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A study of kratom eaters in Thailand
Abstract
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.
... At low doses, it shows stimulant activity and at high doses, it acts like opioid property, giving sedation (Warner et al. 2016). It increases stamina and elevates mood along with the reduction of anxiety (Suwanlert 1975). In the earlier generation of Malaysia (Malay peninsula), opium use was quite common. ...
... In Thailand, kratom is reported to be used as an alternative to heroin with a view to overcome the heroin dependence as well as to mitigate the associated withdrawal symptoms (Tanguay 2011). Some regular users consume M. speciosa leaves alone or in combination with alcohol to increase sexual stimulation and duration of sexual intercourse with the belief that it possesses aphrodisiac properties (Suwanlert 1975). People use M. speciosa leaves to treat muscle and joint pain post hard work (Singh et al. 2017). ...
... People use M. speciosa leaves to treat muscle and joint pain post hard work (Singh et al. 2017). It is an appetite suppressor as well as it is used as a wound poultice (Burkill and Haniff 1930;Suwanlert 1975) and deworming agent (Domnic et al. 2022). In traditional medicine, it is also believed to be used in diarrhoea and intestinal infections (Burkill 1935;Assanangkornchai et al. 2007). ...
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.
... The major mental health drawback of kratom use as a therapeutic agent is its addictive potential, characterized by its association with development of withdrawal symptoms and craving on abstinence, tolerance and cross-tolerance, and the risk of developing kratomrelated substance use disorder (16,17,19,20,22,29,(32)(33)(34)(35)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58). ...
... Despite this, Suwanlert (1975) explained that five out of 30 kratom respondents exhibited psychotic symptoms (altered consciousness, delusion, and hallucination). These psychotic respondents were also complicated by comorbid use of other illicit substances (amphetamine, alcohol, and heroin) and a history of schizophrenia (16). ...
... Despite this, Suwanlert (1975) explained that five out of 30 kratom respondents exhibited psychotic symptoms (altered consciousness, delusion, and hallucination). These psychotic respondents were also complicated by comorbid use of other illicit substances (amphetamine, alcohol, and heroin) and a history of schizophrenia (16). In a cross-sectional study with a larger sample size of regular kratom users (n = 150), only 4% of the participants experienced psychotic symptoms, such as positive symptoms and thought alienation. ...
Aims: This review aimed to comprehensively examine kratom’s therapeutic potential for treatment of mental health-related issues as well as any related benefits and risks. Design: Systematic review. Data sources: Google Scholar, Web of Science, PubMed, Scopus, PsycINFO, EMBASE, Cochrane Library, and Medline. Review methods: Three authors carried out electronic search of articles published between 1950 to September 2022 through major databases for a duration of three months (from July to September 2022). Each author independently screened the literature for inclusion and exclusion criteria, the findings were then compared, discrepancies between authors were resolved, and the final selection of articles were reviewed. Results: A total of 46 articles were included in this review. A total of three in vitro and animal studies and five cross-sectional online surveys reported the therapeutic potential of kratom in opioid replacement therapy. In addition, a total of two animal studies and three cross-sectional online surveys highlighted the role of kratom as a potential antidepressant and anxiolytic. Contrastingly, two animal studies, 11 studies in human subjects, and 16 case reports documented the risk of kratom dependence, cravings, tolerance, and kratom-related substance use disorder as the major safety concern of implementing kratom use as a therapeutic agent. Conclusion and impact: In the absence of human clinical trial, coupled with various considerable adverse events of kratom (not limited to psychological side effects), evidence to support kratom as potential therapeutic use remains inconclusive.
... Havil (Figure 1), a tropical tree that may reach heights of 4 to 16 m and is found in both Asia and Africa [13]. In various regions of Southeast Asia, manual laborers have traditionally made tea or chewed on the tree's chopped fresh or dried leaves to reduce weariness and boost productivity [38]. Kratom compounds have also been used for thousands of years in ceremonial social rites and to cure a wide range of diseases, including opium addiction in Malaya and morphine dependence in Thailand [39]. ...
... It has been demonstrated experimentally that low to moderate dosages (1 to 5 g) provide modest stimulant effects to aid employees in overcoming weariness [9]. High dosages (>15 g) are associated with reports of anxiety, irritation, and increased aggression, which have been linked to several unusual consequences [9,38,51]. For some users, the kratom withdrawal effect is quite unpleasant, making it difficult to maintain abstinence, as similar to opioid withdrawal. ...
... There was also evidence that 7-HMG, a minor constituent of kratom, was 46 times more potent as an analgesic than mitragynine in another study [122]. In humans, it exerts sedative and analgesic effects at higher doses and stimulant effects at low doses [38]. Due to this characteristic of the plant, drug addicts have been highly tempted to abuse it [128]. ...
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.
... Ein möglicher Grund für den steigenden Kratomeinsatz könnte einerseits das zunehmende Interesse der Betroffenen an alternativen Therapien für chronische medizinische Probleme sein (Eisenberg et al., 1993, Eisenberg et al., 1998, andererseits aber auch die Unzufriedenheit der Patienten hinsichtlich der aktuell gängigen chronischen Schmerzbehandlungen , Joranson et al., 2002 (Singh et al., 2016, Ward et al., 2011, Swogger et al., 2015. (Suwanlert, 1975 (Henningfield et al., 2018, Swogger et al., 2015, Singh et al., 2014. Unter diesem Gesichtspunkt könnte man dem Kratom-Konsum mehr eine schadensbegrenzende als eine missbräuchliche Wirkung zuschreiben (Swogger und Walsh, 2018, Hassan et al., 2013. ...
... Zusammengefasst besitzt Kratom nachweislich das Potential Abhängigkeiten zu erzeugen, welche unter bestimmten Umständen zu einer ernsthaften Sucht heranwachsen können (Singh et al., 2014). So berichten einige Arbeiten von entstandener Abhängigkeit und einer Toleranzentwicklung gegenüber dem Produkt bei chronischem Konsum (Singh et al., 2016, Suwanlert, 1975, Henningfield et al., 2018, Yusoff et al., 2016. (Suwanlert, 1975), wobei die relativ leichte Rhinorrhoe laut Erfahrungsberichten die Hauptbeschwerde darstellt . ...
... So berichten einige Arbeiten von entstandener Abhängigkeit und einer Toleranzentwicklung gegenüber dem Produkt bei chronischem Konsum (Singh et al., 2016, Suwanlert, 1975, Henningfield et al., 2018, Yusoff et al., 2016. (Suwanlert, 1975), wobei die relativ leichte Rhinorrhoe laut Erfahrungsberichten die Hauptbeschwerde darstellt . ...
1. Zusammenfassung 1.1. Hintergrund und Ziele Alkoholismus ist eine schwerwiegende, in Deutschland und weltweit verbreitete Erkrankung mit physischen, psychischen und sozialen Symptomen, welche die Lebensqualität und Lebenserwartung der Betroffenen deutlich reduziert. Aktuelle Therapiekonzepte erfordern ein hohes Maß an Mitarbeit der Patienten, sind langwierig und erzielen oft auf Dauer nicht ihren gewünschten Erfolg. Zum jetzigen Zeitpunkt besitzen in Deutschland nur drei Medikamente ihre Zulassung als Mittel der pharmakologischen Therapie bei Alkoholabhängigkeit. Zwei dieser Pharmaka entfalten ihre Wirkung im Bereich des opioidergen Systems des Körpers. Auch Mitragynin, eines der Hauptalkaloide der Blätter des Kratombaumes, wirkt, wie in zahlreichen Studien nachgewiesen, unter anderem auf Opioidrezeptoren. Vor diesem Hintergrund befasst sich die vorliegende Arbeit nun mit der Frage, wie sich Mitragynin auf den Alkoholkonsum einer Gruppe männlicher Mäuse auswirkt und ob ein möglicher rückfallprophylaktischer Effekt nachgewiesen werden kann. 1.2. Methoden Für das Experiment wurden 14 männliche C57/BL6 Mäuse über einen Versuchszeitraum von 105 Tagen gemeinsam in einem IntelliCage® der Firma TSE Systems GmbH gehalten. An zwei Stunden pro Tag hatten sie begrenzt Zugang zu Alkohol in langsam ansteigender Konzentration (3 Vol.-%, 6 Vol.-%, 12 Vol.-% jeweils vier Tage, bis 20 Vol.-% 29 Tage), in den restlichen 22 Stunden erhielten sie Wasser ad libitum. Nach einer Alkoholtrinketablierung von 28 Tagen erfolgte jeweils für drei Tage die einmal tägliche Behandlung mittels intraperitonealer (i.p.) Injektion der Tiere, geteilt in zwei Gruppen mit einer 5 mg/kg Körpergewicht Mitragyninlösung einerseits und einem Vehikel (Kontrolllösung) andererseits. Die Injektionszeitpunkte wurden so gewählt, dass die Anwendungen einmal während des akuten Trinkens ohne Entzugserfahrung und einmal während des Entzugs vor dem Wiedereinsetzten des Trinkens stattfanden, um festzustellen, ob Mitragynin den Alkoholkonsum in den jeweiligen Paradigmen reduzieren kann. Während der Behandlungsdauer wurden das Körpergewicht [g], der Alkoholkonsum [g/kg/2 Stunden] und der Wasserkonsum [ml/kg/22 Stunden] der Tiere pro Tag gemessen, ausgewertet und dokumentiert. 1.3. Ergebnisse und Beobachtungen Die Resultate des Experiments zeigen, dass bei der Anwendung von Mitragynin während des akuten Trinkens eine hochsignifikante Reduktion des Alkoholkonsums im Vergleich zur Kontrollgruppe zu verzeichnen ist, was auf einen trinkmengenreduzierenden Effekt von Mitragynin hinweist. Der Wasserkonsum während der Behandlungszeit zeigte keine erwähnenswerten Unterschiede, rein in den Postbehandlungstagen stieg der Wasserkonsum in der Mitragynin-Gruppe signifikant in einem nicht besorgniserregenden Rahmen an. Kein signifikanter Unterschied im Alkoholkonsum konnte hingegen bei der Anwendung von Mitragynin während des Entzugs vor dem Wiedereinsetzen des Trinkens nachgewiesen werden. Auch der Wasserkonsum blieb in diesem Paradigma im Vergleich zur Kontroll-Gruppe unverändert. Diese Ergebnisse weisen darauf hin, dass Mitragynin wohl keine rückfallprophylaktischen Effekte erzielen kann. 1.4. Schlussfolgerungen und Diskussion Die Beobachtungen dieser Studie bekräftigen die Hypothese, dass der Einsatz von Mitragynin den Alkoholkonsum im akuten Stadium der Alkoholabhängigkeit im Mausmodell reduzieren kann. Somit wäre ein therapeutischer Einsatz bei Patienten ohne Entzugserfahrungen zur Reduktion der Trinkmenge denkbar. Zuvor bedarf es jedoch noch einiger tierexperimenteller und klinischer Studien, um bleibende offene Fragen über den genauen Wirkmechanismus von Mitragynin an den verschiedenen Rezeptoren zu beantworten.
... 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). ...
... Kratom, as discussed before, has opioid properties, thus might bear the risk of addiction. Suwanlert (1975) also reported that chronic use of Kratom can trigger withdrawal symptoms in its user. Physiological withdrawal symptoms encountered include headache, nausea, vomiting, fever, decreased appetite, tremor, muscle spasms and pain, sleeping difficulty, watery eyes/nose, hot flashes, and diarrhea. ...
... The toxicology of Kratom has been studied and discussed extensively. While common side effects from kratom tea ingestion like dry mouth, constipation, nausea, sleep disorder, and diuretic (Suwanlert, 1975;Cinosi et al., 2015) can seem harmless, a more extensive study can give us valuable information on the toxicological properties of Kratom. ...
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
... ISSN (Online): 2630-0087 Research Article kratom can treat and alleviate the symptoms of diabetes and relieve body aches. Traditional healers have used the bark and leaves of kratom to treat diarrhea, abdominal pain, bloody diarrhea, stomach ailments, diabetes, high blood pressure, skin diseases, and purulent wounds (Gordon and Lowy, 2008;Suwanlert, 1975;Weese, 2010), but research on kratom in Thailand is scarce, compared to research in Malaysia and Indonesia (Parthasarathy et al., 2009;Salim et al., 2021). ...
... The Narcotics Affairs Section (NAS) at the U.S. Embassy in Thailand, Office of the Narcotics Control Board, Ministry of Justice, encouraged the publication of a book "kratom leaves in Thai society". Part of the text shows the percentage of diseases for which southern healers used kratom for treatment of issues such as diarrhea and purulent wounds (Suwanlert, 1975). The present study evaluates the antibacterial activity of red vein kratom leaves crude extracts and mitragynine. ...
The crude extracts of red vein kratom leaves (hexane, dichloromethane, ethyl acetate, ethanol, and 50% acetic acid) and mitragynine were tested for antibacterial activity against gram-positive Staphylococcus aureus and gram-negative Escherichia coli using the disk diffusion method. The minimum inhibitory concentration (MIC) values against S. aureus and E. coli were determined. The acetic acid crude extract was effective against both S. aureus and E. coli with an inhibition zone of 5.52±0.44 and 4.65±1.02 mm, at a minimum concentration of 6 and 9 mg/mL, respectively. Mitragynine was active against S. aureus with an inhibition zone of 4.35±0.68 mm and a MIC of 6 mg/mL.
... [5] In local folk medicine, Kratom leaf has been utilized as single herb and ingredient in remedy for various reasons, such as treating diarrhea or dysentery, muscle pain, hemorrhoids, acting as an antipsychotic, serving as a substitute medication for opium addicts, and even enhancing labor performance. [7] Kratom has been investigated for its various pharmacological properties, including analgesic activity [8][9] , anti-oxidant [10] , anti-diabetes [11][12] , anti-inflammation [13] anti-depression [14][15] , antibacterial [10] , antiproliferation activity [16] and anti-Alzheimer's desease [17] . Innok and colleagues demonstrated the molecular docking and in vitro experiments on mitragynine and Kratom extract to explore AChE inhibition. ...
... Kratom has a long and rich history of use in Thailand particularly as an ingredient in TTM remedies, but it has never been utilized as single herb in TTM practice. However, local folk medicine, especially in southern Thailand, has a tradition of chewing Kratom leaves for variety of reasons, including the treatment of diabetes, hypertension, and even to boost work performance [7] . The objective of this study was to investigate the enzymatic-based biological activities related to anti-diabetes, anti-hypertension, and anti-Alzheimer's disease based on both traditional medicine and the folk usage of Kratom leaves, in order to support the legislative intention of unlocking its use as an herbal or traditional medicine. ...
Introduction and Objective: Kratom leaves (Mitragyna speciosa Korth) have been an integral part of traditional Thai medicine and local folk medicine for a long time. In Thailand, it has recently been legalized for use as a medicinal plant or traditional Thai medicine. Consequently, kratom has gained popularity as a medicinal plant based on people’s beliefs. This study aimed to investigate the enzymatic-based biological activities of kratom extracts, specifically their anti-diabetic, anti-hypertensive, and anti-Alzheimer’s disease properties, in order to provide scientific information for further development of kratom for medical use.
Methods: The kratom extracts used in this study were 95%, 70%, and 50% ethanolic extracts obtained from maceration, as well as an aqueous extract obtained from decoction method. All extracts were evaluated for inhibitory activities on alpha-glucosidase and alpha-amylase for anti-diabetes while its effect on angiotensin-I converting enzyme was examined for anti-hypertension. For the anti-Alzheimer’s disease property, the inhibitory effects on acetylcholinesterase and butyrylcholinesterase were investigated.
Results: The study found that kratom extracts exhibited inhibitory effects on acetylcholinesterase, butyryl-cholinesterase, and alpha-glucosidase enzyme. The 95% ethanolic extract exhibited the highest activity on butyr-ylcholinesterase and acetylcholinesterase, with the half inhibitory concentration (IC50) values of 64.40 ± 16.74 μg/mL and 127.99 ± 6.15 μg/mL, respectively. The 70% and 50% ethanolic extracts demonstrated comparable effects on alpha-glucosidase enzyme, with IC50 values of 382.64 ± 16.18 μg/mL and 409.43 ± 19.14 μg/mL, respectively.However, all extracts were inactive on angiotensin-I converting enzyme and alpha-amylase enzyme. The content of mitragynine in the 95%, 70%, 50% ethanolic extracts and the aqueous extracts were 54.00 ± 1.17, 35.14 ± 0.64, 25.05 ± 0.05, and 18.08 ± 0.30 mg/g, respectively.Discussion:Kratom extracts showed the most potential as butyrylcholinesterase and acetylcholinesterase inhibitors, and exhibited moderate activity in inhibiting alpha-glucosidase. The 95% ethanolic extract exhibited the highest mitragynine content, which was correlated with its ability to inhibit acetylcholinesterase and butyryl-cholinesterase enzymes. This study was limited to explore only the in vitro enzymatic-based assays which require additional in vitro and in vivo assay models to conclude the possibility of using kratom as a medicine for patients or as dietary supplement.
Conclusion and Recommendation: The findings of this study suggested the inhibitory effects of kratomextracts on acetylcholinesterase, butyrylcholinesterase and alpha-glucosidase. Moreover, further in vitro and in vivo assay models as well as clinical trials are necessary to confirm its potential for development as a traditional medicine, or dietary supplement.Key words:kratom, Mitragyna speciosa, Alzheimer, alpha-glucosidase, butyrylcholinesterase
... 48 The study failed to adequately address other areas, such as outcome assessment, internal validity, analysis, precision, and external validity. After evaluating the studies by Suwanlert, 43 Prat et al., 44 Cutlip et al., 45 Nunez et al., 46 Garrels et al. 47 and Khalil et al., 48 we found that each of them had strengths and weaknesses in various areas, including selection, ascertainment, causality, outcome assessment, internal validity, analysis, precision, and external validity. These included studies show varying levels of adequacy in key criteria such as selection, causality, and outcome assessment, among others. ...
... Prior published literature has shown an association between kratom use and the exacerbation of psychotic symptoms. Suwanlert 43 first reported this association, 43 later which was supported by several other researchers. [44][45][46]50 In addition, several published case reports have noted the worsening of psychiatric symptoms in patients with preexisting conditions following kratom use. ...
... Kratom (Mitragyna speciosa Korth) is a tropical tree belonging to the coffee plant family Rubiaceae and is native to peninsular Thailand, Malaysia, Indonesia, and other Southeast Asian countries [1]. Kratoms have been a culturally significant plant in Thai society since the nineteenth century [2]. For centuries, kratom has been traditionally used in different parts of Thailand under various local names such as Thom, E-Thang, Ketum, Kratum-Koke, and Maeng Da Leaf [2,3]. ...
... Kratoms have been a culturally significant plant in Thai society since the nineteenth century [2]. For centuries, kratom has been traditionally used in different parts of Thailand under various local names such as Thom, E-Thang, Ketum, Kratum-Koke, and Maeng Da Leaf [2,3]. Among traditional preparations, fresh kratom leaves are often chewed and boiled to make a decoction, while dried leaves can be smoked, brewed as tea, or ingested as an herbal beverage by adding honey and lemon [3]. ...
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.
... Among the top publications, the oldest publication dates back to 1975, titled "Study of kratom eaters in Thailand" by Suwanlert (1975). This paper generally presents the muciferous scenario of Kratom usage as a cooking ingredient in medicine by the Thais, specifically its usage amongst villagers. ...
... This paper also shows us that the academic concentration on Kratom in the SEA region is quite old. Even being a classic academic paper, Suwanlert's (1975) paper is ranked fourth in the top document list that we found. This paper, titled "Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds," published in 2010 and authored by Dresen et al. (2010) is the most cited. ...
Kratom has caught the attention of governments, policymakers, and academicians due to its unique characteristics. This paper explores the scholarly works related to the different aspects of Kratom to elucidate its research progress and identify future research agendas. We reviewed existing publications on Kratom using a bibliometric methodology. By analyzing 431 scientific publications, we identified publication sources, document analysis, countries analysis, and research keywords, which helped us understand the research locus on Kratom. After reviewing the publications, we discovered significant disagreements in categorizing and defining Kratom amongst authors based on their nationalities. We also showed the knowledge structure of existing publications via thematic analysis, illustrating that the studies focused on the opioid nature of Kratom. Also, drug abuse-related issues evolved as the motor theme of research, while other aspects are prevalent as niche or emerging research themes. This paper contributes to the literature by providing a broad idea of existing literature and offering a comprehensive outlook on Kratom, which could be helpful for policy formulation in the future.
... Kratom (Mitragyna speciosa) is in a small Afro-Asian genus characterized by mitriform stipules at the base of the leaf and globular flowering heads (Razafimandimbison and Bremer, 2002). The species itself is a tropical, facultative deciduous, small to medium sized (4-16 m) tree, native to peninsular Thailand, Malaysia, and other countries in tropical Southeast Asia (Eisenman, 2014) and has also been reported in Vietnam and Myanmar (Suwanlert, 1975). Its leaves contain secondary metabolites (SMs) and are consumed either soaked in tea or chewed by natives and laborers for its euphoric effects at low doses (Babu et al., 2008). ...
... Its leaves contain secondary metabolites (SMs) and are consumed either soaked in tea or chewed by natives and laborers for its euphoric effects at low doses (Babu et al., 2008). Kratom has long been used in traditional medicine in Southeast Asia to treat diarrhea, fatigue, cough, hypertension, and as an analgesic (Suwanlert, 1975;Cinosi et al., 2015;Grundmann, 2017). ...
We analyzed the content of mitragynine (MG) found in kratom leaves (Mitragyna speciosa) and the influence of different environmental conditions (air and soil variables) on the yield in various regions of Thailand. The content of MG in kratom leaves ranged from 7.5 – 26.6 mg g⁻¹ of dry leaf weight. Canonical correspondence analysis showed that the most significant environmental variables affecting the MG content among the various regions were light intensity, relative humidity, soil volumetric water content (VW), soil pH, and calcium. This study is a first step towards providing information about environmental conditions suitable to maximize the quality and quantity of bioactive alkaloids in kratom. Future studies should focus on leaf collection and the post-harvest processes in order to assure the desired alkaloidal content in finished products, when produced under suitable environmental conditions identified in this study.
... Mitragyna speciosa, commonly known as kratom, is a tropical small to medium size (4-16 m) tree indigenous to wetland forests of Southeast Asia. Historically, kratom was used in Thailand, Malaysia, and Indonesia to serve as a mild herbal stimulant, pain reliever, and to treat diarrhea and opium addiction [1][2][3]. Given its historical use as an analgesic and a medicine to mitigate opioid withdrawal symptoms, research on kratom cultivation and use is warranted. ...
... Given its historical use as an analgesic and a medicine to mitigate opioid withdrawal symptoms, research on kratom cultivation and use is warranted. In Southeast Asia, kratom leaves are harvested and consumed fresh by chewing or steeping in water to make tea [3]. In the Western hemisphere where fresh kratom is unavailable, kratom is sold in the form of dried and ground powder or as a concentrated liquid extract for easier transportation and consumption [4]. ...
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.
... Despite its reported benefits, long-term and chronic (high dose) kratom consumption can induce the development of tolerance and withdrawal symptoms during discontinuation ( [18][19][20][21]. It is also documented that people may develop dependence from chronic kratom use (22,23), which is consistent with findings of a study of individuals who reported using kratom to address dependence on other substances and end up experiencing difficulty ceasing kratom use (24). ...
... Symptoms of kratom dependence have been documented in humans (22,(43)(44)(45). Here, we found 45.3% experienced negative effects similar to various degrees of opioid withdrawal symptoms. ...
Background:
Kratom (Mitragyna speciosa Korth.) use outside of Southeast Asia has increased over the past decade.
Objectives:
This investigation clarifies kratom's role in perceived well-being, overall health, and temporal correlation with drug use to understand kratom's role in the self-treatment of substance use disorders (SUDs).
Methods:
Between July 2019 and July 2020 an anonymous, cross-sectional, online survey was taken by 7,381 people who use kratom (PWUK) recruited through social media and other online resources. This included an assessment of (a) the relationship between self-reported overall health, concomitant use of drugs of misuse, and demographics; (b) the perceived effectiveness of kratom in self-treating diagnosed health conditions or symptoms; (c) the profile of PWUK primarily for drug dependence, pain, and mood or mental health conditions based on demographics.
Results:
A total of 5,152 valid responses (45.9% females/53.7% males) were collected. Kratom was primarily used for self-treating pain (73.0%) and improving emotional or mental health conditions (42.2%) without clinical supervision. Those with a SUD (synthetic opioids, methadone, benzodiazepines, or heroin) used kratom after discontinuing illicit or other drugs (94.8%). The primary substances taken before or concomitantly with kratom were cannabis, cannabidiol, benzodiazepines, or kava. PWUKs report a dose-dependent benefit for alleviating pain and relieving negative moods. Adverse effects were primarily gastrointestinal, typically at high (>5 g/dose) and frequent (>22 doses/week) dosing.
Conclusions:
Kratom was primarily used as a harm-reduction agent for SUDs and self-treatment of chronic conditions. Healthcare professionals need better information about kratom, its potential adverse effects, and clinically significant drug interactions.
... Havil. is a Southeast Asian plant with a rich history of medicinal use dating back to the 19th century ( Hassan et al. , 2013;Singh et al. , 2017) . Traditionally, Kratom leaves are believed to treat various ailments and enhance physical strength, making them popular among manual laborers ( Nakaphan et al. , 2016;Suwanlert, 1975) . Recent pharmacological studies have unveiled a diverse array of bioactive compounds in Kratom, with mitragynine as the primary alkaloid and 7-hydroxymitragynine demonstrating superior analgesic properties (Prevete et al., 2023). ...
Kratom, Mitragyna speciosa (Korth.) Havil. is a medicinal plant native to Southeast Asia that is renowned for its therapeutic properties and potential in treating various ailments. Despite its significance, the cultivation and propagation of Kratom have been limited. The purpose of the present study was to develop a cost-effective micropropagation protocol for Kratom by investigating the disinfection efficiency and cost-effectiveness of various chemical disinfectants, optimizing plant growth regulator concentrations, and assessing cost-effective media sterilization methods. The results demonstrated that double disinfection with commercial bleach at 20% and 15% for 5 min each was the most cost-effective treatment for surface disinfection of Kratom seeds, achieving a high disinfection rate (96.67±2.89%) and survival rate (73.33±2.89%) at a relatively low cost (1.46 baht per experiment) compared to mercuric chloride (HgCl2) treatments. The evaluation of benzyladenine (BA) and naphthaleneacetic acid (NAA) effects on in vitro growth revealed that the control treatment (MS (Murashige and Skoog medium) without growth regulators) exhibited the best overall growth performance. Among the low-cost disinfectants tested for the culture medium, while autoclaving offers superior disinfection efficacy, commercial bleach at 2 ml/l emerged as the most cost-effective option, especially for resource-limited operations. The final choice, however, should align with specific operational requirements, including scale, resources, and the need for complete disinfection. The successful establishment of a cost-effective micropropagation protocol using low-cost chemical disinfectants and optimized plant growth regulator concentrations can significantly reduce the production costs associated with tissue culture techniques, making the micropropagation of Kratom more economically viable and accessible for large-scale production. The findings from this research provide insights into cost-effective micropropagation methods for Kratom, which will prove valuable for future studies and applications in the field.
... Historical claims of medicinal or pharmacological effects of chewing fresh leaves of kratom tree (Mitragyna speciosa) native to Southeast Asia [1][2][3], supplemented by narrative accounts of potential health benefits of products derived from kratom and consumed in the United States and other countries in the West [4] garnered an increasing interest among researchers, clinicians, and the public in recent years. Although there is a growing demand for kratom-derived products among the United States consumers, there is also a paucity of rigorously collected scientific data on human pharmacological safety profile of kratom phytochemicals and very limited scientific data on their dose-related effects in humans [5]. ...
Purpose of review
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.
Recent findings
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.
Summary
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.
... Pain management, opioid withdrawal, and fatigue are among Kratom's traditional uses. 1,14 However, liver toxicity, seizures, and death have been reported. 15,16 Furthermore, Kratom may potentiate the toxicity of co-administered medications through modulation of cytochrome P450, P-glycoprotein, and uridine diphosphate glucuronosyltransferase enzymes. ...
Kratom (Mitragyna speciosa) is used as a stimulant, an opioid-like analgesic, and a sedative. However, Kratom consumption has profound effects, such as seizures, withdrawal, hallucinations, coma, and cardiac or respiratory arrest. We tested Kratom's effects on pentylenetetrazole-induced seizures in adult zebrafish (D rerio) using hydroethanolic Kratom extracts. Kratom extracts have pro-convulsant effects at low concentrations (10-4-10-1 mg/mL), while sedation occurs at higher concentrations. In the open-field test, Kratom has no anxiolytic effects; however, "social" behavior was lost at high concentrations (1.0 mg/mL). Our results confirm the possible proconvulsant role of Kratom while questioning its anxiolytic effects.
... 8,9 We have recently used imaging mass spectrometry to map the brain spatial distributions of alkaloids derived from Mitragyna speciosa, a species of plant native to Southeast Asia commonly known as kratom and used to reduce fatigue, treat pain, and treat opioid withdrawal symptoms. [10][11][12][13] Although it is known that the alkaloid components of kratom are the major contributors to its therapeutic effects, the specific alkaloids and mechanisms of action remain unclear. Kratom is currently not approved by the U.S. Food and Drug Administration (FDA) because of these potential health risks and the unknown effects on brain chemistry, highlighting the need for increased study by imaging technologies. ...
Multi-modal imaging analyses of dosed tissue samples can provide more comprehensive insight into the effects of a therapeutically active compound on a target tissue compared to single-modal imaging. For example, simultaneous spatial mapping of pharmaceutical compounds and endogenous macromolecule receptors is difficult to achieve in a single imaging experiment. Herein, we present a multi-modal workflow combining imaging mass spectrometry with immunohistochemistry (IHC) fluorescence imaging and brightfield microscopy imaging. Imaging mass spectrometry enables direct mapping of pharmaceutical compounds and metabolites, IHC fluorescence imaging can visualize large proteins, and brightfield microscopy imaging provides tissue morphology information. Single-cell resolution images are generally difficult to acquire using imaging mass spectrometry, but are readily acquired with IHC fluorescence and brightfield microscopy imaging. Spatial sharpening of mass spectrometry images would thus allow for higher fidelity co-registration with higher resolution microscopy images. Imaging mass spectrometry spatial resolution can be predicted to a finer value via a computational image fusion workflow, which models the relationship between the intensity values in the mass spectrometry image and the features of a high spatial resolution microscopy image. As a proof of concept, our multi-modal workflow was applied to brain tissue extracted from a Sprague Dawley rat dosed with a kratom alkaloid, corynantheidine. Four candidate mathematical models including linear regression, partial least squares regression (PLS), random forest regression, and two-dimensional convolutional neural network (2-D CNN), were tested. The random forest and 2-D CNN models most accurately predicted the intensity values at each pixel as well as the overall patterns of the mass spectrometry images, while also providing the best spatial resolution enhancements. Herein, image fusion enabled predicted mass spectrometry images of corynantheidine, GABA, and glutamine to approximately 2.5 μm spatial resolutions, a significant improvement compared to the original images acquired at 25 μm spatial resolution. The predicted mass spectrometry images were then co-registered with an H&E image and IHC fluorescence image of the μ-opioid receptor to assess co-localization of corynantheidine with brain cells. Our study also provides insight into the different evaluation parameters to consider when utilizing image fusion for biological applications.
... Kratom has long been used in Southeast Asia to treat pain and ease the symptoms of opium withdrawal (136,137,138,139). People in the West are using kratom more frequently to manage their own pain or to help them stop using opioid medications like heroin and prescription painkillers (140,141). ...
P-block elements have a long and varied history from ancient times. In pharmacological therapy, P-block elements might have some advantages over purely organic compounds. Such as dental problems, drug delivery, eye, respiratory, and gastrointestinal diseases. These elements are also used as anti-cancerous drugs, anti-ulcerative drugs, anti-microbial, anti-bacterial, anti-fungal agents, etc. For example, antimony (anti-protozoal), bismuth (anti-ulcer), gold (anti-arthritic), iron (anti-malarial), platinum (anti-cancer), and silver (antimicrobial) compounds in the treatment of various diseases. This review is the collection of pharmacological and therapeutic advantages of P-block elements. Many different transition metal and main group element compounds have been studied for their potential anti-tumor action. Although P-block elements are widely used to treat a wide range of illnesses, few of them have been scientifically screened out. Even though research into the potency of p-block elements has advanced tremendously, efforts to find newer therapeutic candidates continue. Therefore, research into the untapped potential of P-block elements should be done.
... The effects of kratom have been associated with the plant strain, which is visually characterized based on vein color, including white, green, or red (Suwanlert, 1975;Hartley et al., 2022). Vein color changes as the plant ages, from white at the young stage to green and finally to red after maturation (Ngernsaengsaruay et al., 2022). ...
Kratom is a botanical natural product belonging to the coffee family, with stimulant effects at low doses and opioid-like effects at higher doses. During the last two decades, kratom has been purported as a safer alternative to pharmaceutical and illicit drugs to self-manage pain and opioid withdrawal symptoms. Kratom alkaloids, typically mitragynine, have been detected in biological samples from overdose deaths. These deaths are often observed in combination with other drugs and are suspected to result from polyintoxications. This review focuses on the potential for kratom to precipitate pharmacokinetic interactions with object drugs involved in these reported polyintoxications. The legal status, chemistry, pharmacology, and toxicology are also summarized. The aggregate in vitro and clinical data identified kratom and select kratom alkaloids as modulators of cytochrome P450 (CYP) enzyme activity, notably as inhibitors of CYP2D6 and CYP3A, as well as P-glycoprotein-mediated efflux activity. These inhibitory effects could increase the systemic exposure to co-consumed object drugs, which may lead to adverse effects. Collectively, the evidence to date warrants further evaluation of potential kratom-drug interactions using an iterative approach involving additional mechanistic in vitro studies, well-designed clinical studies, and physiologically based pharmacokinetic modeling and simulation. This critical information is needed to fill knowledge gaps regarding the safe and effective use of kratom, thereby addressing ongoing public health concerns. Significance Statement The botanical kratom is increasingly used to self-manage pain and opioid withdrawal symptoms due to having opioid-like effects. The legal status, chemistry, pharmacology, toxicology, and drug interaction potential of kratom are reviewed. Kratom-associated polyintoxications and in vitro-in vivo extrapolations suggest that kratom can precipitate pharmacokinetic drug interactions by inhibiting CYP2D6, CYP3A, and P-gp. An iterative approach that includes clinical studies and PBPK modeling and simulation is recommended for further evaluation of the drug interaction potential of this increasingly popular botanical.
... or also known as "biak," "ketum," and "kratom," have been used for their opium-like and cocaine-like effects to relieve fatigue and enhance work productivity. In the colonial era, Malaya used the leaves to replace opium and is also used to wean addicts off in morphine addiction by the native of Thailand (27). However, due to its narcotic effects, some countries have banned the consumption of the Mitragyna speciosa (Korth.) ...
The effectiveness of antibiotics has declined significantly due to development of drug resistance. Consequently, it results in millions of deaths due to infectious diseases. Many studies have suggested that bioactive compounds produced by endophytes could be an alternative to discover new antimicrobial compounds. Endophytes are microorganisms that reside within the tissues of living plants that cause no apparent harm to the host. Fungal endophytes may biosynthesize the same or similar compounds as their host plant and other diverse bioactive compounds, which provide various pharmacological activities. Therefore, this study aimed to conduct literature search on the antimicrobial properties of the isolated compounds produced by fungal endophytes associated with Rubiaceae. Literature was conducted on secondary metabolites of endophytic fungi via four databases; EBSCOhost, Google Scholar, PubMed, and Scopus. A search filter was performed to include only research articles from 2007 to 2021. The search was restricted to publications in English only. Overall, 29 publications were selected for full-text evaluation and were included in the study. Results showed that sixteen antimicrobial metabolites were isolated from six fungal endophytes of ten different plant species were identified. These compounds were classified as alkaloid, phenol, coumarin, steroid, diterpene, and meroterpene.
... Mitragynine is the primary alkaloid derived from a plant (kratom) found in South-East Asia, where it is traditionally used to combat fatigue and improve work productivity (Cinosi et al., 2015;Suwanlert, 1975). In recent years, it has become particularly popular in the United States as a 'legal high' for its stimulant and/or opioid-like effects (Tobacyk et al., 2022). ...
The proliferation of new psychoactive substances (NPS) over recent years has made their surveillance complex. The analysis of raw municipal influent wastewater can allow a broader insight into community consumption patterns of NPS. This study examines data from an international wastewater surveillance program that collected and analysed influent wastewater samples from up to 47 sites in 16 countries between 2019 and 2022. Influent wastewater samples were collected over the New Year period and analysed using validated liquid chromatography – mass spectrometry methods. Over the three years, a total of 18 NPS were found in at least one site. Synthetic cathinones were the most found class followed by phenethylamines and designer benzodiazepines. Furthermore, two ketamine analogues, one plant based NPS (mitragynine) and methiopropamine were also quantified across the three years. This work demonstrates that NPS are used across different continents and countries with the use of some more evident in particular regions. For example, mitragynine has highest mass loads in sites in the United States, while eutylone and 3-methylmethcathinone increased considerably in New Zealand and in several European countries, respectively. Moreover, 2F-deschloroketamine, an analogue of ketamine, has emerged more recently and could be quantified in several sites, including one in China, where it is considered as one of the drugs of most concern. Finally, some NPS were detected in specific regions during the initial sampling campaigns and spread to additional sites by the third campaign. Hence, wastewater surveillance can provide an insight into temporal and spatial trends of NPS use.
... Before 2008, kratom use and physical dependence (i.e., withdrawal and/or tolerance) were, as best we can determine, documented only in SEA countries where kratom has a long history of medicinal and traditional uses [2][3][4][5][6]. Although few case reports have been published in SEA, there is now This article is part of the Topical Collection on Kratom documentation of kratom's being used in both SEA and the US by people seeking to self-manage substance use disorders (SUDs) involving opioids, stimulants, and alcohol and to self-treat fatigue [7][8][9][10]. ...
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.
... The fresh mature leaves of M. speciosa have been traditionally utilised for therapeutic purposes [13] by chewing or consumed as tea for stimulating effects that increase energy and work productivity [11,14,15]. It is also widely used in Southeast Asian countries as an aphrodisiac, to improve blood circulation, to endure physical fatigue, and to treat diarrhoea, fever, diabetes, chronic pain, and opiate withdrawal syndrome [12,[15][16][17][18][19]. The leaf extracts of M. speciosa have been reported to show various biological activities, including antibacterial, antioxidant [20], antimutagenic [21], antiinflammatory [22], antitussive [23], anaesthetic [24], antipsychotic [25], and antinociceptive [22,26,27] effects. ...
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.
... Upon binding to opioid receptors, the indole alkaloid activates G-protein-coupled receptors (GPCRs). Nevertheless, unlike conventional opioids, indole alkaloids do not initiate the β-arrestin pathway when they activate GPCRs (37). β-arrestin recruitment is responsible for the symptoms of opioid use, such as respiratory depression, sleepiness, and constipation (38,39). ...
Background: Mitragyna speciosa Korth or Kratom is widely used traditionally for its medicinal values. The major alkaloid content of kratom leaves is mitragynine, which binds to opioid receptors to give opioid-like effects. This study aimed to analyse the brain proteome of animals that displayed addictive behaviors.
Design and Methods: Six groups (n=6-8) of rats made up of negative control, positive control using morphine (10 mg/kg), and treatment groups at low (1mg/kg) and high doses of mitragynine (30 mg/kg) for 1 and 4 days. The rats' behaviors were evaluated and subsequently the rats' brains were harvested for proteomic analysis that was performed by using 2D gel electrophoresis and LC/MS/MS.
Results: The rats developed physical dependence only on day 4 following morphine and mitragynine (1 and 30mg/kg) treatments. Among the proteins that were up-regulated in treatment groups were four calcium-binding proteins, namely calretinin, F-actin, annexin A3 and beta-centractin.
Conclusions: Upregulation of calretinin acted as low Ca²⁺ buffering upon the blockage of Ca²⁺ ion channel by mitragynine in the brain, which subsequently caused a reduction of GABA released and inversely increased the dopamine secretions that contributed to dependence indicators.
... Proteomic analysis has been extensively used to study the aftermath of morphine administration [56] and morphine dependency [8,57,58]. A decrease expression of glycolytic enzymes such as phosphoglycerate mutase 1, pyruvate kinase, and glyceraldehyde-3-phosphate dehydrogenase indicates that prolonged morphine therapy impairs glucose metabolism [59]. ...
... Kratom is a tropical evergreen tree (Mitragyna speciosa) which has been used in herbal medicine in Southeast Asia since the nineteenth century for its stimulant effects. 1 Mitragynine and 7-hydroxymitragynine are the key compounds which could act on μ-opioid receptors. 2 Kratom has been used recreationally for alleviating pain, anxiety, depression, or opioid withdrawal. ...
Introduction:
Mitragyna speciosa (commonly known as kratom) has both opioid and stimulant-like effects. Recently, Thailand decriminalized the possession and sale of kratom which led people in many areas to seek income from the sale of kratom at a time of widespread unemployment due to COVID-19. Here, we report a patient with post-COVID syndrome who developed a mixed cholestatic-hepatocellular liver injury secondary to kratom.
Case presentation:
A 23-year-old Thai man was seen for an evaluation of fatigue and nausea which was soon followed by pruritus, dark urine and jaundice. The patient had no known underlying disease but had been treated with mild COVID-19 pneumonia in the past 2 months. He reported taking kratom recreationally for 2 weeks as a treatment for his post-COVID insomnia. Kratom was purchased from a friend and used in a homemade iced cocktail called "4 × 100" consisting of Coca-Cola, tea made from boiled kratom leaves, and diphenhydramine-containing cough syrup which has been popular in Southernmost provinces of Thailand. His lab workup showed his total bilirubin to be 10.6 mg/dL, aspartate aminotransferase was 642 U/L, and alanine aminotransferase was 1635 U/L. Extensive workups including viral etiologies was negative. Abdominal ultrasound revealed normal liver and no cirrhosis. The case was managed conservatively for 5 days in the hospital by giving intravenous fluid and stopping all medications. Urine toxicology screening confirmed the presence of mitragynine and diphenhydramine. He was in a stable condition with normalized liver function tests at 3 months after discharge.
Conclusion:
The COVID-19 pandemic has posed unprecedented challenges to health consequences and this case highlights the importance of kratom as potential cause of acute liver injury. Future studies should accumulate further case series and identify kratom-user subgroups or the polydrug patterns of kratom use that are at heightened risk of severe liver injury.
... Mitragyna speciosa (also known as Kratom in Thailand) is a tropical evergreen indigenous to Southeast Asia and is commonly grown in Thailand, Malaysia, Vietnam, and Papua New Guinea islands [1,2]. Mitragyna is a small genus belonging to the family Rubiaceae. ...
Mitragyna speciosa (Kratom) is a tropical narcotic plant native to Southeast Asia with unique pharmacological properties. Here, we report the first chromosome-scale assembly of the M. speciosa genome. We employed PacBio sequencing to obtain a preliminary assembly, which was subsequently scaffolded using the chromatin contact mapping technique (Hi-C) into 22 pseudomolecules. The final assembly was 692 Mb with a scaffold N50 of 26 Mb. We annotated a total of 39,708 protein-coding genes, and our gene predictions recovered 98.4% of the highly conserved orthologs based on the BUSCO analysis. The phylogenetic analysis revealed that M. speciosa diverged from the last common ancestors of Coffea arabica and Coffea canephora approximately 47.6 million years ago. Our analysis of the sequence divergence at fourfold-degenerate sites from orthologous gene pairs provided evidence supporting a genome-wide duplication in M. speciosa, agreeing with the report that members of the genus Mitragyna are tetraploid. The STRUCTURE and principal component analyses demonstrated that the 85 M. speciosa accessions included in this study were an admixture of two subpopulations. The availability of our high-quality chromosome-level genome assembly and the transcriptomic resources will be useful for future studies on the alkaloid biosynthesis pathway, as well as comparative phylogenetic studies in Mitragyna and related species.
... Traditionally, indigenous people have used it for centuries without regarding it as "drug use," but rather as a way of life, embedding it in traditions and customs similar to the Western coffee consumption (1). Ethnopharmacologically, it also gained value in selfmanaging pain, cough, diarrhea, and to enhance energy and stamina when engaging in hard manual labor (2). In time it has also gained popularity as an opioid substitute, to relieve opioid withdrawal symptoms and aid in abstinence (3). ...
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.
... Fresh kratom leaves were chewed to increase work efficiency and relieve fatigue for manual laborers in Southeast Asia (Suwanlert, 1975). Fresh and dried leaves were also brewed into teas in Malaysia and Thailand for a range of ailments including diabetes, diarrhea, fever, pain, and for use as a wound poultice (Ahmad and Aziz, 2012;McCurdy et al., 2020). ...
Kratom (Mitragyna speciosa) belongs to the coffee family of Rubiaceae. The tree is native to Southeast Asia and primarily grown in Malaysia, Thailand, and Indonesia. Recently, it has been introduced and cultivated in other countries including the United States. The leaves and extracts of the leaves are used for medicinal and recreational purposes. In February 2022, kratom root and soil samples were submitted to the University of Florida Nematode Assay Laboratory for diagnosis by a commercial grower in Florida. Root galls were observed on the roots. On examination of soil and root samples, it is revealed that high numbers of root-knot nematodes (Meloidogyne sp.) are present. Molecular species identification was performed by a combination of the mitochondria haplotyping and species-specific primer techniques using TRNAH/MHR106 and MORF/MTHIS primer sets and Meloidogyne incognita-specific primers (MIF/MIR). The root-knot nematode infecting kratom is identified as M. incognita by molecular analysis. To our knowledge, this paper is the first report of M. incognita infecting kratom in the United States.
... Following cessation of regular kratom use by humans, dependence and withdrawal syndrome have been observed. Other adverse effects associated with kratom use include liver toxicity and neurological symptoms such as dizziness and drowsiness (Suwanlert, 1975;Ahmad and Aziz, 2012;Saingam et al., 2013;Singh et al., 2018). A large number of human case reports have described signs of intoxication and even death following kratom ingestion. ...
Abstract The current report summarises the work performed in the context of the European Food Risk Assessment Fellowship Programme (EU‐FORA), which included the evaluation of health risks associated with the consumption of botanical preparations of Mitragyna speciosa (kratom). Mitragyna speciosa is a tree native to Southeast Asia, where its leaves and preparations of the leaves have been used for centuries, among others, as a stimulant or as a traditional herbal medicine. Preparations of the plant have recently gained increasing popularity in other parts of the world, and are presently also accessible via online platforms, e.g. as food supplements. Kratom has been considered a botanical of possible health concern by the FDA and EFSA, which together with its increasing popularity, makes kratom a subject of international concern. Major alkaloids of the plant, mitragynine and 7‐hydroxymitragynine, are agonists of the μ‐opioid human receptor and are assumed to be mainly responsible for its psychoactive effects. The aim of the present project was to conduct an assessment of potential health risks associated with oral use of kratom‐based preparations. The animal and human data that were evaluated in the course of the current assessment indicate that kratom consumption has the potential to not only lead to adverse neurological effects, including addiction and withdrawal syndrome, but also to elicit distinct organ toxicity with respect to e. g. liver and kidney as target organs. Nevertheless, actual risk characterisation is impeded by considerable uncertainties. Such uncertainties, based on the variability in composition of kratom preparations, insufficient information on dose–response relationships and on limited data on long‐term use effects, currently do not allow the derivation of distinct health based guidance values for kratom/kratom preparations. Further information from well‐designed studies, conducted with kratom preparations that have been clearly defined with respect to their composition, would be required to enable a more refined risk assessment of this botanical.
Methamphetamine (METH) consumption is associated with aggression. Decoction derived from the kratom (Mitragyna speciosa Korth.) leaf has been used as a METH substitute in Southeast Asia. Given its perceived benefit, we investigated the relationship between kratom use and aggression in a treatment sample of METH users with and without kratom use history. Four hundred and three male METH users participated in this cross-sectional study. A semi-structured questionnaire and several objective clinical measures were administered. Results indicate that there were no significant differences in aggression and its dimensions between METH users with and without kratom use history. However, two distinct Clusters (1 and 2) of METH users with kratom use history were studied. Users in Cluster 1 were characterized by a higher quantity and frequency of daily kratom use, longer duration of kratom use, and use of kratom at a younger age. Users in Cluster 2 exhibited the opposite characteristics. Kratom dependence and the first age of kratom use were identified as risk factors for aggression in Cluster 1. The frequency of daily kratom use appeared as a protective factor against aggression in Cluster 2. The results offer partial support to the instrumental kratom use concept; lower frequency (1 to 3 times) of kratom use may potentially minimize aggression in METH users presenting with mild to moderate kratom dependence.
Kratom/ketum is a psychoactive herbal preparation that has been used for a long time as a remedy and performance-enhancing substance in Southeast Asia. The advancement of globalization is making kratom increasingly more available in the western world, where it is becoming increasingly more used.
The current research on kratom and its ingredients is presented.
An overview of the use and effects of kratom is exemplary given on the basis of reports. The instrumentalization of the drug and its consequences up to the development of addiction are discussed.
Consumption is accompanied by several instrumentalizeable effects so that kratom is used as a therapeutic substance in the self-management of pain, anxiety and depression as well as other substance addictions. Another benefit comes from the performance-enhancing effects on physical work and in a social context. Consumption is usually well controlled, rarely escalates and has few and mostly mild aversive side effects. The danger arises from consumption particularly when there is an escalation of the dose and from mixed consumption with other psychoactive substances. The main alkaloid mitragynine and the more potent 7‑hydroxy-mitragynine are considered mainly responsible for the effect. Both have a complex pharmacology that involves partial µ‑opioid receptor agonism.
Epidemiological, clinical and neurochemical studies have shown that kratom only has a limited addictive drug profile, which might suggest a medical use as a remedy or substitute in addiction treatment.
Kratom (Mitragyna speciosa) is a substance derived from botanical compounds native to Southeast Asia. This substance has been cultivated predominantly in Thailand, Malaysia, Vietnam, and Myanmar, where it has historically been used in traditional medicine as a near panacea for several health problems. Such ritualistic use of kratom has been present for centuries; however, recreational use appears to have increased globally, especially in the United States. Pharmacodynamic and pharmacokinetic studies have found that kratom demonstrates a unique parabolic, dose-dependent pattern of effects ranging from stimulation to opioid and analgesic effects. Pharmacological research indicates that kratom is both a mu opioid receptor (μ-OR; MOR) and a kappa opioid receptor (κ-OR; KOR) agonist, which mediates its analgesic effects. Other research suggests that kratom may simultaneously act on dopaminergic and serotonergic receptors, which mediate its stimulant effects. This chapter reviews the literature related to the structural, functional, and cultural characteristics of kratom use. We begin with an overview of current and historical patterns of kratom, followed by a review of data on the pharmacodynamics and pharmacokinetics of kratom thus far.
Mitragyna speciosa, also known as Kratom, is an evergreen tree native to Southeast Asia that has been used in traditional medicine to relieve pain. The primary active alkaloid, mitragynine, found in Kratom leaves affects the same µ-receptor as the opioids. The potential effects of Kratom leaves on humans draw international concerns. The purpose of this study is to develop an efficient extraction method for mitragynine from dried Kratom leaves. Mitragynine was extracted from grounded Kratom leaves by liquid-liquid extraction and detected by an HPLC system with a C-18 column. The extracted sample was eluted with a mobile phase of 0.05% formic acid and acetonitrile (50:50, v/v), flow rate = 1.0 mL/min. Mitragynine was detected at 223 nm. The amount of mitragynine in four different strains of Kratom leaves was determined (wt/wt). Intra-day (n = 3) and inter-day(n = 3) studies show excellent precision with RSD < 2.1% and RSD < 3.6% respectively.
Kratom (
Mitragyna speciosa
Korth) is a common tropical plant found in Southeast Asia. Its leaves possess medicinal properties and are used to treat various ailments. However, the effects of kratom extract in terms of biological domains are still concerning. Although considerable studies have been conducted on the effects of kratom usage over the last few years, no study using in silico analysis of kratom users’ electrocardiogram (ECG) has been reported to date. This study aims to examine the long-term effects of kratom consumption using the ECG signals and deep learning (DL) network and machine learning techniques. Raw ECG signals were used as input for training and detecting abnormalities, and a deep residual learning network (DRLN) model was implemented to develop a feature extractor from single-lead datasets; the extracted features were used to train conventional machine learning classifiers. The confounding ECG abnormality factors, namely, age, sex, smoking, alcohol consumption, and exercise, were analyzed for association using the chi-square test. The main results of our study showed that kratom usage is not associated with ECG abnormalities. However, the ECG signal was affected more by gender than by the other factors; it exhibited the highest sensitivity and specificity (score
=
0.63). While this study is limited to ECG abnormalities, the results indicate that long-term usage of kratom for its health benefits may be considered a safe and natural practice.
Background:
Mitragyna speciosa or Kratom has been used in Thailand traditionally for its medicinal value. Despite case reports of kratom consumption causing adverse effects, research on its long-term health impact is limited. This study examines the long-term health impact of kratom use among people in Southern Thailand.
Methods:
Three community-based surveys were conducted from 2011 to 2015. In the first and second surveys (2011 and 2012) a total of 1,118 male respondents comprising 355 regular kratom users, 171 occasional kratom users, 66 ex-users, and 592 non-users aged 25 or above, were recruited from 40 villages. All respondents were followed up in this study. However, not all respondents were successfully followed up throughout the entire set of studies.
Results:
Common health complaints were no more common among kratom users than ex- and non-users, but more regular than occasional users claimed kratom to be addictive. Those with high kratom dependence scores were more likely to experience intense withdrawal symptoms, which developed 1-12 h after the last kratom intake. Over half (57.9%) of regular users had experienced intoxication effects compared to only 29.3% of occasional users. Kratom users were less likely to have a history of chronic diseases such as diabetes, hypertension, dyslipidemia than ex- and non-users.
Conclusion:
Regular long-term chewing of fresh kratom leaves was not related to an increase in common health complaints, but may pose a drug dependence risk. Severe kratom dependents were more likely to suffer from intense withdrawal symptoms. Medical records revealed no death due to traditional kratom use, but the high prevalence of tobacco or/and hand rolled cigarette smoking among kratom users should be of concern.
Mitragyna speciosa or kratom is emerging worldwide as a "legal" herbal drug of abuse. An increasing number of papers is appearing in the scientific literature regarding its pharmacological profile and the analysis of its chemical constituents, mainly represented by alkaloids. However, its detection and identification are not straightforward as the plant material is not particularly distinctive. Hyphenated techniques are generally preferred for the identification and quantification of these compounds, especially the main purported psychoactive substances, mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG), in raw and commercial products. Considering the vast popularity of this recreational drug and the growing concern about its safety, the analysis of alkaloids in biological specimens is also of great importance for forensic and toxicological laboratories. The review addresses the analytical aspects of kratom spanning the extraction techniques used to isolate the alkaloids, the qualitative and quantitative analytical methods and the strategies for the distinction of the naturally occurring isomers.
Kratom (Mitragyna speciosa) is a tree in the coffee family, indigenous to Southeast Asia (SEA), whose leaves have historically been used as a natural remedy and for its purported stimulating and analgesic properties. Kratom has gained popularity in recent years in the United States, where internet-based sales have driven growing numbers of people to experiment with kratom products. Kratom contains over 40 unique alkaloids displaying complex pharmacological properties including opioid- and non opioid-receptor mediated effects. Data from animal research indicates therapeutic potential of kratom; for instance, as an analgesic agent or in mitigating opioid and alcohol withdrawal symptoms. Some adverse effects and risks are also attributable to kratom and its alkaloids, including possible liver damage and potential for dependence, particularly in the context of high dosage and/or chronic administration. However, in comparison to commonly used opioid medications, these risks are generally lower for kratom, consistent with human observational data from SEA and the US. Prevalence of kratom use remains difficult to conclusively assess, with estimates ranging between 1.8 to 15.6 million kratom-using adults in the US alone. The limited human data, comprised of survey and case report, suggest kratom may be effective for pain relief, to address mood and anxiety symptoms, and as a potential future aid in the treatment of substance use disorders and drug withdrawal. Overall, limited data indicate kratom and its alkaloids warrant a significant investment of rigorous basic and clinical research to better characterize its pharmacology, potential risks, and therapeutic benefits.
Mitragynine (MG) is a pharmacologically active alkaloid derived from the leaves of Mitragyna speciosa Korth (Kratom). This plant has sparked significant interest as a potential alternative treatment for managing opioid dependence and withdrawal due to its opioid-like pharmacological effects. However, whether MG exposure would trigger opioid-seeking behaviour following abstinence has not been investigated. The present study examined the effects of MG priming on morphine-seeking behaviour in rats. Male Sprague-Dawley rats were initially trained to intravenously self-administer morphine (0.5 mg/kg/infusion) under a fixed ratio-3 schedule of reinforcement. Removal of both morphine infusions and drug-associated cues led to the subsequent extinction of the drug-seeking behaviour. Tests of reinstatement were made following exposure to a randomised order of intraperitoneal injections of MG (3, 10 and 30 mg/kg), morphine (5 mg/kg) and vehicle. Significant levels of drug-seeking behaviour were observed following extended access to morphine self-administration, which was extinguished following removal of morphine and cues indicative of morphine-seeking behaviour, supporting the relapse model. The present finding demonstrated that MG priming in a dose of 10 mg/kg resulted in the reinstatement of morphine-seeking behaviour, whereas the higher MG dose (30 mg/kg) tested suppressed the seeking response. This study indicated that exposure to a low MG dose may increase the likelihood of relapsing to opioids, suggesting that the potential of MG as a treatment for opioid management merits further scientific assessment of its ability to trigger relapse to opioid abuse.
Dietary supplements (DS) constitute a widely used group of products comprising vitamin, mineral, and botanical extract formulations. DS of botanical or herbal origins (HDS) comprise nearly 30% of all DS and are presented on the market either as single plant extracts or multi-extract-containing products. Despite generally safe toxicological profiles of most products currently present on the market, rising cases of liver injury caused by HDS – mostly by multi-ingredient and adulterated products – are of particular concern. Here we discuss the most prominent historical cases of HDS-induced hepatotoxicty – from Ephedra to Hydroxycut and OxyELITE Pro-NF, as well as products with suspected hepatotoxicity that are either currently on or are entering the market. We further provide discussion on overcoming the existing challenges with HDS-linked hepatotoxicity by introduction of advanced in silico, in vitro, in vivo, and microphysiological system approaches to address the matter of safety of those products before they reach the market.
Opioid overprescribing, with resultant overdose and death, has led to a national focus on alternative treatments for pain. With the decline in legal access to opioids, kratom has gained popularity as a legal, "natural," and easily accessible nonprescription analgesic for consumers wishing to self-medicate for pain, opioid use disorder, and other mental health conditions. While implications of kratom use in patients with chronic pain and/or opioid use disorder have been published, information on perianesthetic implications is lacking. Anesthesiologists should be informed about kratom, including the potential for unexpected physiologic derangements and adverse drug interactions resulting from complex pharmacologic activity, cytochrome P450 interactions, and common adulterations of the drug that may result in unpredictable clinical effects. This article explores the relevance of kratom to perioperative anesthetic care, including suggestions for anesthesiologists extrapolated from published information in nonoperative settings that may improve patient safety in individuals using kratom.
The objective of this study was to see how dried Mitragyna speciosa Korth leaves (DKTL) affected growth, hematological parameters, carcass characteristics, muscle chemical composition, and fatty acid profile in finishing goats. In a randomized complete block design, twenty crossbred males (Thai Native x Boer) weaned goats (17.70 ± 2.50 kg of initial body weight (BW)) were provided to the experimental animals (5 goats per treatment) for 90 days. Individual dietary treatments of 0, 2.22, 4.44, and 6.66 g/d of DKTL on a dry matter basis were given to the goats. The diets were provided twice daily as total mixed rations ad libitum. In comparison to the control diet, DKTL supplementation had no effect on BW, average daily gain (ADG), feed conversion ratio (FCR), carcass composition, meat pH, or meat color (p > 0.05). After DKTL treatment, the hot carcass weight, longissimus muscle area, oleic acid (C18:1n9), monounsaturated fatty acid (MUFA), and protein content increased, but saturated fatty acids (SFA) and ether extract decreased (p < 0.05). To summarize, DKTL supplementation can improve goat meat quality.
Kratom (Mitragyna speciosa Korth.) is a tree native to Southeast Asia with dose-dependent stimulant and opioid-like effects. Dried, powdered leaf material is among the kratom products most commonly consumed in the US and Europe, but other formulations also exist including enriched extracts, resins, tinctures, and edibles. Its prevalence in the US remains debated and the use pattern includes self-treatment of mood disorders, pain, and substance use disorders. Most of the adverse effects of kratom and its alkaloid mitragynine have been reported in the literature as case reports or part of surveys necessitating confirmation by clinical trials. Toxicities associated with kratom consumption have focused on hepatic, cardiac, and CNS effects with the potential to cause fatalities primarily as part of polydrug exposures. Kratom may also present with drug-drug interactions primarily through CYP 3A4 and 2D6 inhibition, although the clinical significance remains unknown to date. The variability in composition of commercially available kratom products complicates generalization of findings and requires further investigation by employing clinical trials. Healthcare professionals should remain cautious in counseling patients on the use of kratom in a therapeutic setting.
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