiment, we recorded field excitatory postsynaptic potentials in the hippocampal CA1 area in anesthetized rats and assessed the effects of mitragynine on baseline synaptic transmission, paired-pulse facilitation, and long-term potentiation. Gene expression of major memory- and addiction-related genes was investigated and the effects of mitragynine on Ca2+ influx was also examined in cultured primary neurons from E16-E18 rats.
Results/outcomes:
Escape latency results indicate that animals treated with mitragynine displayed a slower rate of acquisition as compared to their control counterparts. Further, mitragynine treatment significantly reduced the amplitude of baseline (i.e. non-potentiated) field excitatory postsynaptic potentials and resulted in a minor suppression of long-term potentiation in CA1. Bdnf and αCaMKII mRNA expressions in the brain were not affected and Ca2+ influx elicited by glutamate application was inhibited in neurons pre-treated with mitragynine.
Conclusions/interpretation:
These data suggest that high doses of mitragynine (5 and 10 mg/kg) cause memory deficits, possibly via inhibition of Ca2+ influx and disruption of hippocampal synaptic transmission and long-term potentiation induction.
In Asia, Mitragyna speciosa (e.g., “kratom”) has been used to mitigate alcohol and drug dependence. Some preliminary findings suggest kratom’s potential use as an informal harm-reduction method in the United States, such as an opioid substitute or as a means of lessening opioid withdrawal symptoms. To determine correlates of past-year kratom use among a sample of polysubstance users enrolled in residential recovery programs in Kentucky, an anonymous survey was completed by clients in April 2017. Logistic regression was used to identify significant associations with past-year kratom use. Of the final sample (N = 478), 10.4% reported past-year kratom use. Past-year heroin use, but not past-year prescription opioid (e.g., oxycodone, hydrocodone) use, was significantly associated with kratom use, such that individuals who reported past-year heroin use were 2.5 times more likely to also report past-year kratom use. Non-prescribed buprenorphine (i.e., Suboxone) use partially mediated the relationship between past-year heroin and kratom use by explaining 36% of the association between the two drugs. Though amphetamines were highly preferred, past-year use was negatively correlated with past-year kratom use. Rates of past-year kratom use were lower than rates of alcohol and illicit drug use. Kratom was not preferred over heroin or prescription opioids.
The abuse of psychotropic substances is a well-known phenomenon, and many of them are usually associated with ancestral traditions and home remedies. This is the case of Mitragyna speciosa (kratom), a tropical tree used to improve work performance and to withstand great heat. According to several published studies, the main reasons for kratom consumption involve improving sexual performance and endurance, but also social and recreational uses for the feeling of happiness and euphoria; it is also used for medical purposes as a pain reliever, and in the treatment of diarrhea, fever, diabetes, and hypertension. However, this plant has gained more popularity amongst young people over the last years. Since it is available on the internet for purchase, its use is now widely as a drug of abuse, namely as a new psychoactive substance, being a cheaper alternative to opioids that does not require medical prescription in most countries. According to internet surveys by the European Monitoring Centre for Drugs and Drug Addiction in 2008 and 2011, kratom was one of the most widely supplied new psychoactive substances. The composition of kratom is complex; in fact, more than 40 different alkaloids have been identified in Mitragyna speciosa so far, the major constituent being mitragynine, which is exclusive to this plant. Besides mitragynine, alkaloids such as corynantheidine and 7-hydroxamitragynine also present pharmacological effects, a feature that may be attributed to the remaining constituents as well. The main goal of this review is not only to understand the origin, chemistry, consumption, and analytical methodologies for analysis and mechanism of action, but also the use of secondary metabolites of kratom as therapeutic drugs and the assessment of potential risks associated with its consumption, in order to aid health professionals, toxicologists, and police authorities in cases where this plant is present.
Kratom (Mitragyna speciosa Korth.) is traditionally used in Southeast Asia for its medicinal value and psychoactive properties. Nonetheless, cessation from regular kratom use is reported to cause unpleasant dose-dependent withdrawal symptoms. This study aims to evaluate the severity of pain and sleep problems following the cessation of kratom tea/juice consumption among regular kratom users. A total of 170 regular users were recruited through snowball sampling for this cross-sectional study. The Brief Pain Inventory (BPI) and Pittsburgh Sleep Quality Index (PSQI) scales were administered to assess the severity of pain and sleep problems. Most participants experienced moderate pain intensity (84%) and moderate pain interference (70%) during kratom cessation; 46% experienced more sleep problems during kratom cessation. Individuals who consumed ≥4 glasses of kratom tea/juice (about 76–115 mg of mitragynine) daily had higher odds of reporting some pain interference (OR: 2.0; CI: 1.04–3.93: p < .028), and sleep problems during kratom cessation (OR: 2.0; CI: 1.08–3.68: p < .020), as compared to those who consumed 1–3 glasses of kratom tea/juice daily. However, the effects were still relatively mild. Cessation from regular kratom tea/juice consumption is not associated with prolonged pain and sleep problems, as compared to those reported for opioid analgesics.
RationaleConsideration by the US Drug Enforcement Administration and Food and Drug Administration of placing kratom into Schedule I of the Controlled Substances Act (CSA) requires its evaluation of abuse potential in the context of public health. Objective
The objective of the study is to provide a review of kratom abuse potential and its evaluation according to the 8 factors of the CSA. ResultsKratom leaves and extracts have been used for centuries in Southeast Asia and elsewhere to manage pain and other disorders and, by mid-twentieth century, to manage opioid withdrawal. Kratom has some opioid effects but low respiratory depression and abuse potential compared to opioids of abuse. This appears due to its non-opioid-derived and resembling molecular structure recently referred to as biased agonists. By the early 2000s, kratom was increasingly used in the US as a natural remedy to improve mood and quality of life and as substitutes for prescription and illicit opioids for managing pain and opioid withdrawal by people seeking abstinence from opioids. There has been no documented threat to public health that would appear to warrant emergency scheduling of the products and placement in Schedule I of the CSA carries risks of creating serious public health problems. Conclusions
Although kratom appears to have pharmacological properties that support some level of scheduling, if it was an approved drug, placing it into Schedule I, thus banning it, risks creating public health problems that do not presently exist. Furthermore, appropriate regulation by FDA is vital to ensure appropriate and safe use.
Purpose:
This article reviews the pharmacology, clinical utility, adverse effects, and abuse potential of kratom.
Summary:
The leaves of M. speciosa contain the biologically active alkaloids of kratom. Kratom exerts opioid and α-2 receptor agonistic effects as well as antiinflammatory and parasympathetic-impeding effects. There are no published human pharmacologic, pharmacokinetic, or drug interaction studies on kratom or mitragynine, making it virtually impossible to fully understand kratom's therapeutic potential and risks and the populations most likely to benefit or experience harm from its use. Kratom has been used to ameliorate opioid withdrawal symptoms but also induces withdrawal. Human pharmacologic, pharmacokinetic and clinical data are of low quality precluding any firm conclusions regarding safety and efficacy. Respiratory depression has not been commonly reported but kratom does cause a host of adverse effects without clear guidance for how they should be treated. There are numerous assessments where people have been unable to stop using kratom therapy and withdrawal signs and symptoms are problematic. Kratom does not appear in normal drug screens and, when taken with other substances of abuse, may not be recognized. Thirty-six deaths have been attributed to kratom, and the Food and Drug Administration issued a public health warning about the substance in November 2017.
Conclusion:
Kratom exerts opioid and α-2 receptor agonistic effects as well as antiinflammatory and parasympathetic-impeding effects. Human pharmacologic, pharmacokinetic, and clinical data are of low quality precluding any firm conclusions regarding safety and efficacy.
Objective:
Kratom (Mitragyna speciosa. Korth) is an indigenous medicinal plant of Southeast Asia. This review paper aims to describe the trends of kratom use in Southeast Asia.
Design:
A literature review search was conducted through ScienceDirect, Scopus, ProMed and Google Scholar. Twenty-five articles illustrating kratom use in humans in Southeast Asia were reviewed.
Results:
Kratom has long been used by rural populations in Southeast Asia as a remedy for common ailments, to fight fatigue from hard manual work, as a drink during social interaction among men, and in village religious functions. Studies based on self-reports suggest that prolonged kratom use does not result in serious health risks or impair social functioning. Two recent trends have also emerged: (a) Kratom is reportedly being used to ease withdrawal from opioid dependence in rural settings; whereas (b) in urban areas, adulterated kratom cocktails are being consumed by younger people to induce euphoria.
Conclusions:
Legal sanctions appear to have preceded serious scientific investigations into the claimed benefits of ketum. More objective-controlled trials and experiments on humans need to be conducted to validate self-report claims by kratom users in the community.
Ethnopharmacological relevance:
The genus Mitragyna (Rubiacaeae) has been traditionally used in parts of Africa, Asia and Oceania. In recent years, there has been increased interest in species of Mitragyna with the introduction of products to western markets and regulatory uncertainty.
Aim of the study:
This paper reviewed the traditional ethnomedicinal uses of leaves for species belonging to the genus Mitragyna with reference to the botany and known chemistry in order to highlight areas of interest for products currently being sold as kratom.
Materials and methods:
A literature search was conducted using Web of Science, Google Scholar, the Royal Museum for Central Africa, Internet Archive, Hathi Trust, and Biodiversity Heritage Library search engines in the spring of 2015, fall of 2016 and winter of 2017 to document uses of bark, leaf and root material.
Results:
Leaves of M. speciosa (kratom) had the most common documented ethnomedicinal uses as an opium substitute or remedy for addiction. Other species of Mitragyna were reportedly used for treating pain, however the mode of preparation was most often cited as topical application. Other uses of Mitragyna included treatment of fever, skin infections, and as a mild anxiolytic.
Conclusions:
Mitragyna species have been used medicinally in various parts of the world and that there is significant traditional evidence of use. Modern products that include formulations as topical application of liniments, balms or tinctures may provide effective alternatives for treatment of certain types of pains. Future research is required to establish safety and toxicology limits, medicinal chemistry parameters and the potential for different physiological responses among varying genetic populations to support regulatory requirements for Mitragyna spp.
Two cases of fatalities are reported of which the recreational use of Mitragyna speciosa (“kratom”) could be confirmed. One of these cases presents with one of the highest postmortem mitragynine concentrations published to date. Our results show that even extremely high mitragynine blood concentrations following the consumption of kratom do not necessarily have to be the direct cause of death in such fatalities as a result of an acute overdose. The two cases are compared with regard to the differences in mitragynine concentrations detected and the role of mitragynine in the death of the subjects. Irrespective of the big differences in mitragynine concentrations in the postmortem blood samples, mitragynine was not the primary cause of death in either of the two cases reported here. Additionally, by rough estimation, a significant difference in ratio of mitragynine to its diastereomers in the blood and urine samples between the two cases could be seen.
This study sought to compare the effects of Mitragyna speciosa (Korth.) Havil. extract, alkaloids fraction, and mitragynine, a μ-opioid receptor agonist, to that of morphine and oxycodone in a test of thermal nociception. In Experiment 1, male Sprague-Dawley rats were administered test articles intraperitoneally (IP) 30min prior to testing to compare the effects of M. speciosa articles to opioid reference compounds on the hotplate assay. Test articles were vehicle, 10mg/kg morphine, 3mg/kg oxycodone, 300mg/kgM. speciosa extract, 75mg/kgM. speciosa alkaloids fraction, or 30mg/kg mitragynine. To mirror consumer usage, Experiment 2 sought to determine whether M. speciosa articles retained their biological activity when given orally (PO). Test articles were vehicle, 6mg/kg oxycodone, 300mg/kgM. speciosa extract, or 100mg/kg mitragynine with hotplate tests conducted 30 and 60min after administration. Mitragynine produced antinociceptive effects similar to the reference opioid agonists when administered IP and PO routes. These data suggest M. speciosa extracts containing significant quantities of mitragynine may warrant consideration for further studies in primate self-administration models to yield insight into the abuse liability of this commercially available product.
Kratom (Mitragyna speciosa) is a psychoactive plant that has been used since at least 1836 in folk medicine in Southeast Asian countries. More recently, kratom has become widely available in the West and is used for both recreational and medicinal purposes. There has, however, been little scientific research into the short- and long-term effects of kratom in humans, and much of the information available is anecdotal. To supplement the increasing scientific understanding of kratom's pharmacology and research into its effects in animals, we report the results of a qualitative analysis of first-hand descriptions of human kratom use that were submitted to, and published by, a psychoactive substance information website (Erowid.org). Themes that emerged from these experience reports indicate that kratom may be useful for analgesia, mood elevation, anxiety reduction, and may aid opioid withdrawal management. Negative response themes also emerged, indicating potential problems and unfavorable "side" effects, especially stomach upset and vomiting. Based on our analyses, we present preliminary hypotheses for future examination in controlled, quantitative studies of kratom.
Kratom (or Ketum) is a psychoactive plant preparation used in Southeast Asia. It is derived from the plant Mitragyna speciosa Korth. Kratom as well as its main alkaloid, mitragynine, currently spreads around the world. Thus, addiction potential and adverse health consequences are becoming an important issue for health authorities. Here we reviewed the available evidence and identified future research needs. It was found that mitragynine and M. speciosa preparations are systematically consumed with rather well defined instrumentalization goals, e.g. to enhance tolerance for hard work or as a substitute in the self-treatment of opiate addiction. There is also evidence from experimental animal models supporting analgesic, muscle relaxant, anti-inflammatory as well as strong anorectic effects. In humans, regular consumption may escalate, lead to tolerance and may yield aversive withdrawal effects. Mitragynine and its derivatives actions in the central nervous system involve μ-opioid receptors, neuronal Ca2+ channels and descending monoaminergic projections. Altogether, available data currently suggest both, a therapeutic as well as an abuse potential.
The consumption of Mitragyna speciosa (MS) for its psychoactive effects is widely reported amongst people in the villages in Thailand and Malaysia even though its use is illegal.
This study examined the pattern of MS use, its reported effects and explored its potential to cause dependence.
We used both convenience and snowball-sampling methods to recruit participants in a border town between two northern states in Malaysia. Face-to-face interviews were conducted with the use of a structured questionnaire on 562 respondents who gave oral consent to participate in the study.
The response rate was 91%. The majority of the respondents (88%) reported daily use of MS. The main mode of using MS was by drinking the MS extract as tea (90%). The mean age of starting MS use was 28.3 (SD=8.1) years. A variety of reasons were given for using MS including for social and recreational needs, stamina and physical endurance, pain relief and improved sexual performance. Despite its reported usefulness in weaning off opiate addiction, 460 (87%) admitted they were not able to stop using MS. Only education level had a statistically significant association with the ability to stop or not stop the use of MS (χ(2)=31.0, df=1, p<0.001). Significantly higher proportions of those with a lower education level (38%) were able to stop using MS compared to respondents with a higher education level.
Our study provides important information on the pattern of MS use, its effects and its potential to cause addiction, as there has been growing interest in MS as evidenced by the number of advertisements for its sale on the Internet. Future study is required to explore its psychological and social impact on users.
Recently, the abuse of ketum, an indigenous psychoactive plant, has received a lot of attention in Malaysia. To help national law enforcement agencies control its abuse, the laboratory of the Forensic Division has developed a procedure for its positive identification. Botanical identification may not be practical or conclusive, owing to the wide range of ketum materials available on the market, including dry macerated leaves, powdered leaves and drinks. In order to confirm that a substance is, in fact, ketum or that a preparation is derived from ketum, gas chromatography-mass spectrometry is used to definitively identify the presence of the psychoactive principle mnitragynine.
The effects of pure alkaloid, mitragynine and a methanolic extract of kratom leaves were investigated on neuromuscular junction and compound nerve action potential.
Wistar rats were killed by cervical dislocation and decapitated. The phrenic nerve-hemidiaphragms, hemidiaphragms and sciatic nerve were isolated.
Kratom methanolic extract present at 0.1-1 mg/mL and mitragynine (0.0156 mg/mL) decreased the muscle twitch on the isolated phrenic nerve-hemidiaphragm and hemidiaphragm preparation. Muscle relaxation caused by kratom extract (1 mg/mL) was greater than the effect of mitragynine. Pancuronium and succinylcholine potentiated the effect of kratom extract. It also had a direct relaxation effect on the hemidiaphragm muscle. The muscle relaxation caused by kratom extract was not antagonized by neostigmine, tetraethylammonium and calcium chloride. High concentrations of kratom extract (10-40 mg/mL) and mitragynine (2 mg/mL) blocked the nerve conduction, amplitude and duration of compound nerve action potential.
The mechanism of action of kratom extract might not act as a competitive antagonist of acetylcholine yet its dominant effect was at the neuromuscular junction and not at the skeletal muscle or somatic nerve.
Kratom is indigenous to Thailand. Market gardeners, peasants and labourers often become addicted to kratom leaf use. In certain respects, kratom addiction resembles addiction to a drug with narcotic properties, except that long term kratom addicts develop a dark skin, particularly on the cheeks. The age of onset is apparently later than in heroin addiction, and females are rare amongst those who use the substance. There were 5 cases of kratom addiction revealing psychotic symptoms; these had been seen by the author in the last yr (1974) in the outpatient department. Initially, 3 cases were suspected of having kratom psychosis of the basis of their history of addiction and their general appearance and on psychiatric examination. The measure chosen by lar to control kratom addiction by banning the cultivation of the tree has not been found to be effective, since it is a local law It is hoped that drug education for the rural youth in areas where kratom can be grown will be a more effective step towards its control.
Kratom (Mitragynia speciosa korth) is recognized increasingly as a remedy for opioid withdrawal by individuals who self-treat chronic pain.
A patient who had abruptly ceased injection hydromorphone abuse self-managed opioid withdrawal and chronic pain using kratom. After co-administering the herb with modafinil he experienced a tonic-clonic seizure, but he reported only modest abstinence once kratom administration stopped. We confirmed the identity of the plant matter he ingested as kratom and identified no contaminants or adulterants. We also conducted high-throughput molecular screening and the binding affinity at mu, delta and kappa receptors of mitragynine.
We report the self-treatment of chronic pain and opioid withdrawal with kratom. The predominant alkaloid of kratom, mitragynine, binds mu- and kappa-opioid receptors, but has additional receptor affinities that might augment its effectiveness at mitigating opioid withdrawal. The natural history of kratom use, including its clinical pharmacology and toxicology, are poorly understood.
A high-perfor-mance liquid chromatographic method for determination of active substances in kratom (Mitragyna speciosa Korth.) cocktail”; Asnang-kornchai
- S Chittarakarn
Chittarakarn, S. et al. 2008. “A high-perfor-mance liquid chromatographic method for determination of active substances in kratom (Mitragyna speciosa Korth.) cocktail”; Asnang-kornchai, S. & Siriwong, A. (eds.) 2005. Kratom Plant in Thai Society: Culture, Behavior, Health, Science, Laws.