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A study of kratom eaters in Thailand

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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.

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... 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 . ...
Thesis
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. ...
Article
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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
... Kratom is illegal in some countries, although it has been legalized in other countries [29][30][31]. Many publications [32][33][34][35][36][37][38] have reported the abuse and addictive effects of this plant. The Drug Enforcement Administration (DEA) of the United States has added this plant to its list of drugs of concern, and the Food and Drug Administration (FDA) has issued a press release identifying it as an opioid with the potential for abuse, although the literature on its therapeutic and adverse effects is still lacking [39]. ...
... M. speciosa can be used against fatigue and can produce stimulant effects in low to high dosages [33,132]. Consumption of this plant under long-term and high-dose conditions could lead to several atypical effects and other effects such as anxiety, irritability, and enhanced aggression [69]. ...
... In addition, seizures and addiction are mainly experienced by individuals following long-term M. speciosa consumption, and liver toxicity can occur after M. speciosa overdose [118,133]. Individuals with long-term addiction to M. speciosa have been reported to have hyperpigmentation of the cheeks, tremors, anorexia, weight loss, and psychosis [33]. ...
Article
Full-text available
Mitragyna is a genus belonging to the Rubiaceae family and is a plant endemic to Asia and Africa. Traditionally, the plants of this genus were used by local people to treat some diseases from generation to generation. Mitragyna speciosa (Korth.) Havil. is a controversial plant from this genus, known under the trading name “kratom”, and contains more than 40 different types of alkaloids. Mitragynine and 7-hydroxymitragynine have agonist morphine-like effects on opioid receptors. Globally, Mitragyna plants have high economic value. However, regulations regarding the circulation and use of these commodities vary in several countries around the world. This review article aims to comprehensively examine Mitragyna plants (mainly M. speciosa) as potential pharmacological agents by looking at various aspects of the plants. A literature search was performed and information collected using electronic databases including Scopus, ScienceDirect, PubMed, directory open access journal (DOAJ), and Google Scholar in early 2020 to mid-2021. This narrative review highlights some aspects of this genus, including historical background and botanical origins, habitat, cultivation, its use in traditional medicine, phytochemistry, pharmacology and toxicity, abuse and addiction, legal issues, and the potential of Mitragyna species as pharmaceutical products.
... Kratom is illegal in some countries, although it has been legalized in other countries [29][30][31]. Many publications [32][33][34][35][36][37][38] have reported the abuse and addictive effects of this plant. The Drug Enforcement Administration (DEA) of the United States has added this plant to its list of drugs of concern, and the Food and Drug Administration (FDA) has issued a press release identifying it as an opioid with the potential for abuse, although the literature on its therapeutic and adverse effects is still lacking [39]. ...
... M. speciosa can be used against fatigue and can produce stimulant effects in low to high dosages [33,132]. Consumption of this plant under long-term and high-dose conditions could lead to several atypical effects and other effects such as anxiety, irritability, and enhanced aggression [69]. ...
... In addition, seizures and addiction are mainly experienced by individuals following long-term M. speciosa consumption, and liver toxicity can occur after M. speciosa overdose [118,133]. Individuals with long-term addiction to M. speciosa have been reported to have hyperpigmentation of the cheeks, tremors, anorexia, weight loss, and psychosis [33]. ...
Article
Full-text available
Mitragyna is a genus belonging to the Rubiaceae family and is a plant endemic to Asia and Africa. Traditionally, the plants of this genus were used by local people to treat some diseases from generation to generation. Mitragyna speciosa (Korth.) Havil. is a controversial plant from this genus, known under the trading name "kratom", and contains more than 40 different types of alkaloids. Mitragynine and 7-hydroxymitragynine have agonist morphine-like effects on opioid receptors. Globally, Mitragyna plants have high economic value. However, regulations regarding the circulation and use of these commodities vary in several countries around the world. This review article aims to comprehensively examine Mitragyna plants (mainly M. speciosa) as potential pharmacological agents by looking at various aspects of the plants. A literature search was performed and information collected using electronic databases including Scopus, ScienceDirect, PubMed, directory open access journal (DOAJ), and Google Scholar in early 2020 to mid-2021. This narrative review highlights some aspects of this genus, including historical background and botanical origins, habitat , cultivation, its use in traditional medicine, phytochemistry, pharmacology and toxicity, abuse and addiction, legal issues, and the potential of Mitragyna species as pharmaceutical products. Citation: Ahmad, I.; Prabowo, W.C.; Arifuddin, M.; Fadraersada, J.; Indriyanti, N.; Herman, H.; Purwoko, R.Y.; Nainu, F.; Rahmadi, A.; Paramita, S.; et al.
... Currently, no specific treatment for kratom dependence is implemented. Withdrawal symptoms from kratom's habitual use include hostility, aggression, flow of tears, wet nose, inability to work, jerky movement of the limbs and aching in the muscles and bones (Suwanlert, 1975;Vicknasingam et al., 2010;Agbas et al., 2019;Ahmad and Aziz, 2012;Singh et al., 2014). Kratom leaves contain over 40 alkaloids (Meireles et al., 2019;Harun et al., 2015;Harun et al., 2020;Hassan et al., 2017;Hassan et al., 2020), whereby mitragynine is the main indole alkaloid found in kratom's leaves (Hassan et al., 2013. ...
... Proteomics is a powerful tool to access drug effects on protein expression in the brain (Graves and Haystead, 2002) at a certain time (Amiri-Dashatan et al., 2018;Bläsig et al., 1973). The proteomic analysis has been broadly explored following morphine administration (Bodzon-Kulakowska et al., 2019;Berg et al., 2002) as well as morphine dependence (Bierczynska-Krzysik et al., 2006;Surmeier, 2018;Suwanlert, 1975;Tiang et al., 2020;Ujang et al., 2016) and withdrawal (Ujcikova et al., 2016;Li et al., 2006). For example, downregulated protein expression of glycolytic enzymes such as phosphoglycerate mutase 1, pyruvate kinase, and glyceraldehyde-3-phosphate dehydrogenase suggest that glucose metabolism was impaired after chronic morphine treatment (Ujcikova et al., 2016). ...
... The symptoms of withdrawal such as jitters, anxiety, and muscle cramps are related to hyperarousal mediated by enhanced noradrenergic activity (Kosten and George, 2002). In addition to withdrawal, kratom and mitragynine are well-known for their stimulant-like effect (Grewal, 1932a, b;Suwanlert, 1975;Jansen and Prast, 1988). Therefore, these energy-generating proteins could also contribute to energy boosting as people consumed it before working or social activities (Hassan et al., 2013;Singh et al., 2019b;Morrison, 2021;Müller et al., 2020;Neal and Sparber, 1986). ...
Article
Mitragyna speciosa, also known as kratom, has been used for mitigating the severity of opioid withdrawal in humans. Its main indole alkaloid, mitragynine, has been considered as a pharmacotherapy for pain conditions and opioid replacement therapy. However, at high doses, chronic mitragynine may also have an addiction potential. The effects of chronic action of mitragynine in the brain are still unknown. The present study developed a mitragynine withdrawal model in rats and used it for a proteomic analysis of mitragynine withdrawal effects. Mitragynine (30mg/kg, i.p.) was administered daily over a period of 14 days and then withdrawn. A proteomic analysis revealed that from a total of 1524 proteins identified, 31 proteins were upregulated, and 3 proteins were downregulated in the mitragynine withdrawal model. The Rab35 protein expression increased most profoundly in the mitragynine withdrawal group as compared to vehicle group. Therefore, it is proposed that Rab35 in the brain might be considered as a potential biomarker during mitragynine withdrawal and might be valuable target protein in developing new pharmacotherapies 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). ...
Article
Full-text available
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]. ...
Article
Full-text available
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. ...
Article
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.
... Although at least 40 alkaloids have been isolated from kratom leaves, the primary psychoactive substances in kratom are mitragynine and 7hydroxymitragynine [5]. Analysis of kratom alkaloids suggests ingestion results in the stimulation of opioid, alpha-2, and serotonin receptors [8]. With increasing popularity in the United States, anesthesiologists must understand how kratom use affects perioperative management. ...
... However, it is also possible that the delirium was a manifestation of kratom withdrawal. Kratom withdrawal can begin the day following cessation and include both physical (e.g., pain, nausea, tremors) and psychological (e.g., anger, hostility, aggression) symptoms [7,8]. Kratom withdrawal has been treated with clonidine [9], opioids [10], and benzodiazepines [11]. ...
Article
Kratom is a herbal and natural dietary supplement from Southeast Asia that is gaining popularity in the United States. Its leaves contain multiple psychoactive chemicals that stimulate opioid, alpha-2, and serotonergic receptors. Kratom is used as a stimulant and in the treatment of anxiety, pain, and opioid withdrawal. In most states, kratom can be purchased legally and is sold at smoke shops, gas stations, and online. To date, only limited data is available on the impact of habitual kratom use on patients undergoing anesthesia. The following case report highlights multiple anesthetic challenges posed by a heavy kratom user.
... Kratom is indigenous to Southeast Asia and has long been used there recreationally and medicinally to treat opium addiction [8,9]. It is an indole alkaloid and its main components, mitragynine and 7hydroxymitragynine, act as agonists at opioid receptors. ...
... Chronic users of kratom can develop dependency. Abstinence results in withdrawal symptoms similar to that of opioid withdrawal: rhinorrhea, insomnia, lacrimation, myalgias, arthralgias, myoclonus, depression, anxiety, and increased pain severity [8,13,[21][22][23]. Symptoms of kratom toxicity seen in adults include: palpitations, chest pain, tachycardia, hypertension, diaphoresis, altered mental status, agitation, central nervous system depression, seizures, diarrhea, abdominal pain and hepatotoxicity [22,23]. ...
Article
Full-text available
Kratom is an herbal alkaloid dietary supplement that acts agonistically at opioid receptors. It is increasingly used by those with opioid dependency to treat symptoms of opioid withdrawal. Classification and regulation of kratom is controversial. Currently it is unregulated, widely available and heavily advertised. Advocates tout its potential to help those with opioid dependency however risks to kratom use are well documented. It has been associated with dependency, withdrawal, toxicity and more recently neonatal abstinence syndrome (NAS) or withdrawal in newborns. For these reasons, pediatricians need to be aware of its existence and potential to impact their patients.
... In fact, claims and reports over the internet regarding its potential as a cheap opioid substitute have attracted the Western users to use kratom to self-medicate for opioid withdrawal and chronic pain, apart from being sold as a dietary supplement in recent decades in the United States and Europe (Boyer et al., 2008;Grundmann, 2017;Coe et al., 2019;Müller et al., 2020). The majority of long-term kratom users (over three-quarters) report developing dependence and an inability to cease its use, mainly due to its unpleasant withdrawal symptoms (Suwanlert, 1975;Boyer et al., 2008;Vicknasingam et al., 2010;Ahmad and Aziz, 2012;Saingam et al., 2013;Grundmann, 2017;Singh et al., 2019). Kratom and mitragynine are marketed for Western users either as a pure preparation (Cornara et al., 2013;Forrester, 2013;Coe et al., 2019) or as one herbal ingredient of "legal" or "herbal high" preparations, which are distributed in the form of powders, pills, and capsules under various names such as Krypton, K2, or Spice (Dresen et al., 2010;Arndt et al., 2011;Singh et al., 2014;Tavakoli et al., 2017). ...
... Thus far, the exact neural mechanisms that underlie these adverse effects on cognition remain elusive. In this context, little is known about low-dose mitragynine (1-4 mg/kg) despite the reported dosedependent pharmacological effects of kratom/ mitragynine-psychostimulants at low doses and opioid-like depressant effects at high doses (>5 mg/kg) (Suwanlert, 1975;Hassan et al., 2013;Saingam et al., 2013;Singh et al., 2019). Therefore, this study explores the low-and high-dose mitragynine range to reflect the spectrum of potential adverse effects on cognition and links the role of the endocannabinoid system for the first time to the best of the author's knowledge. ...
Article
Full-text available
Kratom is a widely abused plant-based drug preparation with a global interest in recent years, well beyond its native grounds in Southeast Asia. Mitragynine, its major psychoactive constituent is known to exhibit opioid-like behavioral effects with resultant neuroplasticity in the brain reward system. Its chronic administration is associated with cognitive impairments in animal studies. However, the underlying molecular mechanism for such a deficit remains elusive. In this study, the involvement of cannabinoid type-1 (CB 1 ) receptors in cognitive deficits after chronic mitragynine exposures was investigated for 28 days (with incremental dose sensitization from 1 to 25 mg/kg) in adult male Swiss albino mice using the IntelliCage ® system. Chronic high-dose mitragynine exposure (5–25 mg/kg, intraperitoneal [i.p.]), but not low-dose exposure (1–4 mg/kg, i.p.), induced hyperlocomotion, potentiated the preference for sucrose reward, increased resistance to punishment, and impaired place learning and its reversal. Comparable deficits were also observed after chronic treatments with Δ-9-tetrahydrocannabinol (THC, 2 mg/kg, i.p.) or morphine (5 mg/kg, subcutaneous). Mitragynine-, morphine-, and THC-induced learning and memory deficits were reversed by co-treatment with the CB 1 receptor antagonist, NIDA-41020 (10 mg/kg, i.p.). A significant upregulation of CB 1 receptor expression was found in the hippocampal CA1 region and ventral tegmental area after chronic high-dose mitragynine and morphine, whereas a downregulation was observed after chronic THC. In conclusion, the present study suggests a plausible role of the CB 1 receptor in mediating the dose-dependent cognitive deficits after chronic high-dose mitragynine exposure. This also highlights the potential of CB 1 receptor antagonism in ameliorating the cognitive deficits associated with long-term kratom/mitragynine consumption in humans.
... Whilst kratom has benefits, it also has been reported that they can cause dependence and addiction-like symptoms after longterm consumption in humans (Vicknasingam et al., 2010;Ahmad and Aziz, 2012;Singh et al., 2014;Singh et al., 2018a;Müller et al., 2020;Anand and Hosanagar, 2021). Kratom withdrawal symptoms include, jerky movement, muscle ache, aggression, wet nose, and hostility in natural settings (Suwanlert, 1975). Furthermore, kratom users have been reported to have difficulties in combating kratom withdrawal while trying to stop its consumption (Ahmad and Aziz, 2012;Singh et al., 2014). ...
... When a person is compelled to take a drug on a regular or continuous basis in order to achieve psychic effects on mental state, such as euphoria, and to avoid physical discomfort (withdrawal), this is referred to as drug dependence (Gupta and Gupta, 2018;Müller, 2020). Dependence in kratom is well documented in human (Suwanlert, 1975;Vicknasingam et al., 2010;Ahmad and Aziz, 2012;Singh et al., 2014). Nevertheless, although kratom has been reported to cause dependence and withdrawal signs, these symptoms are usually milder than after opiate withdrawal (Prozialeck, 2016;Saingam et al., 2016;Grundmann, 2017;Singh et al., 2018b;Swogger and Walsh, 2018). ...
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Background: Kratom or Mitragyna speciosa Korth has been widely used to relieve the severity of opioid withdrawal in natural settings. However, several studies have reported that kratom may by itself cause dependence following chronic consumption. Yet, there is currently no formal treatment for kratom dependence. Mitragynine, is the major psychoactive alkaloid in kratom. Chronic mitragynine treatment can cause addiction-like symptoms in rodent models including withdrawal behaviour. In this study we assessed whether the prescription drugs, methadone, buprenorphine and clonidine, could mitigate mitragynine withdrawal effects. In order to assess treatment safety, we also evaluated hematological, biochemical and histopathological treatment effects. Methods: We induced mitragynine withdrawal behaviour in a chronic treatment paradigm in rats. Methadone (1.0 mg/kg), buprenorphine (0.8 mg/kg) and clonidine (0.1 mg/kg) were i.p. administered over four days during mitragynine withdrawal. These treatments were stopped and withdrawal sign assessment continued. Thereafter, toxicological profiles of the treatments were evaluated in the blood and in organs. Results: Chronic mitragynine treatment caused significant withdrawal behaviour lasting at least 5 days. Methadone, buprenorphine, as well as clonidine treatments significantly attenuated these withdrawal signs. No major effects on blood or organ toxicity were observed. Conclusion: These data suggest that the already available prescription medications methadone, buprenorphine, and clonidine are capable to alleviate mitragynine withdrawal signs rats. This may suggest them as treatment options also for problematic mitragynine/kratom use in humans.
... Removal of the leaf veins and addition of salt is claimed to overcome constipation and other side effects. The leaves are also used in cooking; for example, as a spice in stews and for wrapping fish [21]. There are two types of kratom leaves: leaves with the red veins and leaves with the white-green veins (Fig. 5.1D). ...
... There are two types of kratom leaves: leaves with the red veins and leaves with the white-green veins (Fig. 5.1D). There are opposing reports on the potency of these two types of kratom leaves: Chittrakarn et al. claimed that stronger biological activities are produced by the red vein variety compared to the white-green vein leaves [22], while Suwanlert reported the contrary [21]. Although kratom usage is banned in Malaysia, it is easily accessible at low prices in the northern states of Malaysia, namely Kedah and Perlis [23,24]. ...
Chapter
Mitragyna speciosa (kratom), a Southeast Asian plant belonging to the Mitragyna genus, has a long history of traditional uses. There are several therapeutic properties attributed to kratom such as energy booster, pain reliever, mood enhancer, remedy for various ailments, and management of opiate addiction. In recent years, kratom leaves and derivatized botanical products (e.g., extracts, solutions) are being sold as dietary supplements and marketed worldwide via the internet for the management of pain, anxiety, and depression. Indole and oxindole alkaloids are the major chemical constituents that are most likely implicated in the pharmacological effects of kratom products. In Western countries, other than in Southeast Asia, several issues have been alarming, such as adulteration, substitution, and spiking the plant material with neuropharmacological and illicit substances. This chapter provides a summary of the ethnobotany and alkaloid chemistry of kratom including plant biosynthesis and chemical synthesis of alkaloid molecules. Recent developments in the alkaloid detection methods for kratom profiling and authentication of kratom products are also discussed in this chapter. Additionally, this chapter discusses a compilation of the available information from the literature related to the CNS exposure and interaction of major kratom alkaloids.
... 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. ...
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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. ...
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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). ...
Article
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). ...
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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. ...
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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.
... 16 Previous research suggests that chronic Mitragyna speciosa users develop an addiction and experience withdrawal symptoms following abstinence. 17 Although the responses are quite varied, Kratom abuse has received increased attention from a number of governments including Thailand and Malaysia 16 as well as the United States, United Kingdom and Germany. 18 Research has led to the discovery of more than 40 alkaloids associated with Kratom 19,20 with mitragynine and, to a lesser extent 7-hydroxymitragynine, speciogynine and, paynantheine, considered the major alkaloids. ...
Article
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Although an emerging drug of concern in the United States and Europe, the active alkaloids associated the Mitragyna speciosa plant have long been utilized for a number of purposes ranging from use as an antitussive to that of anti-inflammatory or analgesic purposes. Known by a number of common names, in the United States it is normally legally sold as Kratom. However, little is known about the consequences of the main constituent, mitragynine or any of the more than two dozen identified plant alkaloids on neuropsychological development, learning and memory, and behavior. In the present experiment, adolescent rats were given repeated injections of saline, 15 mg/kg, or 50 mg/kg of Mitragyna speciosa extract. Once the animals reached 107 days of age, they were assessed for general activity, retention on a step-down passive avoidance task, trained using tasks with spatial components of various levels of difficulty, a spatial learning set task, and a plus maze response learning task. In some but not all of the Morris water maze tasks, escape latencies for the 50 mg/kg but not 15 mg/kg rats were significantly longer than that of saline control animals. Nonetheless, performance across groups on probe trials was comparable. In addition, during learning set testing the escape times for the three groups were comparable and, more important, they were able to respond on trial two on the basis of what they learned on the first trial by the end of training. For plus maze response learning testing, all three groups made a comparable number of reference memory errors. Conversely, the 50 mg/kg drug group made significantly more total and working memory errors than the saline-treated animals. The results suggest that chronic exposure to the alkaloids present in legally available Kratom during adolescence is capable of producing a variety of subtle but lasting changes affecting spatial and working memory performance in adulthood, well after the exposure to Kratom has ended.
... 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). ...
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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%.
... Thus, the different doses of Kratom consumption were investigated with the proposed EEG-biomarkers. The doses of Kratom consumption in this study were divided into low to moderate doses (1-3 leaves/day), moderate to high doses (4-9 leaves/day), and very high dose (≥ 10 leaves/day) according to the previous study [42] and in relative to the weight of Kratom leaves in Thai origin [43]. We found that both TAR and PVF in the alpha bands tended to be the dose-dependent effect as given in Figure 6 5. ...
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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, ${K}$ -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.
... Kratom/ Ketum is a psychoactive plant preparation derived from Mitragyna speciosa Korth. Its use is well established in Southeast Asia for its narcotic and stimulant-like effects (Jansen and Prast, 1988;Suwanlert, 1975;Hassan et al., 2013;Singh et al., 2019). The traditional use and potential abuse of M. speciosa preparations as well as its purified active compound, mitragynine, have been well-reported in Southeast Asia, Europe and the US (Boyer et al., 2008;Boyer et al., 2007;Kapp et al., 2011;McWhirter and Morris, 2010;Müller et al., 2020Müller et al., , 2021. ...
Article
Kratom, derived from the plant Mitragyna speciosa (M. speciosa) Korth is a traditional psychoactive preparation widely used in Southeast Asia and increasingly in the rest of the world. Use and abuse of Kratom preparations can be attributed to mitragynine (MIT), the main psychoactive compound isolated from its leaves. While MIT may have beneficial effects as a recreational drug, for pain management, and for opiate withdrawal, it may have an addiction potential at higher doses. However, its action in the reward system of the brain is currently unknown. This study investigated how mitragynine (10 mg/kg, i.p.) affects extracellular activity of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and caudate putamen (CPu) of the brain, compared to morphine (MOR; 10 mg/kg, i.p.) and methamphetamine (METH; 10 mg/kg, i.p.). Using in-vivo microdialysis in freely moving rats, we found a significant increase of extracellular DA after MOR and METH, but not after MIT in all three brain regions. MIT led to a significant increase of DOPAC and/or HVA in these brain regions while MOR and METH had only moderate effects. These findings suggest a strong and prolonged effect of MIT on DA synthesis/metabolism, but not on extracellular DA activity, which may limit the addiction risk of MIT, in contrast to MOR and METH.
... Similarly, regular kratom use in humans leads to dependence problems in over 50% of users (Singh et al., 2014), and kratom withdrawal symptoms equally have been widely reported in humans (Singh et al., 2014;Saref et al., 2019;Stanciu et al., 2019;Anand and Hosanagar, 2021). Likely attributed to its potency at the µOR, another side effect of 7hydroxymitragynine in mice is hyperlocomotion (Becker et al., 2000;Gutridge et al., 2020); this effect mirrors one of kratom's traditional uses as a stimulant (Suwanlert, 1975;Ahmad and Aziz, 2012). Still, relative to traditional opioids such as morphine, the negative side effect profile of kratom and kratom opioids is slightly lessened in regards to reward, respiratory depression, and withdrawal symptoms (Hemby et al., 2019;Wilson et al., 2020Wilson et al., , 2021. ...
Article
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Background and Purpose: Mitragyna speciosa extract and kratom alkaloids decrease alcohol consumption in mice at least in part through actions at the δ-opioid receptor (δOR). However, the most potent opioidergic kratom alkaloid, 7-hydroxymitragynine, exhibits rewarding properties and hyperlocomotion presumably due to preferred affinity for the mu opioid receptor (µOR). We hypothesized that opioidergic kratom alkaloids like paynantheine and speciogynine with reduced µOR potency could provide a starting point for developing opioids with an improved therapeutic window to treat alcohol use disorder. Experimental Approach: We characterized paynantheine, speciociliatine, and four novel kratom-derived analogs for their ability to bind and activate δOR, µOR, and κOR. Select opioids were assessed in behavioral assays in male C57BL/6N WT and δOR knockout mice. Key Results: Paynantheine (10 mg∙kg−1, i.p.) produced aversion in a limited conditioned place preference (CPP) paradigm but did not produce CPP with additional conditioning sessions. Paynantheine did not produce robust antinociception but did block morphine-induced antinociception and hyperlocomotion. Yet, at 10 and 30 mg∙kg−1 doses (i.p.), paynantheine did not counteract morphine CPP. 7-hydroxypaynantheine and 7-hydroxyspeciogynine displayed potency at δOR but limited µOR potency relative to 7-hydroxymitragynine in vitro, and dose-dependently decreased voluntary alcohol consumption in WT but not δOR in KO mice. 7-hydroxyspeciogynine has a maximally tolerated dose of at least 10 mg∙kg−1 (s.c.) at which it did not produce significant CPP neither alter general locomotion nor induce noticeable seizures. Conclusion and Implications: Derivatizing kratom alkaloids with the goal of enhancing δOR potency and reducing off-target effects could provide a pathway to develop novel lead compounds to treat alcohol use disorder with an improved therapeutic window.
... In this study, we presented data confirming that mitragynine at low and high doses increase the efflux of DA after repeated exposure. We presumed that, at low dose, mitragynine elevates the DA level and correlate this with the kratom users whereby chewing the leaves make them feel happy, strong and active for five to ten minutes post-consumption [24]. In this work, Fig. 3b depicts that, mitragynine at low dose produced a rapid elevation during the first 30 min followed by abrupt decline. ...
Article
Background Mitragynine, the major indole alkaloid from Mitragyna speciosa has been reported previously to possess abuse liability. However, there are insufficient data suggesting the mechanism through which this pharmacological agent causes addiction. Aims In this study, we investigated the effects of mitragynine on dopamine (DA) level and dopamine transporter (DAT) expression from the rat’s frontal cortex. Methods DA level was recorded in the brain samples of animals treated with acute or repeated exposure for 4 consecutive days with either vehicle or mitragynine (1 and 30 mg/kg) using electrochemical sensor. Animals were then decapitated and the brain regions were removed, snap-frozen in liquid nitrogen and immediately stored at −80°C. DA level was quantified using Enzyme linked immunosorbent assay (ELISA) kits and DAT gene expression was determined using quantitative real time polymerase chain reaction (RT-qPCR). Results /outcome: Mitragynine (1 and 30 mg/kg) did not increase DA release following acute treatment, however, after repeated exposure at day 4, mitragynine significantly and dose dependently increased DA release in the frontal cortex. In this study, we also observed a significant increase in DAT mRNA expression at day 4 in group treated with mitragynine (30mg/kg). Conclusion /interpretation: Data from this study indicates that mitragynine significantly increased DA release when administered repeatedly, increased in DAT mRNA expression with the highest tested dose (30mg/kg). Therefore, the rewarding effects observed after mitragynine administration could be due to its ability to increase DA content in certain areas of the brain especially the frontal cortex.
... Overall, considering the flexible task design and longitudinal monitoring in a social cage environment, the IntelliCage system indicates invaluable and promising abilities to be a novel model for short-term and long-term SUD studies for other substances of abuse. Therefore, based on this knowledge, our laboratory had successfully designed a new protocol (Iman et al., 2017), which was an adaptation from Radwanska and Kaczmarek's mice alcohol addiction model (Radwanska and Kaczmarek, 2012), for the study of extended behavioral and cognitive effects of socially interacting Swiss albino mice chronically exposed to the widely abused substances, i.e., morphine, -9-tetrahydrocannabinol (THC), and mitragynine, a major alkaloid of Thai medicinal plant, kratom or Mitragyna speciosa Korth leaves, with psychostimulant and opioid-like properties (Suwanlert, 1975;Ahmad and Aziz, 2012;Hassan et al., 2013;Saingam et al., 2013;Iman et al., 2017). In brief, data collected from our IntelliCage sensitization model (Iman et al., 2017) effectively presented the behavioral and cognitive impairment evoked by the chronic administration of morphine, THC, and mitragynine, which are consistent with the reports from previous studies using conventional animal addiction assays (Justinova et al., 2009;Lu et al., 2010;O'Brien et al., 2013;Harvey-Lewis et al., 2015;Yusoff et al., 2016;Vanderschuren et al., 2017;Hassan et al., 2019). ...
Article
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The use of animal models for substance use disorder (SUD) has made an important contribution in the investigation of the behavioral and molecular mechanisms underlying substance abuse and addiction. Here, we review a novel and comprehensive behavioral platform to characterize addiction-like traits in rodents using a fully automated learning system, the IntelliCage. This system simultaneously captures the basic behavioral navigation, reward preference, and aversion, as well as the multi-dimensional complex behaviors and cognitive functions of group-housed rodents. It can reliably capture and track locomotor and cognitive pattern alterations associated with the development of substance addiction. Thus, the IntelliCage learning system offers a potentially efficient, flexible, and sensitive tool for the high-throughput screening of the rodent SUD model.
... Nonetheless, with weak law enforcement, Kratom is still consumed extensively, especially among workers in the agricultural sector. Farmers use Kratom as a stimulant drug for prolonged work under the scorching sun to relieve pain and ease muscle ache ( Suwanlert, 1975 ). The active ingredients are Mitragynine and 7-hydroxymitragynin. ...
Article
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Kratom (Mitragyna speciosa Korth.) is an indigenous plant of Southeast Asia, which has been used in traditional medicine for centuries. Despite local communities in Southern Thailand viewing Kratom as a traditional remedy and not as an illicit drug, Thailand criminalized Kratom in 1943 which has led to tensions between government authorities and local communities. This study employed a mixed-method design to explore alternative ways to decriminalize Kratom, using a Participatory Action Research framework to develop a community charter to better manage Kratom in Tambon Namphu, a rural sub-district in Southern Thailand. Quantitative data consisted of face-to-face surveys with 457 Tambon Namphu residents, 104 students and teachers and on-line self-complete surveys conducted with 1,058 people outside Tambon Namphu. Qualitative data were collected using focus groups, in-depth interviews and through public forums conducted with Tambon Namphu residents. Survey results indicate that most participants agreed with decriminalization of both Kratom cultivation and consumption and typically reported positive attitudes towards people who use Kratom. The most common reasons for supporting Kratom decriminalization were Kratom's perceived benefits for work productivity and health. People had more positive attitudes towards the consumption of fresh Kratom leaves than Kratom decoctions which were deemed more harmful. Participatory action research methods were used to pilot the development of a community consensus framework for Kratom control in Donsai, a village of 127 households. Following successful piloting, the community consensus framework on Kratom control was adopted in Donsai, adapted across Tambon Namphu and then extended to cover 135 villages across Thailand.
... Concern over its use was not raised until recently, when it became largely available in Western countries and its toxic potential realized. A first Malaysian report found kratom consumers to develop addiction and psychiatric symptoms (12), while its psychoactive properties were detailed in the late 1980s (13). ...
Article
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Kratom or Mitragyna speciosa (Korth.) is an evergreen tree of the coffee family native to South-East Asia and Australasia. It is used by locals recreationally to induce stimulant and sedative effects and medically to soothe pain and opiate withdrawal. Its leaves are smoked, chewed, or infused, or ground to yield powders or extracts for use as liquids. It contains more than 40 alkaloids; among these, mitragynine and 7-hydroxymitragynine are endowed with variable mu, delta, and kappa opioid stimulating properties (with 7-hydroxymitragynine having a more balanced affinity), rhynchophylline, which is a non-competitive NMDA glutamate receptor antagonist, but is present in negligible quantities, and raubasine, which inhibits α1-adrenceptors preferentially over α2-adrenceptors, while the latter are bound by 7-hydroxymitragynine, while mitragynine counters 5-HT2A receptors. This complexity of neurochemical mechanisms may account for kratom's sedative-analgesic and stimulant effects. It is commonly held that kratom at low doses is stimulant and at higher doses sedative, but no cut-off has been possible to define. Long-term use of kratom may produce physical and psychological effects that are very similar to its withdrawal syndrome, that is, anxiety, irritability, mood, eating, and sleep disorders, other than physical symptoms resembling opiate withdrawal. Kratom's regulatory status varies across countries; in Italy, both mitragynine and the entire tree and its parts are included among regulated substances. We describe the case of a patient who developed anxiety and dysphoric mood and insomnia while using kratom, with these symptoms persisting after withdrawal. He did not respond to a variety of antidepressant combinations and tramadol for various months, and responded after 1 month of clomipramine. Well-being persisted after discontinuing tramadol.
... M. speciosa is native to Southeast Asia and traditionally was used to combat fatigue, treat pain, as a relaxant, and as a stimulant (Suwanlert 1975). However, M. speciosa has emerged in recent years as an herbal remedy to treat not only pain, but also to alleviate symptoms associated with opiate withdrawal as well as use as a psychostimulant (Boyer et al. 2008;McWhirter and Morris 2010;Nelsen et al. 2010). ...
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Mitragyna speciosa (kratom) produces numerous compounds with pharmaceutical properties including the production of bioactive monoterpene indole and oxindole alkaloids. Using a linked-read approach, a 1,122,519,462 bp draft assembly of M. speciosa ‘Rifat’ was generated with an N50 scaffold size of 1,020,971 bp and an N50 contig size of 70,448 bp that encodes 55,746 genes. Chromosome counting revealed that ‘Rifat’ is a tetraploid with a base chromosome number of 11, which was further corroborated by orthology and syntenic analysis of the genome. Analysis of genes and clusters involved in specialized metabolism revealed genes putatively involved in alkaloid biosynthesis. Access to the genome of M. speciosa will facilitate an improved understanding of alkaloid biosynthesis and accelerate production of bioactive alkaloids in heterologous hosts.
... Withdrawal and cravings also have been reported. [5][6][7][8] There is now substantial evidence showing it is possible for individual kratom users to meet all Diagnostic and Statistical Manual, Fifth Edition (DSM-5) criteria associated with a substance use disorder diagnosis. 9 A category for "kratom use disorder" (KUD)-as we coin in this paper-does not formally exist in the DSM-5, which was last revised in 2013. ...
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Objectives: An increasing number of Americans are turning to kratom for self-management of various pain, anxiety, and mood states and as an opioid substitute. Addiction to this unique botanical develops and carries a high relapse risk and, to date, there are no guidelines on how to maintain long-term abstinence. The aim of this article is to compile all available information on management of "kratom use disorder" (KUD)-as coined here-from the literature, with evidence from the clinical practice of expert addictionologists in an attempt to develop a standard of care consensus. Methods: A systematic literature search was conducted to capture all relevant cases pertaining to maintenance treatment for KUD. Results were supplemented with case reports and scientific posters gleaned from reliable online sources and conference proceedings. Additionally, a survey of members of the American Society of Addiction Medicine (ASAM) was administered to assess the practice patterns of experts who treat patients with KUD in isolation of a comorbid opioid use disorder (OUD). Results: Based on a literature review, 14 reports exist of long-term management of KUD, half of which do not involve a comorbid OUD. Pharmacological modalities utilized include mostly buprenorphine but also a few cases of naltrexone and methadone, all with favorable outcomes. This is supported by the results of the expert survey, which demonstrated that those who have managed KUD in isolation of a comorbid OUD reported having utilized buprenorphine (89.5%), as well as the other medications for opioid use disorder (MOUD). Conclusions: This is the first comprehensive review to examine the existing literature referring to management of KUD in combination with a survey of current experts' clinical consensus regarding pharmacological management. Based on this information, it seems reasonable that the indication for MOUD should be extended to cases of moderate to severe KUD.
... Withdrawal and cravings also have been reported. [5][6][7][8] There is now substantial evidence showing it is possible for individual kratom users to meet all Diagnostic and Statistical Manual, Fifth Edition (DSM-5) criteria associated with a substance use disorder diagnosis. 9 A category for "kratom use disorder" (KUD)-as we coin in this paper-does not formally exist in the DSM-5, which was last revised in 2013. ...
Article
Full-text available
ABSTRACT Objectives: An increasing number of Americans are turning to kratom for self-management of various pain, anxiety, and mood states and as an opioid substitute. Addiction to this unique botanical develops and carries a high relapse risk and, to date, there are no guidelines on how to maintain long-term abstinence. The aim of this article is to compile all available information on management of “kratom use disorder” (KUD)—as coined here—from the literature, with evidence from the clinical practice of expert addictionologists in an attempt to develop a standard of care consensus. Methods: A systematic literature search was conducted to capture all relevant cases pertaining to maintenance treatment for KUD. Results were supplemented with case reports and scientific posters gleaned from reliable online sources and conference proceedings. Additionally, a survey of members of the American Society of Addiction Medicine (ASAM) was administered to assess the practice patterns of experts who treat patients with KUD in isolation of a comorbid opioid use disorder (OUD). Results: Based on a literature review, 14 reports exist of long-term management of KUD, half of which do not involve a comorbid OUD. Pharmacological modalities utilized include mostly buprenorphine but also a few cases of naltrexone and methadone, all with favorable outcomes.This is supported by the results of the expert survey, which demonstrated that those who have managed KUD in isolation of a comorbid OUD reported having utilized buprenorphine (89.5%), as well as the other medications for opioid use disorder (MOUD). Conclusions: This is the first comprehensive review to examine the existing literature referring to management of KUD in combination with a survey of current experts’ clinical consensus regarding pharmacological management. Based on this information, it seems reasonable that the indication for MOUD should be extended to cases of moderate to severe KUD.
... also known as kratom or ketum (biak-biak), is a medicinal plant native to Southeast Asia. 1 However, findings from numerous studies have shown that long-term kratom use can gradually lead to dependence. [2][3][4] As a result of its addictive potential and other adverse effects, kratom use is regulated in Malaysia under the Poisons Act 1952, 5 ...
Article
Background: Kratom (Mitragyna speciosa Korth.) is a traditional folk remedy used in Southeast Asia and is known to have a significant opioid-like effect. However, it is unknown whether kratom consumption can impair quality of life (QoL). This study aimed to examine the QoL of people who use kratom by comparing it with that of healthy non-kratom using controls and to determine the association between patterns of kratom use and QoL among people who use kratom. Methods: 200 respondents (100 subjects who use kratom and 100 healthy controls) were recruited for this cross-sectional study. The World Health Organization Quality of Life-BREF was administered to all the respondents to assess QoL, while the Kratom Dependence Scale (KDS) was used to assess the severity of kratom dependence among the subjects who use kratom. Results: The physical health, psychological, and environment QoL scores of the subjects who use kratom were significantly lower than those of the healthy controls. Multiple linear regression analysis revealed greater KDS score and longer duration of kratom use were significant predictors of physical health QoL, while only greater KDS score significantly predicted psychological and environment QoL scores. Conclusion: Prolonged kratom use and kratom dependence may negatively impact the QoL of people who use kratom, hence kratom addiction has to be treated adequately.
... Traditionally, kratom leaves have been used by local men, particularly in the northern states of Malaysia for medicinal and recreational purposes (Kamarudin and Zoriah 2012). Studies by Chittrakarn, Penjamras & Keawpradub (2012) and Suwanlert (1975) reported that people in Thailand have used kratom cocktail drinks which are popular for energy boosting and mood altering for many decades. Samihah, Siti Alida and Rusniah (2018) found that kratom use in Malaysia is associated with drug addicts and teenagers who consume kratom drink in their drug-use activities either for opiatereplacement or as social drinks. ...
Article
Kratom story in Malaysia is a bit intricate. Kratom (Mitragyna speciosa Korth) or local name ketum is a local plant where ‘mitragynine’ (alkaloid in kratom leaves) is listed as psychotropic substances under the Malaysian Poison Act 1952. The law stated that any activities related to possessing, selling, using, transporting, processing, importing, exporting of kratom are considered illegal and can be prosecuted. Interestingly, kratom trees are not illegal plant and no laws in Malaysia forbid the cultivation or presence of naturally growing kratom. On the prosecution side, the current laws do little to prosecute kratom addicts for rehabilitation due to no available kratom test kits which can assist the enforcement agency to arrest and prosecute kratom addicts. Therefore, the enforcement of law on kratom has been largely applied for transporting, processing and selling. Though the Poison Act cannot stop anyone who wants to plant or grow kratom there are land laws that prohibit the plantation of kratom on land specified for agriculture purpose, adding tricky situation to the present circumstances of kratom. In pharmacology, there is research and development demand for kratom, and demands from international pharmaceutical companies for kratom had created illegal rational economic exploitation of Malaysia’s kratom by individuals, so to speak resulting in more intricacies to existing complication. This paper intends to discuss the legal status of kratom in Malaysia which we believe is facing its cross-road. The paper uses the rational approach of economic and criminology arguments to establish kratom offences in the northern states of Malaysia, thus to offer a review to the current state-of-affair. A police statistics and data on kratom offences are then presented to discuss current status and its implication.
Article
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.
Article
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.
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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.
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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.
Article
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.
Article
Objective: The increasingly widespread use of kratom in the United States has raised concerns about its safety as well as spurring research into potential applications of its active ingredients in medical treatments. Methods: We reviewed the literature published over the past 20 years, including peer-reviewed publications and data released by United States government health agencies to provide an overview of this topic. Results: A variety of potentially beneficial and adverse effects of kratom use related to its opioid and stimulant properties have been documented, including addiction and withdrawal. Preliminary research in animals and case reports in humans have suggested medical utility for kratom in treating alcohol and opioid use disorders, pain, depression, and anxiety. However, the lack of controlled, standardized studies limits the clinical utility of this agent and is a barrier to safe consumption. Conclusions: Historically, kratom has been used for medical purposes and for the treatment of alcohol and substance use disorders. The currently available literature suggests a potential for similar clinical applications. However, without controlled research studies or regulation, kratom poses numerous health risks to consumers.
Article
Background: Kratom, a tree native to Southeast Asia, is increasingly used in Western countries for self-treatment of pain, psychiatric disorders, and mitigation of withdrawal symptoms from drugs of abuse. Because kratom is solely supplied from its native locations, supply shortages during the COVID-19 pandemic may impact the availability of preparations and hence force consumers to change their patterns of use. The aim of this study was to understand if and how COVID-19 was influencing kratom purchasing and use. Methods: Additional questions specific to kratom availability and changes in use during COVID-19 were added to an international online survey with responses collected between January and July 2020. During the same period, kratom-related social media posts to Twitter, Reddit, and Bluelight were analyzed for themes similar to the survey questions. Results: The survey results indicated no changes in kratom use patterns although the sample size was relatively small (n = 70) with younger consumers reporting a potential issue in obtaining their desired products from their usual sources. The survey respondents identified primarily as non-Hispanic whites (87.1%). Social media themes revolved primarily around quitting kratom during COVID-19, misinformation about the effects of kratom on COVID-19, and other non-COVID-related discussions. While some consumers may increase their kratom dose because of additional stress, a majority of discussions centered around reducing or rationing kratom due to COVID-19 or a perceived dependence. Access to quality kratom products was also a major discussion topic on social media. Conclusions: Kratom use patterns did not change due to COVID-19 but consumers were concerned about potential product shortages and resulting quality issues. Clinicians and public health officials need to be informed and educated about kratom use as a potential mitigation strategy for substance use disorders and for self-treatment of pain.
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Co-use of non-medical opioids (NMO) and methamphetamine is increasing. So too is the use of the psychoactive botanical “kratom,” including among people with NMO and methamphetamine use histories. We assessed characteristics associated with respondent groups who reported lifetime methamphetamine and/or kratom use within a nationally representative US sample using 2019 National Survey on Drug Use and Health data from respondents reporting lifetime NMO use (diverted prescription opioids, heroin). Weighted prevalence estimates for demographic, mental health, and substance use outcomes were determined. Logistic regression examined associations between group membership and outcomes. Among this sample of respondents with lifetime NMO use, 67.6% (95% CI = 65.6–69.4%) reported only NMO use; 4.6% (3.9–5.4%) reported NMO+Kratom; 24.7% (22.7–26.7%) reported NMO+Methamphetamine; and 3.2% (2.5–3.9%) reported NMO+Methamphetamine+Kratom. Compared to those in the NMO-only group, the NMO+Kratom group was more likely to report past-year serious mental illness (SMI; OR = 2.27), suicidality (OR = 1.89), and past-month psychological distress (OR = 1.88). The NMO+Methamphetamine+Kratom group was more likely to report past-year SMI (OR = 2.65), past-month psychological distress (OR = 2.06), and unmet mental health needs (OR = 2.03); increased odds for drug injection, opioid withdrawal, and perceived treatment need also emerged. Risk factors were observed for all groups but were greatest among those reporting use of all three substances.
Article
Background: Mitragyna speciosa, referred to as "kratom", is increasingly used in the United States for self-treating pain, psychiatric, and substance use disorder symptoms. It is used by some to attenuate opioid withdrawal and as a longer-term drug substitute. Most self-report data have come from online surveys, small in-person surveys, and case reports. These may not be representative of the broader kratom-using population. Purpose: Analyze user-generated social media posts to determine if independent, descriptive accounts are generally consistent with prior U.S. kratom survey findings and gain a more nuanced understanding of kratom use patterns. Methods: Reddit posts mentioning kratom from 42 subreddits between June 2019-July 2020 were coded by two independent raters. Findings: Relevant posts (number of comments, upvotes, and downvotes) from 1274 posts comprised the final sample (n = 280). Of the 1521 codes applied, 1273 (83.69%) were concordant. Desirable kratom effects were described among a majority, but so too were adverse effects. Reports of kratom as acute self-treatment for opioid withdrawal were more prominent compared to longer-term opioid substitution. Quantitative analysis found higher kratom doses associated (p < .001) with greater odds of reported kratom addiction (OR = 3.56) or withdrawal (OR = 5.88), with slightly lower odds of desirable effects (OR = 0.53, p = .014). Despite perceived therapeutic benefits, kratom was characterized by some in terms of addiction that, in some cases, appeared dose-dependent. Polydrug use was also prominently discussed. Conclusions: Results validated many prior survey findings while illustrating complexities of kratom use that are not being fully captured and require continued investigation.
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Kratom ingestion for its psychotropic effect or to self-treat opioid withdrawal symptoms has increased over the last 10 years in the United States. Although mild adverse effects have been observed in users, reports of respiratory failure and shock after kratom consumption remain rare. In this case, a 35-year-old man initially presented to the emergency department with profound circulatory shock, metabolic acidosis, hypoxia, and symptoms of autonomic nervous system dysfunction. The patient required vasopressor support, multiregimen sedation and rapid sequence intubation, mechanical ventilation, and emergent hemodialysis. Within 72 hours, the patient's condition stabilized, and he was extubated. The patient reported regular consumption of large quantities of kratom as well as injection of heroin and cocaine. In this report, a rare clinical presentation after kratom ingestion is described.
Chapter
Solanum is one of the largest genera of the family Solanaceae comprising > 2000 species distributed mostly in the tropical and subtropical regions of Australia, Africa, and some parts of Asia, such as China, India, and Japan. The nutraceutical and pharmaceutical values of the Solanum species are due to the presence of bioactive phyto-constituents such as steroidal saponins, steroidal alkaloids, terpenes, flavonoids, lignans, sterols, phenolic compounds, coumarins, etc. Among them, the presence of steroidal alkaloids and glycoalkaloids serves as major chemical markers of this genus. Steroidal alkaloids and glycoalkaloids have a special status in traditional and modern systems of medicine possessing a wide range of bioactivities, viz., antimicrobial, analgesic, hepatoprotective, immunomodulatory, anticancer, neurogenetic, etc. Steroidal alkaloids (STAs) are the major class of secondary metabolites found not only in plants but also in higher animals as well as in some aquatic invertebrates. They have a steroidal (cyclopentanophenanthrene) backbone skeleton with a nitrogen atom. The biosynthesis of these alkaloids takes place from steroids or triterpenoid pathway, on the basis of which they are further divided into different classes and subclasses. The present review is focused on the occurrence and biosynthesis of steroidal alkaloids in Solanaceae family. These compounds are mainly triterpene-derived molecules that are involved in various defense responses participating also in formulations of a wide range of phyto-pharmaceuticals. The addition of sugar moieties to the base skeleton by glycosyltransferases resulted in the formation of steroidal glycoalkaloids (STGAs), possessing a wide range of pharmacological values. The accumulation of these bioactive metabolites has been shown to be highly influenced by environmental and geographical factors. Hence, their production via tissue culture always offers an attractive alternate production platform. The current trends and biotechnological tools recently developed for the sustainable production and up-scaling of these bioactive constituents are focused in the present review.
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Genus Styrax belongs to the family Styracaceae, which is widely distributed in tropical and subtropical regions and has been applied in pharmacological uses and food chemical products. Original research articles related to Styrax plants are now abundant, but there has not been an overview account to demonstrate the highlights in phytochemical and pharmacological aspects of Styrax constituents. This chapter compiles a full list of secondary metabolites from this genus, along with their pharmacological effects. Herein, 165 isolated compounds are summarised with diverse chemical structures, and lignans and triterpenoids can be seen as major components. Pharmacological studies have introduced the use of Styrax components in anticancer, antioxidant, anti-inflammation, antimycobacterial, antiaging, antivirus HIV, and antischistosomicidal activities, estrogenic biosynthesis, etc. Regarding food chemistry, several Styrax plants can also be good candidates to provide essential oils and nutrient content of protein, especially benzoin resins.
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Mitragyna speciosa, a tropical tree also known as kratom, is an emerging substance of abuse with dose-dependent stimulant and opioid-like effects. Kratom may be purchased legally in the United States and is marketed online as a safe alternative to opioids and a cheap alternative to opioid replacement therapy. However, adverse reactions to ingestion are largely unknown and may pose a significant public health risk. This article describes a man with an intracerebral hemorrhage possibly secondary to kratom ingestion.
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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.
Article
Background Kratom (Mitragyna speciosa Korth.) is a medicinal plant, widely used in Southeast Asia chiefly for its unique medicinal properties in treating chronic pain, opioid dependence and withdrawal, and as a mood enhancer. Method Relevant articles describing kratom's medicinal utility was identified and reviewed. Results In traditional settings, laborers chew fresh leaves or ingest a kratom decoction (tea) as a stimulant that increases work performance, while those with opioid use disorder (OUD) use kratom as an affordable substitute for opioids. Though kratom is alleged to cause adverse health effects if used frequently over prolonged periods, its use has not been linked to any major health threat in traditional settings. Conclusion Currently, kratom’s pharmacological and long-term safety profile remains poorly elucidated and warrants further research. This paper provides a brief account of possibly overlooked medicinal potential of kratom.
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