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Motives for Using Kratom (Mitragyna speciosa Korth.) among Regular Users in Malaysia
Abstract
Ethnopharmacological relevance: The leaves of Mitragyna speciosa (Korth.) or kratom have been traditionally used in Malaysia and Thailand mainly to enhance work productivity, as a folk remedy for treating common ailments, and as a mood enhancer. Aim of the study: This present study sought to investigate kratom use motives among regular kratom users in Malaysia. Materials and methods: A total of 116 regular kratom users were recruited for this cross-sectional survey. The Drinking Motives Questionnaire (DMQ) was administered to measure kratom use motives. Results: Our results indicate that heavy (>3 glasses daily, each glass contains 48.24–50.4 mg of mitragynine) kratom use was associated with coping (t87.09 =3.544, p < 0.001), and enhancement (t114 =2.180, p = 003). Single subjects had higher mean scores on the coping domain, relative to married subject (t113.89 =3.029, p < 0.003), while those earning more than RM1500 per month had higher mean scores on the enhancement domain, compare to those earning less than RM1500 per month (t107 =2.151, p < 0.034). Higher scores on the coping domain was significantly associated with higher (>3 glasses daily) kratom consumption (p < 0.0045). Conclusions: Coping was associated with high (>3 glasses daily) kratom consumption among regular kratom users in traditional, rural settings.
... The leaves of the Kratom tree (Mitragyna speciosa, Rubiacaea), which is native to Southeast Asia, have a long traditional use as both a stimulant, analgesic, and for a range of other ailments. [1][2][3][4] In recent years, various leaf preparations have become popular in the US and globally due to their perceived analgesic and opioid-like effects. [5][6][7][8][9] Based on national representative surveys between 0.7-6.1% of US adults report kratom use during their lifetime or in the past year. ...
... More broadly, many posts provided further evidence that some, irrespective of COVID-19, relied on kratom to self-treat pain, serve as a drug substitute, or ameliorate psychiatric symptoms, findings which have been observed across multiple self-report studies. 2,4,5,[13][14][15][16][17]31,53 Many of these posts also reveal the extent to which the online kratom-using community relies on mutual support and information-sharing among peers, perhaps indirectly indicating the lack of availability of scientific data on kratom, the lack of consistency across kratom products, and a potential reluctance to speak openly about use to loved ones or medical providers. 28,53 Because social media allows sharing of unscientific sources, unsupported claims of medical properties of kratom can be circulated such as its supposed and unproven immune-modulating effects that can lead to potential drug interactions or self-treatment of serious disorders. ...
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.
... Several instrumentalization goals served by Kratom have been documented (Hassan et al., 2013(Hassan et al., , 2017. Those include stress coping, enhanced work performance, and better socializing (Singh et al., 2019a). Mitragynine is the main psychoactive alkaloid in Kratom, which has only weak euphoric and reinforcing effects in the dose range humans voluntarily consume (Singh et al., 2019b). ...
... The self-control of psychological or psychiatric problems is one of the major instrumentalization goals for which neurobiological mechanisms started to emerge (Ahmed et al., 2020;Müller, 2020). In that respect, the current case provides an example for regular Kratom instrumentalization also in other cultures than those, which have cultivated this drug for hundreds of years and established a well-known J o u r n a l P r e -p r o o f instrumentalization range (Singh et al., 2019a). However, it should be noted that drug instrumentalization cannot be observed directly, but has to be concluded from consumption patterns and reported benefits for other, non-addiction related behaviors. ...
Background
Kratom is a psychoactive plant preparation originating from Southeast Asia. It has been used as a recreational and performance drug in Southeast Asia, and is now increasingly used in Europe and the U.S.
Case report
We describe the case of a 63-year-old man who presented for treatment after his long-term Kratom use failed as a self-management for persistent major depression (ICD 10: F33.2) and a generalized anxiety disorder (ICD-10: F41.1). The failure coincided with emerging stress at the beginning of the COVID-19 pandemic. The patient suffered from childhood on from ruminative thinking and depressive mood, which was treated in several settings during his life. He started to use alcohol to control his depression, but developed an alcohol addiction. This was successfully treated and the patient remained abstinent for more than 25 years afterwards. About 7 years ago, he started to use Kratom 3-4 times daily on a regular, but constant rate. Kratom use worked efficiently as a self-management of his depression with no escalation of dosing. It was also very effective in reducing Morbus Menière symptoms of tinnitus and sudden hearing loss, which eventually allowed regular performance as a caregiver in a demanding job on shift-work. During recently increased stress load in the work environment and the COVID-19 pandemic, the established Kratom doses failed to control hyperarousal and mental nervousness. The patient was treatment seeking and subsequently detoxified from Kratom. Anxiety- and depression management was shifted to treatment attempts with Lorazepam, Venlafaxine, Opipramol, Mirtazapine and psychotherapy.
Conclusion
Kratom instrumentalization for self-management of depression and anxiety may effectively work without causing escalation of drug use and addiction, but may be limited by a temporary increase in psychological stress load and a relapse into major depression and generalized anxiety disorder.
... Some effects of kratom consumption, as reported by users, may be mistakenly attributed to the presence or absence of mitragynine. A cross-section survey of Malaysian kratom users indicated that medical efficacy of kratom tea consumption was maximized when consumed within 24 h of brewing (Singh et al., 2019). Effectiveness of kratom tea was reported to decrease when consumed 48 and 72 h after brewing. ...
... Effectiveness of kratom tea was reported to decrease when consumed 48 and 72 h after brewing. However, laboratory analysis of the kratom tea found no differences in mitragynine concentrations throughout the 72-h period (Singh et al., 2019). Thus, results suggest changes in compounds other than mitragynine may play a much more significant role in reported medical effectiveness of kratom than what is currently understood. ...
Leaves harvested from the Southeast Asian tree Mitragyna speciosa (kratom) have a history of use as a traditional ethnobotanical source of medicine to combat fatigue, improve work productivity, and to reduce opioid-related withdrawal symptoms. Kratom leaves contain an array of alkaloids thought to be responsible for the bioactivity reported by users. Interest in the consumptive effects of kratom has led to its recent popularity and use in North America, Western Europe, and Australia. Although the chemistry and pharmacology of select kratom alkaloids are understood, studies have not examined the influence of production environment on growth and alkaloidal content. To directly address this need, 68 kratom trees were vegetatively propagated from a single mother stock to reduce genetic variability and subjected to four varying fertilizer application rates. Leaves were analyzed for chlorophyll concentration, biomass, and alkaloidal content to understand the physiological response of the plant. While increasing rates of fertilizer promoted greater plant growth, relationships with alkaloidal content within leaves were highly variable. Fertility rate had little influence on the concentration of mitragynine, paynantheine, speciociliatine, mitraphylline, and corynoxine per leaf dry mass. 7-Hydroxymitragynine was below the lower limit of quantification in all the analyzed leaf samples. Low to medium rates of fertilizer, however, maximized concentrations of speciogynine, corynantheidine, and isocorynantheidine per leaf dry mass, suggesting a promotion of nitrogen allocation for secondary metabolism occurred for these select alkaloids. Strong correlations (r² = 0.86) between extracted leaf chlorophyll and rapid, non-destructive chlorophyll evaluation (SPAD) response allowed for development of a reliable linear model that can be used to diagnose nutrient deficiencies and allow for timely adjustment of fertilization programs to more accurately manage kratom cultivation efforts. Results from this study provide a greater understanding of the concentration and synthesis of nine bioactive alkaloids in fresh kratom leaves and provide foundational information for kratom cultivation and production.
... Further, the human equivalent dose for the highest dose of mitragynine (30 mg/kg) is 4.6 mg/kg (for a man with a body weight of ~60 kg). According to a previous study [73], humans consumed an average of 3 glasses of kratom juice per day, which equated to 145.05 mg of mitragynine per day (or 2.42 mg/kg). However, the mitragynine content for daily intake in humans could be lower or higher due to variations in alkaloid content in kratom leaves that are dependent on weather, geographical origins and age of the leaves [74,75]. ...
Kratom (M. speciosa Korth) is an herbal plant native to Southeast Asia. The leaves have been widely used to alleviate pain and opioid withdrawal symptoms. However, the increasing trend of recreational use of kratom among youth is concerning because substance abuse may render the adolescent brain more susceptible to neuropathological processes, causing dramatic consequences that persist into adulthood. Therefore, the present study aimed to investigate the long-term effects of mitragynine, the main alkaloid and lyophilized kratom decoction (LKD) exposure during adolescence on cognitive behaviours and brain metabolite profiles in adult rats. Adolescent male Sprague-Dawley rats were given mitragynine (3, 10 or 30mg/kg) or LKD orally for 15 consecutive days during postnatal days 31-45 (PND31-45). Behavioural testing was performed during adulthood (PND70-84) and the brains were subjected to metabolomic analysis. The results show that a high dose of mitragynine impaired long-term object recognition memory. Social behaviour and spatial learning were not affected, but both mitragynine and LKD impaired reference memory. Brain metabolomic study revealed several altered metabolic pathways that may be involved in the cognitive behavioural effects of LKD and mitragynine exposure. These pathways include arachidonic acid, taurine and hypotaurine, pantothenate and CoA biosynthesis, and tryptophan metabolism, while the N-isovalerylglycine was identified as the potential biomarker. In summary, adolescent kratom exposure can cause long-lasting cognitive behavioural deficits and alter brain metabolite profiles that are still evident in adulthood. This finding also indicates that the adolescent brain is vulnerable to the impact of early kratom use.
... In den Ursprungsländern des Kratoms, erfolgt der regelmäßige Konsum aber meist vor dem Hintergrund, Erschöpfungserscheinungen vorzubeugen und die Arbeitsleistung zu steigern und weniger des Rausches wegen. Deshalb würde man in diesen Fällen lediglich den Wunsch die Produktivität zu steigern und weniger Anzeichen für Abhängigkeit oder Sucht erkennen(Singh et al., 2019a). Das könnte auch der Grund für die niedrige Inzidenz von Kratom-Konsumstörungen und anderen Nebenwirkungen bei traditionellen Konsumenten in den Herkunftsländern sein(Singh et al., 2019b, Singh et al., 2018a, Singh et al., 2018b). ...
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.
... Mitragynine is an active indole alkaloid from Mitragyna speciosa (Kratom) with marked abuse liability that has been used in Malaysia and Thailand as a recreational drug and herbal high [1][2][3][4][5]. Mitragynine administration was previously reported to cause memory impairments in rodents [4,[6][7][8]. ...
Mitragynine, an indole alkaloid from the plant Mitragyna speciosa (Kratom), has been reported to modify hippocampal synaptic transmission. However, the role of glutamatergic neurotransmission modulating synaptic plasticity in mitragynine-induced synaptic changes is still unknown. Here, we determined the role of AMPA- and NMDA glutamate receptors in mitragynine-induced synaptic plasticity in the hippocampus. Male Sprague Dawley rats received either vehicle or mitragynine (10 mg/kg), with or without the AMPA receptor antagonist, NBQX (3 mg/kg), or the NMDA receptor antagonist, MK-801 (0.2 mg/kg). Field excitatory postsynaptic potentials (fEPSP) during baseline, paired-pulse facilitation (PPF) and long-term potentiation (LTP) were recorded in-vivo in the hippocampal CA1 area of anaesthetised rats. Basal synaptic transmission and LTP were significantly impaired after mitragynine, NBQX, and MK-801 alone, without an effect on PPF. Combined effects suggest a weak functional AMPA- as well as NMDA receptor antagonist action of mitragynine.
... Common motive for kratom consumption are either coping (t87.09 =3.544, p < 0.001) and enhancement (t114 =2.180, p = 0.03), with higher coping score correlate with higher daily dose of kratom consumption (Singh et al., 2019b). Some reasons included in these criteria are chronic pain, self-medication, opiate addiction, anxiety, and stress. ...
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
... 3 The leaves are the only part of the tree that is used for their effects and are either chewed fresh for a brief period of time by farmers, laborers, or fishermen to obtain a stimulant effect and reduce or prevent fatigue from hard labor or the fresh or dried leaves are used to prepare a water decoction for later consumption. 6 Less commonly, the dried leaf may also be smoked to achieve a relaxing effect. 7 The historical use of kratom as both a stimulant and for pain relief has remained common practice even in Southeast Asian countries where the official sale and use of kratom are banned or not endorsed by the government, such as Malaysia or Indonesia. ...
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.
... Its leaves are ovate-acuminate in shape, with glossy dark green color and could grow to over 14-20 cm in length, and 7-12 cm wide (Raffa, 2014;Raffa et al., 2013;Ratsch, 2005). Kratom has been used traditionally for various treatments, including fatigue, cough, pain, colds, diarrhea, diabetes, hypertension, increased stamina and sexual prowess, and opium withdrawal (Suwanlert, 1975;Chua and Schmelzer, 2001;Ratsch, 2005;Assanangkornchai et al., 2007;Tanguay, 2011;Singh et al., 2019). Due to its opioid activity, kratom gaining *Corresponding author : Endang Lukitaningsih Email : lukitaningsih_end@ugm.ac.id popularity as a recreational psychoactive drug (Prozialeck et al., 2012;Cinosi et al., 2015). ...
The extraction of kratom (M. speciosa) leaf powder was optimized with preliminary extraction to be further optimized with the Box-Behnken experimental design. The individual and interactive effects of process variables (sample-to-solvent ratio, extraction time, solvent concentration) were assessed. The preliminary extraction results showed that ultrasound-assisted extraction (UAE) and methanol were chosen for further optimization. The experimental data were analyzed by Pareto analysis of variance (ANOVA) and second-order polynomial models were developed using multiple regression analysis. The model developed showed a good fit with the experimental data with a high coefficient of correlation (R2) and predictive ability (predicted R2). An optimization study was performed and the optimal extraction conditions were sample-to-solvent ratio value 1.5:10; extraction time of 10 minutes, and methanol concentration of 100%.
... November 2021 | Volume 12 | Article 751656 least 14 subtypes from seven distinct families, 5-HT1-5-HT7 (Nichols and Nichols, 2008). Kratom has long been used as a mood enhancer, mild stimulant, or aphrodisiac in traditional settings in Malaysia and Thailand (Singh et al., 2019;Singh et al., 2020b). However, research into its potential interaction with the human serotonin neurotransmission system is still in its early stages. ...
Parallel to the growing use of kratom, there is a wealth of evidence from self-report, preclinical, and early clinical studies on therapeutic benefits of its alkaloids in particular for treating pain, managing substance use disorder, and coping with emotional or mental health conditions. On the other hand, there are also reports on potential health risks concerning kratom use. These two aspects are often discussed in reviews on kratom. Here, we aim to highlight specific areas that are of importance to give insights into the mechanistic of kratom alkaloids pharmacological actions. This includes their interactions with drug-metabolizing enzymes and predictions of clinical drug-drug interactions, receptor-binding properties, interactions with cellular barriers in regards to barrier permeability, involvement of membrane transporters, and alteration of barrier function when exposed to the alkaloids.
... 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. ...
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.
... Kratom has been widely used as an energy booster and pain reliever to fight off fatigue and to improve work productivity (Assanangkornchai et al. 2007;Vicknasingam et al. 2010). In Malaysia and Southern Thailand, Kratom is widely used by the locals as a substitute for opium in addicts (Tanguay 2011;Vicknasingam et al. 2010;Singh et al. 2019a). ...
Rationale
The treatment of opiate addiction is an unmet medical need. Repeated exposure to opiates disrupts cognitive performance. Opioid substitution therapy, with, e.g., methadone, may further exacerbate the cognitive deficits. Growing evidence suggests that mitragynine, the primary alkaloid from the Kratom (Mitragyna speciosa) leaves, may serve as a promising alternative therapy for opiate addiction. However, the knowledge of its health consequences is still limited.
Objectives
We aimed to examine the cognitive effects of mitragynine substitution in morphine-withdrawn rats. Furthermore, we asked whether neuronal addiction markers like the brain-derived neurotrophic factor (BDNF) and Ca²⁺/calmodulin-dependent kinase II alpha (αCaMKII) might mediate the observed effects.
Methods
Male Sprague–Dawley rats were given morphine at escalating doses before treatment was discontinued to induce a spontaneous morphine withdrawal. Then, vehicle or mitragynine (5 mg/kg, 15 mg/kg, or 30 mg/kg) substitution was given for 3 days. A vehicle-treated group was used as a control. Withdrawal signs were scored after 24 h, 48 h, and 72 h, while novel object recognition (NOR) and attentional set-shifting (ASST) were tested during the substitution period.
Results
Discontinuation of morphine significantly induced morphine withdrawal signs and cognitive deficit in the ASST. The substitution with mitragynine was able to alleviate the withdrawal signs. Mitragynine did not affect the recognition memory in the NOR but significantly improved the reversal learning deficit in the morphine-withdrawn rats.
Conclusions
These data support the idea that mitragynine could be used as safe medication therapy to treat opiate addiction with beneficial effects on cognitive deficits.
... 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). Yusoff et al. (2016) has reported the paw and body tremor during mitragynine withdrawal. ...
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.
... Mitragyna speciosa Korth, also known as kratom is a native medicinal plant that grows in Southeast Asia. It is commonly used as a safe herbal drug for pain relief, opioid dependence and withdrawal treatment as well as to alleviate psychological problems [8][9][10][11]. The leaves of this plant have been traditionally used as local analgesia and for opium treatment during the early 19th century in Malaya [12,13]. Rural folks commonly consumed kratom by chewing the fresh leaves, drying the leaves and ingesting it, or brewing it with tea/coffee and drinking it as a herbal solution [13]. ...
Kratom is a medicinal plant that exhibits promising results as an opiate substitute. However, there is little information regarding the abuse profile of its main psychoactive constituent, mitragynine (MG), particularly in relapse to drug abuse. Using the place conditioning procedure as a model of relapse, this study aims to evaluate the ability of MG to induce conditioned place preference (CPP) reinstatement in rats. To evaluate the cross-reinstatement effects, MG and morphine were injected to rats that previously extinguished a morphine-or MG-induced CPP. Following a CPP acquisition induced by either MG (10 and 30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A low dose priming injection of MG or morphine produced a reinstatement of the previously extinguished CPP. In the second experiment of this study, a priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated an MG-induced CPP. Likewise, a priming injection of MG (3, 10 and 30 mg/kg, i.p.) was able to dose-dependently reinstate a morphine-induced CPP. The present study demonstrates a cross-reinstatement effect between MG and morphine, thereby suggesting a similar interaction in their rewarding motivational properties. The findings from this study also suggesting that a priming exposure to kratom and an opioid may cause relapse for a previously abused drug.
... Kratom is a Southeast Asian plant of which the leaf products are widely used in this region with numerous instrumentalization goals reported (Hassan et al., 2013; including enhanced work performance and better socializing, but also to manage self-withdrawal from opiate use (Singh et al., 2019a). It has only weak euphoric effects in the dose range humans voluntarily use (Singh et al., 2019b) and is not associated with neurological or psychiatric deficits and addiction development in the vast majority of regular users in Malaysia (Singh et al., 2015(Singh et al., , 2018a2018b;Leong Bin Abdullah et al., 2019). ...
Background
Kratom is a Southeast Asian plant, which is widely used in this region, and making an increasing appearance in Europe and the US.
Case report
We present the case of a 26-year-old man in Substitol-assisted treatment of excessive Kratom and Tilidin use expressing the wish for a drug-free management of a chronic pain condition. After an accidental calcaneus impression fracture, the patient was suffering from severe chronic pain and anxiety of further accidents. This was managed initially with Tilidin. Resulting from the wish to self-manage the pain condition in a way that permitted continuation of a job, the patient searched for a ‘natural’ treatment alternative obtained from an Internet vendor. He successfully instrumentalized Kratom for 3 years with daily consumption intermixed with occasional Tilidin for pain management. However, the dose of Kratom was increased considerably up to a level of effect reversal, when no analgesic and behaviorally activating effects occurred any more, but only intense drowsiness. The patient was treatment seeking and subsequently detoxified from Kratom and Tilidin. Pain management was shifted to retarded morphine.
Conclusion
Kratom instrumentalization for pain management might appear to be more problematic for addiction development than when its use is established for other consumption motives.
Methamphetamine (METH) consumption is associated with aggression. Decoction derived from the kratom (Mitragyna speciosa Korth.) leaf has been used as a METH substitute in Southeast Asia. Given its perceived benefit, we investigated the relationship between kratom use and aggression in a treatment sample of METH users with and without kratom use history. Four hundred and three male METH users participated in this cross-sectional study. A semi-structured questionnaire and several objective clinical measures were administered. Results indicate that there were no significant differences in aggression and its dimensions between METH users with and without kratom use history. However, two distinct Clusters (1 and 2) of METH users with kratom use history were studied. Users in Cluster 1 were characterized by a higher quantity and frequency of daily kratom use, longer duration of kratom use, and use of kratom at a younger age. Users in Cluster 2 exhibited the opposite characteristics. Kratom dependence and the first age of kratom use were identified as risk factors for aggression in Cluster 1. The frequency of daily kratom use appeared as a protective factor against aggression in Cluster 2. The results offer partial support to the instrumental kratom use concept; lower frequency (1 to 3 times) of kratom use may potentially minimize aggression in METH users presenting with mild to moderate kratom dependence.
Kratom/ketum is a psychoactive herbal preparation that has been used for a long time as a remedy and performance-enhancing substance in Southeast Asia. The advancement of globalization is making kratom increasingly more available in the western world, where it is becoming increasingly more used.
The current research on kratom and its ingredients is presented.
An overview of the use and effects of kratom is exemplary given on the basis of reports. The instrumentalization of the drug and its consequences up to the development of addiction are discussed.
Consumption is accompanied by several instrumentalizeable effects so that kratom is used as a therapeutic substance in the self-management of pain, anxiety and depression as well as other substance addictions. Another benefit comes from the performance-enhancing effects on physical work and in a social context. Consumption is usually well controlled, rarely escalates and has few and mostly mild aversive side effects. The danger arises from consumption particularly when there is an escalation of the dose and from mixed consumption with other psychoactive substances. The main alkaloid mitragynine and the more potent 7‑hydroxy-mitragynine are considered mainly responsible for the effect. Both have a complex pharmacology that involves partial µ‑opioid receptor agonism.
Epidemiological, clinical and neurochemical studies have shown that kratom only has a limited addictive drug profile, which might suggest a medical use as a remedy or substitute in addiction treatment.
Background
“Kratom” refers to an array of bioactive products derived from Mitragyna speciosa, a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and common reasons for use are to address mental and physical health needs, manage pain, and to reduce use of other substances. Natural-history studies and survey studies suggest that many kratom consumers perceive benefits from those uses, but such studies are unlikely to capture the full range of kratom-use experiences.
Methods
We collected text data from Reddit posts from 2020-2022 to qualitatively examine conceptualizations, motivations, effects, and consequences associated with kratom use among people posting to social media. Reddit posts mentioning kratom were studied using template thematic analysis, which included collecting descriptions of kratom product types and use practices. Network analyses of coded themes was performed to examine independent relationships among themes, and between themes and product types.
Results
Codes were applied to 329 of the 370 posts that comprised the final sample; 134 posts contained kratom product descriptions. As Reddit accounts were functionally anonymous, demographic estimates were untenable. Themes included kratom physical dependence (tolerance, withdrawal, or use to avoid withdrawal), perceived addiction (net detrimental effects on functioning), and quitting. Extract products were positively associated with reports of perceived addiction, dependence, and experiences of quitting kratom. Many used kratom for energy and self-treatment of pain, fatigue, and problems associated with opioid and alcohol; they perceived these uses as effective. Consumers expressed frustrations about product inconsistencies and lack of product information.
Conclusion
As in previous studies, kratom was deemed helpful for some and a hindrance to others, but we also found evidence of notable negative experiences with kratom products that have not been well documented in surveys. Daily kratom use may produce mild-moderate physical dependence, with greater severity being possibly more common with concentrated extracts; however, there are currently no human laboratory studies of concentrated kratom extracts. Such studies, and detailed kratom product information, are needed to help inform consumer decision-making.
Introduction:
Kratom (Mitragyna speciosa) is a medicinal tree native to Southeast Asia. The present multilevel meta-analysis describes the association between kratom use and the positive and negative indicators of mental health.
Methods:
A total of thirty-six articles were included in the meta-analysis to examine the associations, using a random-effects model.
Results:
The pooled effect size showed a very small positive association between kratom use and negative indicators of mental health {r = 0.092, 95% confidence interval (CI) = [0.020, 0.164], p < 0.05}, while no significant association was found with positive indicators of mental health (r = -0.031, 95% CI = [-0.149, 0.087], p > 0.05). Pooled effect sizes of specific mental health outcomes indicated that kratom use showed only a small positive correlation with externalizing disorders (r = 0.201, 95% CI = [0.107, 0.300], p < 0.001). No significant association was found between kratom use and quality of life (r = 0.069, 95% CI = [-0.104, 0.242], p > 0.05) and internalizing disorders (r = -0.001, 95% CI = [-0.115, 0.095], p > 0.05). Multilevel moderator analysis showed that the pooled effect size of the association between kratom use and substance use disorder was stronger in Malaysia (r = 0.347, 95% CI = [0.209, 0.516], p < 0.001), and with the mean age (β1 = -0.035, 95% CI = [-0.055, -0.014], p = 0.003), and the drug profile of those who were not co-using other drugs (r = 0.347, 95% CI = [0.209, 0.516], p < 0.001).
Conclusion:
The meta-analysis supports the kratom instrumentalization concept, in that a positive gain from kratom consumption can be achieved without any significant adverse associations with mental health.
Although kratom use has been part of life for centuries in Southeast Asia, the availability and use of kratom in the United States (US) increased substantially since the early 2000s when there was little information on kratom pharmacology, use patterns, and effects, all critical to guiding regulation and policy. Here we provide a synthesis of research with several hundred English-language papers published in the past 5 years drawing from basic research, epidemiological and surveillance data, and recent clinical research. This review of available literature aims to provide an integrated update regarding our current understanding of kratom’s benefits, risks, pharmacology, and epidemiology, which may inform United States-based kratom regulation. Recent surveillance indicates there are likely several million past-year kratom consumers, though estimates vary widely. Even without precise prevalence data, kratom use is no longer a niche, with millions of United States adults using it for myriad reasons. Despite its botanical origins in the coffee tree family and its polypharmacy, kratom is popularly characterized as an opioid with presumed opioid-system-based risks for addiction or overdose. Neuropharmacology, toxicology, and epidemiology studies show that kratom is more accurately characterized as a substance with diverse and complex pharmacology. Taken together the work reviewed here provides a foundation for future scientific studies, as well as a guide for ongoing efforts to regulate kratom. This work also informs much-needed federal oversight, including by the United States Food and Drug Administration. We conclude with recommendations for kratom regulation and research priorities needed to address current policy and knowledge gaps around this increasingly used botanical product.
Kratom is a natural psychoactive product known primarily in Southeast Asia, including Thailand, Malaysia etc. It is also known as krathom, kakuam, ithang, thom (Thailand), biak-biak, ketum (Malaysia) and mambog (Philippines), and is sometimes used as an opium substitute. It is stimulant at doses of 1-5g, analgesic at doses of 5-15g, and euphoric and sedative at doses above 15g. Mitragynine is the most abundant indole compound in kratom (Mitragyna speciosa) and is metabolized in humans to 7-hydroxymitragynine, the more active metabolite. Adverse effects include seizures, nausea, vomiting, diarrhoea, tachycardia, restlessness, tremors, hallucinations and death. There are few studies on the analytical method for the detection of mitragynine and 7-hydroxymitragynine in hair. Therefore, this study proposes a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method for the analysis of kratom in hair. Hair samples were first weighed to approximately 10 mg and washed with methanol. Then the washed hair samples were cut into pieces and incubated in methanol with stirring and heating (16h/38℃). Extracts were then analysed by LC-MS-MS. This method was validated by determining the limit of detection (LOD), limit of quantification (LOQ), linearity, intra- and inter-day accuracy and precision, recovery and matrix effects. The intra- and inter-day precision (CV%) and accuracy (bias%) were within ±20%, which was considered acceptable. Using this newly developed LC-MS-MS method, the simultaneous detection of mitragynine and 7-hydroxymitragynine in six authentic hair samples was achieved to provide the direct evidence of kratom use in the past. Mitragynine concentrations ranged from 16.0 to 2,067 pg/mg (mean 905.3 pg/mg), and 7-hydroxymitragynine concentrations ranged from 0.34 to 15 pg/mg (mean 7.4 pg/mg) in six authentic hair samples from kratom abusers. This may be due to the higher sensitivity of the LOD in this study, with values of 0.05 pg/mg for mitragynine and 0.2 pg/mg for 7-hydroxymitragynine in hair, respectively.
Aims: This review aimed to comprehensively examine kratom’s therapeutic potential for treatment of mental health-related issues as well as any related benefits and risks. Design: Systematic review. Data sources: Google Scholar, Web of Science, PubMed, Scopus, PsycINFO, EMBASE, Cochrane Library, and Medline. Review methods: Three authors carried out electronic search of articles published between 1950 to September 2022 through major databases for a duration of three months (from July to September 2022). Each author independently screened the literature for inclusion and exclusion criteria, the findings were then compared, discrepancies between authors were resolved, and the final selection of articles were reviewed. Results: A total of 46 articles were included in this review. A total of three in vitro and animal studies and five cross-sectional online surveys reported the therapeutic potential of kratom in opioid replacement therapy. In addition, a total of two animal studies and three cross-sectional online surveys highlighted the role of kratom as a potential antidepressant and anxiolytic. Contrastingly, two animal studies, 11 studies in human subjects, and 16 case reports documented the risk of kratom dependence, cravings, tolerance, and kratom-related substance use disorder as the major safety concern of implementing kratom use as a therapeutic agent. Conclusion and impact: In the absence of human clinical trial, coupled with various considerable adverse events of kratom (not limited to psychological side effects), evidence to support kratom as potential therapeutic use remains inconclusive.
Mitragyna speciosa Korth also known as kratom, is an herbal drug preparation for its therapeutic properties and opioid-replacement therapy. Kratom is consumed in a brewed decoction form in Malaysia and to date, no studies have characterized its chemical and toxicity profile. Thus, this study aims to evaluate kratom decoction's safety and toxicity profile after 28 days of treatment. Mitragynine content was quantified in kratom decoction and used as a marker to determine the concentration. Male and female Sprague Dawley rats were orally treated with vehicle or kratom decoction (10, 50 or 150 mg/kg) and two satellite groups were treated with vehicle and kratom decoction (150 mg/kg). Blood and organs were collected for hematology, biochemical and histopathology analysis at the end of treatment. No mortality was found after 28 days of treatment and no significant changes in body weight and hematology profile, except for low platelet count. High amounts of uric acid, AST, ALT and alkaline phosphatase were found in the biochemical analysis. Histological investigation of the heart and lungs detected no alterations except for the kidney, liver and brain tissues. In conclusion, repeated administration of kratom decoction provided some evidence of toxicity in the kidney and liver with no occurrence of mortality.
Penenelitian ini bertujuan menganalisis narasi yang dibangun BNN terkait dengan kebijakan kratom serta hambatan narasi kebijakan pelarangan kratom di Indonesia. Untuk menganalisis kebijakan tersebut, peneliti menggunakan metode analisis kebijakan publik (NPA). Yaitu, metode analisis dengan menggunakan kajian narasi terdiri dari level analisis, latar belakang serta plot dan pesan moral yang ingin disampaikan dalam narasi kebijakan. Model analisis ini juga digunakan peneliti untuk menganalisis isi narasi kebijakan khususnya mengenai nilai dan strategi untuk menyampaikan kebijakan pelarangan kratom. Hasil dalam penelitian ini menemukan adanya perbedaan antara kebijakan mengenai kratom yang dilakukan oleh BNN dan kebijakan yang dibuat oleh Kementerian/Lembaga serta Pemerintah Daerah penghasil tanaman kratom. Perbedaan kebijakan inilah yang akhirnya menghambat proses regulasi kratom masuk dalam UU No. 35 Tahun 2009 tentang narkotika.
Background:
Mitragyna speciosa or Kratom has been used in Thailand traditionally for its medicinal value. Despite case reports of kratom consumption causing adverse effects, research on its long-term health impact is limited. This study examines the long-term health impact of kratom use among people in Southern Thailand.
Methods:
Three community-based surveys were conducted from 2011 to 2015. In the first and second surveys (2011 and 2012) a total of 1,118 male respondents comprising 355 regular kratom users, 171 occasional kratom users, 66 ex-users, and 592 non-users aged 25 or above, were recruited from 40 villages. All respondents were followed up in this study. However, not all respondents were successfully followed up throughout the entire set of studies.
Results:
Common health complaints were no more common among kratom users than ex- and non-users, but more regular than occasional users claimed kratom to be addictive. Those with high kratom dependence scores were more likely to experience intense withdrawal symptoms, which developed 1-12 h after the last kratom intake. Over half (57.9%) of regular users had experienced intoxication effects compared to only 29.3% of occasional users. Kratom users were less likely to have a history of chronic diseases such as diabetes, hypertension, dyslipidemia than ex- and non-users.
Conclusion:
Regular long-term chewing of fresh kratom leaves was not related to an increase in common health complaints, but may pose a drug dependence risk. Severe kratom dependents were more likely to suffer from intense withdrawal symptoms. Medical records revealed no death due to traditional kratom use, but the high prevalence of tobacco or/and hand rolled cigarette smoking among kratom users should be of concern.
Purpose of review:
This work aims to provide an up-to-date review of the preclinical and clinical scientific literature on the therapeutic value of kratom to better understand the underlying mechanisms related to its use and inform future therapeutic applications.
Recent findings:
A growing number of studies, mainly of cross-sectional nature, describe the widespread use of kratom by individuals to self-treat pain, psychiatric symptoms, and substance use disorders (SUD) outside a controlled clinical setting. Preclinical evidence suggests kratom is effective as an analgesic agent and might decrease the self-administration of other drugs. A randomized controlled trial has further supported kratom's therapeutic value as an analgesic. Investigations in nonclinical samples of long-term kratom users also indicate its therapeutic benefit in managing SUD symptoms (e.g., craving) and long-term or acute symptoms (e.g., withdrawal) for alcohol, opioids, and other illicit drugs. However, episodes of kratom-related intoxications have also been reported, often due to the adulteration and the contamination of kratom products mainly sold online or mixed toxicities when consumed outside clinical and traditional settings.
Summary:
Evidence on the clinical implications of kratom use is still limited and uncertain, with kratom research constantly evolving. Therefore, further randomized trials are needed.
Kratom (Mitragyna speciosa) is a tree in the coffee family, indigenous to Southeast Asia (SEA), whose leaves have historically been used as a natural remedy and for its purported stimulating and analgesic properties. Kratom has gained popularity in recent years in the United States, where internet-based sales have driven growing numbers of people to experiment with kratom products. Kratom contains over 40 unique alkaloids displaying complex pharmacological properties including opioid- and non opioid-receptor mediated effects. Data from animal research indicates therapeutic potential of kratom; for instance, as an analgesic agent or in mitigating opioid and alcohol withdrawal symptoms. Some adverse effects and risks are also attributable to kratom and its alkaloids, including possible liver damage and potential for dependence, particularly in the context of high dosage and/or chronic administration. However, in comparison to commonly used opioid medications, these risks are generally lower for kratom, consistent with human observational data from SEA and the US. Prevalence of kratom use remains difficult to conclusively assess, with estimates ranging between 1.8 to 15.6 million kratom-using adults in the US alone. The limited human data, comprised of survey and case report, suggest kratom may be effective for pain relief, to address mood and anxiety symptoms, and as a potential future aid in the treatment of substance use disorders and drug withdrawal. Overall, limited data indicate kratom and its alkaloids warrant a significant investment of rigorous basic and clinical research to better characterize its pharmacology, potential risks, and therapeutic benefits.
Purpose of Review
This systematic review examines case reports of kratom physical dependence or addiction, focusing on assessment, diagnosis, and treatment methods and the completeness of the clinical data presented.
Recent Findings
Most peer-reviewed clinical literature on kratom physical dependence and addiction comes in the form of case reports. However, these reports often provide incomplete descriptions of complex circumstances, and there remain no standardized assessment, diagnostic, or treatment methods for patients presenting with these morbidities.
Summary
Many reports were difficult to interpret due to missing information. Despite the lack of standardized assessment and diagnostic tools for kratom addiction, withdrawal, or dependence, medications for opioid use disorder were frequently prescribed, which is problematic for opioid naïve patients. Findings suggest that case reports involving kratom should include established standardized assessments of history and symptomatology, incorporating laboratory testing where possible. Development of best practices for treatment of kratom-associated dependence or addiction is warranted.
Background
The legal status of kratom in the United States is complex and varies by state. The U.S. Food and Drug Administration (FDA) and the U.S. Drug Enforcement Administration have repeatedly subjected kratom to regulatory review. However, there hasn't been a systematic review of the public's perception of kratom. The present study analyzed open-ended responses from the public to an FDA solicitation for information regarding kratom with the goal of providing a comprehensive assessment of motives for kratom use.
Methods
To guide decisions regarding kratom regulation, the FDA solicited comments regarding kratom abuse potential, medical usefulness, and impact of scheduling changes from July through August 2021 and posted them to the Federal Register website. We analyzed comments posted during the first 6 weeks of comment solicitation (6,353) using an inductive approach via qualitative content analysis.
Results
Respondents reported 106 independent health-related reasons for kratom use, with most categorized as mental health, pain management, substance use disorder, or miscellaneous purposes that included increasing focus, treating insomnia, and decreasing fatigue. Neurological diseases and digestive disorders were also reported. Relatively few (< 2%) responses reported recreational use, abuse potential, or adverse effects of kratom.
Conclusions
Although kratom is not approved as a safe and effective therapy for any indication, individuals use kratom for a broad spectrum of health-related purposes. Limitations of this study include potential bias for respondents with perceived positive experiences using kratom, lack of demographics data, and lack of independent verification of claims made by respondents. Regardless, this study reflects perceptions regarding the therapeutic uses of kratom and provides insight into potential individual-level consequences of regulating kratom in the U.S. It is important to study the public's perception of kratom use, which can aid regulatory purposes and provide clinically important information on individuals’ use and valuation of kratom.
Kratom is the common term for Mitragyna speciosa and its products. Its major active compounds are mitragynine and 7-hydroxymitragynine. An estimated 2.1 million US residents used kratom in 2020, as a "legal high" and self-medication for pain, opioid withdrawal, and other conditions. Up to 20% of US kratom users report symptoms consistent with kratom use disorder. Kratom use is associated with medical toxicity and death. Causality is difficult to prove as almost all cases involve other psychoactive substances. Daily, high-dose use may result in kratom use disorder and opioid-like withdrawal on cessation of use. These are best treated with buprenorphine.
Background:
Mitragyna speciosa (kratom) is increasingly used in the United States for its pharmacological effects. Kratom's relative novelty makes for a dynamic situation, such that use motivations are not firmly established and may be changing. Investigators and clinicians require frequent updates on kratom trends.
Objectives:
To assess the current state of kratom-use initiation, sourcing, motivations, preference, conceptualizations, and perceived stigma, using survey responses from current and former users.
Methods:
Between April-May 2021 we recontacted 289 respondents who reported lifetime kratom use (on an unrelated survey) to answer kratom-specific questions.
Results:
The sample (N=129) was majority female (51.9%) and white (71.9%). Most (69.0%) reported first trying kratom after 2015. Mean age of use initiation (29.9 years) was older than for other substances, including opioids. Kratom ranked as a preferred substance by 48.5%. The strongest drug association with past-year kratom use was vaped nicotine (OR=3.31,95% CI 1.23-8.88). Use was less likely among those prescribed buprenorphine in the past year (OR=0.03, CI 0.01-0.28). Past-month cannabis use (OR=4.18,CI 1.80-9.72) had the strongest association with past-month kratom use. Over 40 use motivations were endorsed, many (but not all) supporting the "self-treatment" narrative of kratom use, including use as an opioid, alcohol, or stimulant substitute. Treatment shortfalls were associated with decisions to try kratom.
Conclusions:
Kratom use motivations are diversifying, with multiple factors driving use. As sales continue to increase, the public-health, clinical, and policy responses to kratom should be grounded in rigorous bench-to-bedside scientific research. Comprehensive study of kratom is currently lacking.
There is limited understanding regarding kratom use among US adults. Although motivations for use are increasingly understood, typical kratom doses, threshold of (low and high) doses for perceived effectiveness, and effects produced during cessation are not well documented. We aimed to extend prior survey work by recruiting adults with current and past kratom exposure. Our goal was to better understand kratom dosing, changes in routines, and perception of effects, including time to onset, duration, and variability of beneficial and adverse outcomes from use and cessation. Among respondents who reported experiencing acute kratom effects, we also sought to determine if effects were perceived as helpful or unhelpful in meeting daily obligations. Finally, we attempted to detect any signal of a relationship between the amount of kratom consumed weekly and weeks of regular use with ratings of beneficial effects from use and ratings of adverse effects from cessation. We conducted an online survey between April-May 2021 by re-recruiting participants from a separate study who reported lifetime kratom use. A total of 129 evaluable surveys were collected. Most (59.7%) had used kratom >100 times and reported currently or having previously used kratom >4 times per week (62 weeks on average). Under half (41.9%) reported that they considered themselves to be a current “regular kratom user.” A majority (79.8%) reported experiencing acute effects from their typical kratom dose and that onset of effects began in minutes but dissipated within hours. Over a quarter reported that they had increased their kratom dose since use initiation, whereas 18.6% had decreased. Greater severity of unwanted effects from ≥1 day of kratom cessation was predicted by more weeks of regular kratom use (β = 6.74, p = 0.02). Acute kratom effects were largely reported as compatible with, and sometimes helpful in, meeting daily obligations. In the absence of human laboratory studies, survey methods must be refined to more precisely assess dose-effect relationships. These can help inform the development of controlled observational and experimental studies needed to advance the public health understanding of kratom product use.
Drugs are regulated in the United States (US) by the Controlled Substances Act (CSA) if assessment of their abuse potential, including public health risks, show such control is warranted. An evaluation via the 8 factors of the CSA provides the comprehensive assessment required for permanent listing of new chemical entities and previously uncontrolled substances. Such an assessment was published for two kratom alkaloids in 2018 that the Food and Drug Administration (FDA) have identified as candidates for CSA listing: mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG) (Henningfield et al., 2018a). That assessment concluded the abuse potential of MG was within the range of many other uncontrolled substances, that there was not evidence of an imminent risk to public health, and that a Schedule I listing (the only option for substances that are not FDA approved for therapeutic use such as kratom) carried public health risks including drug overdoses by people using kratom to abstain from opioids. The purpose of this review is to provide an updated abuse potential assessment reviewing greater than 100 studies published since January 1, 2018. These include studies of abuse potential and physical dependence/withdrawal in animals; in-vitro receptor binding; assessments of potential efficacy treating pain and substance use disorders; pharmacokinetic/pharmacodynamic studies with safety-related findings; clinical studies of long-term users with various physiological endpoints; and surveys of patterns and reasons for use and associated effects including dependence and withdrawal. Findings from these studies suggest that public health is better served by assuring continued access to kratom products by consumers and researchers. Currently, Kratom alkaloids and derivatives are in development as safer and/or more effective medicines for treating pain, substances use disorders, and mood disorders. Placing kratom in the CSA via scheduling would criminalize consumers and possession, seriously impede research, and can be predicted to have serious adverse public health consequences, including potentially thousands of drug overdose deaths. Therefore, CSA listing is not recommended. Regulation to minimize risks of contaminated, adulterated, and inappropriately marketed products is recommended.
The potential of mitragynine to produce physiological dependence (withdrawal) was assessed using a rapid assessment procedure with male ICR mice exposed to heroin-admixed food followed by naloxone (subcutaneously, s.c.) precipitation of withdrawal. Initial studies indicated that 3 days of exposure to 3.0 mg/g of heroin-admixed food followed by naloxone (0.6 mg/kg) reliably precipitated withdrawal jumping and weight loss. Lower concentrations of heroin-admixed food and lower doses of naloxone produced fewer withdrawal signs. A longer exposure to heroin-admixed food did not produce significantly greater amounts of jumping or weight loss. Further, these withdrawal signs were dose-dependently reversed by s.c. administration of heroin immediately following naloxone administration. Mitragynine (s.c.) also dose-dependently suppressed naloxone-precipitated withdrawal signs. Additionally, both jumping and weight loss were suppressed over a comparable range of mitragynine doses when administered by gavage with a noticeably, but not significantly, higher potency than with s.c. administration. The ED50 values for mitragynine for the suppression of withdrawal by any route (354–911 μmol/kg) were greater than the minimally effective dose that decreased locomotor activity (251 μmol/kg) and from 40- to 104-fold greater than those for heroin. The results suggest inherent opioid dependence liability of mitragynine. The in vivo potency relations between mitragynine and heroin are consistent with a conclusion of dependence-producing effects, indicated by the suppression of withdrawal, comparable to standard opioid μ-receptor agonists, differing primarily in terms of potency. The present paper provides a method for the rapid assessment of physiological dependence liability applicable to other kratom plant constituents or any potential opioid dependence-producing agents.
This chapter describes the pharmacology, clinical effects and toxicology of naturally occurring tryptamines (including dimethyltryptamine and mitragynine), and synthetic tryptamines (unsubstituted, 4-substituted and 5-substituted). A description of the diverse pharmacokinetic properties of tryptamines is followed by a review of receptor interactions, particularly serotonin receptor agonism responsible for hallucinogenic psychoactive effects. User reports detailing desired effects of tryptamines are reviewed. The chapter describes prevalence data demonstrating increasing use of synthetic tryptamines in the developed world, and the use of naturally occurring tryptamines including mitragynine outside of traditional settings. Animal and human experimental data demonstrating tryptamine toxicity is reviewed, followed by a summary of user reports describing unwanted effects. The chapter concludes by reviewing deaths associated with tryptamine exposure including deaths associated with the increasing use of mitragynine.
Kratom is a substance similar to opioids that is often used for its euphoric effects, however it can be obtained legally in most of the United States. The substance is often not assessed on routine urine drug screen, however it is estimated that millions of people engage in kratom use each year and level of use is rising. Given the increasing prevalence of kratom use, and its potentially lethal consequences, it is imperative that primary care physicians be familiar with this substance and have a framework to approach identification and treatment of individuals with kratom use disorder. This manuscript offers a review of the epidemiology and pharmacology of kratom, along with guidance for care of individuals with kratom use disorder in the primary care setting.
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.
Opioid analgesics remain a gold standard for the treatment of moderate to severe pain. However, their clinical utility is seriously limited by a range of adverse effects. Among them, their high-addictive potential appears as very important, especially in the context of the opioid epidemic. Therefore, the development of safer opioid analgesics with low abuse potential appears as a challenging problem for opioid research. Among the last few decades, different approaches to the discovery of novel opioid drugs have been assessed. One of the most promising is the development of G protein-biased opioid agonists, which can activate only selected intracellular signaling pathways. To date, discoveries of several biased agonists acting via μ-opioid receptor were reported. According to the experimental data, such ligands may be devoid of at least some of the opioid side effects, such as respiratory depression or constipation. Nevertheless, most data regarding the addictive properties of biased μ-opioid receptor agonists are inconsistent. A global problem connected with opioid abuse also requires the search for effective pharmacotherapy for opioid addiction, which is another potential application of biased compounds. This review discusses the state-of-the-art on addictive properties of G protein-biased μ-opioid receptor agonists as well as we analyze whether these compounds can diminish any symptoms of opioid addiction. Finally, we provide a critical view on recent data connected with biased signaling and its implications to in vivo manifestations of addiction.
Graphic abstract
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.
Background
Alcohol can be instrumentalized to achieve goals that without the drug would either not be achievable or would be so only with considerably more workload. While an understanding of the neurobiological mechanisms of alcohol instrumentalization is emerging, little information is available concerning instrumentalization goals in controlled consumers and how these goals change during the development of an alcohol use disorder (AUD).
Methods
We surveyed instrumentalization goals in 103 male and 78 female inpatients with AUD (before / after onset of the disorder) and compared them with the goals of 124 male and 96 female age‐matched non‐addicted controls. We also investigated whether instrumentalization goals predict 24‐month alcohol‐related hospital readmissions in the patients using a false discovery rate (FDR) approach.
Results
Separately for both sexes, the most frequently (>25%) self‐reported alcohol instrumentalization goals in patients were “stress coping,” “craving for alcohol,” and “reduction of anxiety and / or depressive mood” and in controls “facilitation of social interaction.” Relative to controls, and in a sex‐dependent manner, patients with AUD reported the goals “facilitation of social interaction” and “search for a partner” significantly less frequently and “reduction of anxiety and / or depressive mood,” “stress coping,” “improvement of sexual activity,” “improvement of concentration,” “euphoria,” and “craving for alcohol” more frequently. During the transition to addiction, many of the instrumentalization goals changed significantly, some in a sex‐dependent manner. In female AUD patients, a goal of “euphoria” nominally predicted a lower risk of alcohol‐related readmission, although not significantly when FDR corrected.
Conclusions
We identified cross‐sectional and intra‐individual differences in instrumentalization goals that support the assumption that the onset of an AUD coincides with a shift in instrumentalization goals from prosocial instrumentalization toward the self‐management of aversive mental states.
Pain management devoid of serious opioid adverse effects is still far from reach despite vigorous research and development efforts. Alternatives to classical opioids have been sought for years, and mounting reports of individuals finding pain relief with kratom have recently intensified research on this natural product. Although the composition of kratom is complex, the pharmacological characterization of its most abundant alkaloids has drawn attention to three molecules in particular, owing to their demonstrated antinociceptive activity and limited side effects in vivo. These three molecules are mitragynine (MG), its oxidized active metabolite, 7-hydroxymitragynine (7OH), and the indole-to-spiropseudoindoxy rearrangement product of MG known as mitragynine pseudoindoxyl (MP). Although these three alkaloids have been shown to preferentially activate the G protein signaling pathway by binding and allosterically modulating the μ-opioid receptor (MOP), a molecular level understanding of this process is lacking and yet important for the design of improved therapeutics. The molecular dynamics study and experimental validation reported here provide an atomic level description of how MG, 7OH, and MP bind and allosterically modulate the MOP, which can eventually guide structure-based drug design of improved therapeutics.
Kratom (Mitragyna speciosa Korth., Rubiaceae) is native to and has traditional use in Southeast Asia. The number of kratom users outside of Southeast Asia has increased significantly in recent decades with use spreading to the Unites States (US) and Europe. Because of its reputed opioid-like psychoactive effects at higher doses, kratom has been regulated in several countries and is subject to an import ban by the US Food and Drug Administration. Nonetheless, in the US it is estimated that 10–15 million people consume kratom primarily for the self-treatment of pain, psychiatric disorders, to mitigate withdrawal from or dependence on opioids, and to self-treat opioid use disorder or other substance use disorders (SUDs). Due to the global COVID-19 pandemic, a shortage in the supply of kratom products may place unexpected burdens on kratom users, potentially influencing some who use kratom for SUD self-treatment to regress to harmful drug use, hence increasing the likelihood of adverse outcomes, including overdose. Inadequate treatment, treatment barriers, and increases in the sales of adulterated kratom products on the internet or in convenience stores could exacerbate circumstances further. Although there are currently no verified indications of kratom scarcity, researchers and clinicians should be aware of and remain vigilant to this unanticipated possibility.
Among the symptoms of COVID-19 fever, general malaise, pain and aches, myalgia, fatigue, and headache can affect the quality of life of patients, even after the end of the acute phase of the infection and can be long lasting. The current treatment of these symptoms, also because COVID-19 patients have been asked not to use non-steroidal anti-inflammatory drugs (NSAIDs), in particular ibuprofen are often unsatisfactory. Among the above mentioned symptoms malaise and fatigue seem the most difficult to treat. In this case report we describe the use of kratom (Mitragyna speciosa) by a patient with confirmed COVID-19 infection. What we observed was a fast and sustained relieve of the above mentioned symptoms.
Mitragyna speciosa (Kratom) is a psychotropic tropical tree that is indigenous to Southeast Asia, Africa and New Guinea. Kratom has gained popularity in the United States in more recent years as an opioid agonist. Although Kratom is considered an opioid agonist with abuse potential, its use is not federally regulated. We report on a 47 year-old male presenting to our clinic for treatment of an opioid use disorder. This began with the use of prescription opioids from a doctor, and when this was no longer available this patient started using Kratom. He had used Kratom for one year to treat opioid withdrawal symptoms and chronic pain, resulting in worsening depression, anxiety and pain. He experienced tolerance and withdrawal symptoms related to Kratom. He was initiated on buprenorphine-naloxone at home with improved pain management. Four months after initiation, the patient’s depression and anxiety symptoms resolved, and he was able to discontinue his antidepressant and anxiolytic medications. Kratom dependence and withdrawal appear similar to that of opioids, and may also lead to worsening depression and anxiety. Buprenorphine-naloxone may be a viable option to consider for treating opioid use disorder complicated by Kratom use, chronic pain, and depression.
Psychoactive drugs with addiction potential are widely used by people of virtually all cultures in a non-addictive way. In order to understand this behaviour, its population penetrance, and its persistence, drug instrumentalization was suggested as a driving force for this consumption. Drug instrumentalization theory holds that psychoactive drugs are consumed in a very systematic way in order to make other, non-drug-related behaviours more efficient. Here, we review the evolutionary origin of this behaviour and its psychological mechanisms and explore the neurobiological and neuropharmacological mechanisms underlying them. Instrumentalization goals are discussed, for which an environmentally selective and mental state-dependent consumption of psychoactive drugs can be learned and maintained in a non-addictive way. A small percentage of people who regularly instrumentalize psychoactive drugs make a transition to addiction, which often starts with qualitative and quantitative changes in the instrumentalization goals. As such, addiction is proposed to develop from previously established long-term drug instrumentalization. Thus, preventing and treating drug addiction in an individualized medicine approach may essentially require understanding and supporting personal instrumentalization goals.
Kratom, or Mitragyna, is a tropical plant indigenous to Southeast Asia, with unique pharmacological properties. It is commonly consumed by preparing the leaves into decoction or tea, or by grinding them into a powder. Recent evidence has revealed that kratom has physiological effects similar to opioids, including pain relief and euphoria, as well as stimulant properties, which together raise potential concern for dependence and addiction. Moreover, growing evidence suggests that the prevalence of kratom use is increasing in many parts of the world, raising important considerations for healthcare providers. This manuscript will discuss the most current epidemiology, pharmacology, toxicity, and management related to kratom, while seeking to provide a contemporary perspective on the issue and its role in the greater context of the opioid epidemic.
The psychoactive plant kratom is a native plant to Southeast Asia, and its major bioactive alkaloid is mitragynine. Mitragynine exerts its analgesic properties by acting on the opioid receptors. One of its active metabolites, 7-hydroxymytraginine, is found to be 40 times more potent than mitragynine and 10 times more potent than morphine. Interestingly, current research suggests that mitragynine behaves as an atypical opioid agonist – possessing analgesic activity with less severe side effects than typical opioids. Although Thailand and Malaysia have criminalized the use, possession, growing, or selling of kratom due to its abuse potential, kratom still remains unregulated in the United States. The U.S. Drug Enforcement Agency (DEA) listed kratom as a “drug of concern” in 2008 with the intent to temporarily place mitragynine and 7-hydroxymitragynine onto Schedule I of the Controlled Substances Act. However, responses from the general public, U.S. Congress, and Kratom Alliances had the DEA retract their intent. Kratom is currently marketed in the U.S. as a dietary or herbal supplement used to treat chronic pain, anxiety, and depression with over $207 million in annual sales in the U.S. alone. Here, we will review the traditional and medicinal uses of kratom along with the synthesis of its bioactive ingredients, their pharmacology, metabolism, and structure-activity relationships. The importance in society of this currently controversial substance will also be discussed.
This study sought to determine the relationship between kratom (Mitragyna speciosa) initiation and regular consumption of illicit drugs and HIV risk behaviors in a cohort of illicit drug users in Malaysia. 260 illicit drug users with current kratom use were recruited through convenience sampling for this cross-sectional study. All were male, with the majority being Malays (95%, n = 246/260). Results suggest that kratom initiation was associated with significant decrease in the regular use of heroin (odds ratio (OR) = 0.50, 95% confidence interval (CI): 0.40– 0.72; p = .0001), methamphetamine (OR = 0.23, CI: 0.16– 0.35; p < .0001), and amphetamine (OR = 0.17, CI: 0.09– 0.34; p < .0001). Kratom initiation was also associated with reduction in regular HIV risk behaviors such as having sex with sex workers (OR = 0.20, CI: 0.12–0.32; p < .0001), using drugs before sexual intercourse (OR = 0.20, CI: 0.13– 0.31; p < .0001), injecting behaviors (OR = 0.10, CI: 0.04– 0.25; p < .0001), sharing of injection equipment (OR = 0.13, CI: 0.04– 0.43; p < .0001), and injecting with other injection drug users (IDUs) (OR = 0.07, CI: 0.02– 0.24; p < .0001).
RationaleSubstantial use of the plant kratom for psychoactive effects has driven interest in its abuse liability. Several place conditioning studies suggest abuse liability of the active ingredient mitragynine, though studies of its self-administration have not been published. Methods
Binding of mitragynine to rat brain mu, kappa, and delta opioid receptors was compared to that for heroin and morphine. Self-administration of mitragynine, heroin, methamphetamine, or saline was assessed during single-session substitutions in rats trained to self-administer methamphetamine (0.022 mg/kg/injection, i.v.) during 1-h daily sessions. ResultsMitragynine had > 2- or ~ 16-fold greater affinity for the mu opioid receptor than, respectively, for kappa or delta opioid receptors. Its affinity for the mu receptor was ~ 200-fold less than that for morphine. In rats trained to self-administer methamphetamine, saline substitutions significantly decreased the number of responses, whereas different doses of methamphetamine (0.002–0.068 mg/kg/injection) or heroin (0.001–0.03 mg/kg/injection) maintained self-administration with maximal responding at 0.022 or 0.01 mg/kg/injection, respectively. In contrast, no dose of mitragynine maintained response rates greater than those obtained with saline. Presession mitragynine treatment (0.1 to 3.0 mg/kg) decreased response rates maintained by heroin but had little effect on responding maintained by methamphetamine across the same range of doses. Conclusions
These results suggest a limited abuse liability of mitragynine and potential for mitragynine treatment to specifically reduce opioid abuse. With the current prevalence of opioid abuse and misuse, it appears currently that mitragynine is deserving of more extensive exploration for its development or that of an analog as a medical treatment for opioid abuse.
Kratom, derived from the plant Mitragyna speciosa, is receiving increased attention as an alternative to traditional opiates and as a replacement therapy for opiate dependence. Mitragynine (MG) and 7-hydroxymitragynine (7-HMG) are major psychoactive constituents of kratom. While MG and 7-HMG share behavioral and analgesic properties with morphine, their reinforcing effects have not been examined to date. 7-HMG, but not MG, substituted for morphine self-administration in a dose-dependent manner in the rat self-administration paradigm. Following the substitution procedure, re-assessment of morphine self-administration revealed a significant increase following 7-HMG and a significant decrease following MG substitution. In a separate cohort, 7-HMG, but not MG, engendered and maintained intravenous self-administration in a dose-dependent manner. The effects of pretreatment with nalxonaxine (NLXZ), a μ1 opi-ate receptor antagonist, and naltrindole (NTI), a δ opiate receptor antagonist, on 7-HMG and morphine self-administration were also examined. Both NLXZ and NTI reduced 7-HMG self-administration, whereas only NLXZ decreased morphine intake. The present results are the first to demonstrate that 7-HMG is readily self-administered, and the reinforcing effects of 7-HMG are mediated in part by μ and δ opiate receptors. In addition, prior exposure to 7-HMGincreased subsequent morphine intake whereas prior exposure to MG decreased morphine intake. The present findingsindicate that MG does not have abuse potential and reduces morphine intake, desired characteristics of candidate pharmacotherapies for opiate addiction and withdrawal, whereas 7-HMG should be considered a kratom constituent with high abuse potential that may also increase the intake of other opiates.
RationaleConsideration by the US Drug Enforcement Administration and Food and Drug Administration of placing kratom into Schedule I of the Controlled Substances Act (CSA) requires its evaluation of abuse potential in the context of public health. Objective
The objective of the study is to provide a review of kratom abuse potential and its evaluation according to the 8 factors of the CSA. ResultsKratom leaves and extracts have been used for centuries in Southeast Asia and elsewhere to manage pain and other disorders and, by mid-twentieth century, to manage opioid withdrawal. Kratom has some opioid effects but low respiratory depression and abuse potential compared to opioids of abuse. This appears due to its non-opioid-derived and resembling molecular structure recently referred to as biased agonists. By the early 2000s, kratom was increasingly used in the US as a natural remedy to improve mood and quality of life and as substitutes for prescription and illicit opioids for managing pain and opioid withdrawal by people seeking abstinence from opioids. There has been no documented threat to public health that would appear to warrant emergency scheduling of the products and placement in Schedule I of the CSA carries risks of creating serious public health problems. Conclusions
Although kratom appears to have pharmacological properties that support some level of scheduling, if it was an approved drug, placing it into Schedule I, thus banning it, risks creating public health problems that do not presently exist. Furthermore, appropriate regulation by FDA is vital to ensure appropriate and safe use.
Ethnopharmacological relevance:
Kratom (Mitragyna speciosa Korth.) from the Rubiaceae family is an indigenous tropical medicinal tree of Southeast Asia. Kratom leaves have been used for decades in Malaysia and Thailand in traditional context for its perceived vast medicinal value, and as a mild stimulant among manual labourers. Kratom consumption has been reported to cause side-effects in kratom users.
Aim of the study:
To evaluate kratom's effects towards hematological and clinical-chemistry parameters among regular kratom users in Malaysia.
Methods:
A total of 77 subjects (n=58 regular kratom users, and n=19 healthy controls) participated in this cross-sectional study. All the surveys were conducted through face-to-face interview to elicit subject's socio-demographic characteristics and kratom use history. A full-blood test was also administered. Laboratory analysis was conducted using GC-MS to determine mitragynine content in the acquired kratom samples in order to relate mitragynine consumption with possible alterations in the blood parameters of kratom users.
Results:
Findings showed that there were no significant differences in the hematological and clinical-chemistry parameters of traditional kratom users and healthy controls, except for HDL and LDL cholesterol values; these were found to be above the normal reference range for the former. Similarly, long-term kratom consumption (>5 years), and quantity of daily kratom use (≥3 ½ glasses; mitragynine content 76.3-114.8mg) did not appear to alter the hematological and biochemical parameters of kratom users.
Conclusion:
These data suggest that even long-term and heavy kratom consumption did not significantly alter the hematological and clinical-chemistry parameters of kratom users in a traditional setting.
Kratom is a traditional drug from Southeast Asia that has been an emerging new substance in the United States. On August 30, 2016, the DEA announced the intention to emergency schedule kratom into Schedule I. To support this decision, the DEA cited an increase in drug seizures of kratom and an increase in calls to poison control concerning kratom. However, a short time later, on October 12, 2016, the DEA withdrew the intent to schedule kratom after public and congressional backlash. The withdrawal by the DEA was somewhat unprecedented. To better understand both decisions, the current article examines the evidence the DEA cited to support their decision to emergency schedule kratom and the degree and type of media coverage of kratom to determine if a media-driven drug panic occurred.
Objectives. Extending individual planning of health behaviour change to the level of the dyad, dyadic planning refers to a target person and a planning partner jointly planning the target person’s health behaviour change. To date, predictors of dyadic planning have not been systematically investigated. Integrating cognitive predictors of individual planning with four established predictor domains of social support provision, we propose a framework of predictors of dyadic planning. Including target persons’ and partners’ perspectives, we examine these predictor domains in the context of prostate cancer patients’ rehabilitative pelvic floor exercise (PFE) following radical prostatectomy. Design. Longitudinal data from 175 patients and their partners were analysed in a study with four post-surgery assessments across 6 months. Methods. PFE-related dyadic planning was assessed from both partners together with indicators from four predictor domains: context, target person, partner, and relationship factors. Individual planning and social support served as covariates. Results. Findings from two-level models nesting repeated assessments in individuals showed that context (patients’ incontinence), target person (i.e., positive affect and self- efficacy), and relationship factors (i.e., relationship satisfaction) were uniquely associated with dyadic planning, whereas partner factors (i.e., positive and negative affects) were not. Factors predicting patients’ and partners’ accounts of dyadic planning differed. Conclusions. Resembling prior findings on antecedents of support provision in this context, partner factors did not prevail as unique predictors of dyadic planning, whereas indicators from all other predictor domains did. To establish predictive direction, future work should use lagged predictions with shorter intermeasurement intervals.
The use of substances to enhance human abilities is a constant and cross-cultural feature in the evolution of humanity. Although much has changed over time, the availability on the Internet, often supported by misleading marketing strategies, has made their use even more likely and risky. This paper will explore the case of
Mitragyna speciosa
Korth. (kratom), a tropical tree used traditionally to combat fatigue and improve work productivity among farm populations in Southeast Asia, which has recently become popular as novel psychoactive substance in Western countries. Specifically, it (i) reviews the state of the art on kratom pharmacology and identification; (ii) provides a comprehensive overview of kratom use cross-culturally; (iii) explores the subjective experiences of users; (iv) identifies potential risks and side-effects related to its consumption. Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.
Despite consistent evidence that alcohol can be used to cope with negative emotions or to enhance positive emotions, research on drinking motives has focused primarily on coping and social motives. This article reports on the development of a 3-factor measure that also assesses enhancement motives. Using confirmatory factor analysis, the authors demonstrated that enhancement motives are empirically distinct from coping and social motives and that a correlated 3-factor model fits the data equally well across race and gender groups in a large representative sample. Each drinking motive was also shown to predict distinct aspects of alcohol use and abuse. Finally, interaction analyses suggested that coping and enhancement motives differ in the magnitude of their effects on drinking behavior across Blacks and Whites and that enhancement motives differ in their effects across men and women. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
A 4-factor measure of drinking motives based on a conceptual model by M. Cox and E. Klinger (see PA, Vol 75:32975; see also 1990) is presented. Using data from a representative household sample of 1,243 Black and White adolescents, confirmatory factor analyses showed that the hypothesized model provided an excellent fit to the data and that the factor pattern was invariant across gender, race, and age. Each drinking motive was related to a distinct pattern of contextual antecedents and drinking-related outcomes, and these relationships did not generally vary across demographic subgroups. Results support both the conceptual validity of Cox and Klinger's model and the utility of this measure for clinical and research purposes across a diverse range of adolescent populations. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The consumption of Mitragyna speciosa (MS) for its psychoactive effects is widely reported amongst people in the villages in Thailand and Malaysia even though its use is illegal.
This study examined the pattern of MS use, its reported effects and explored its potential to cause dependence.
We used both convenience and snowball-sampling methods to recruit participants in a border town between two northern states in Malaysia. Face-to-face interviews were conducted with the use of a structured questionnaire on 562 respondents who gave oral consent to participate in the study.
The response rate was 91%. The majority of the respondents (88%) reported daily use of MS. The main mode of using MS was by drinking the MS extract as tea (90%). The mean age of starting MS use was 28.3 (SD=8.1) years. A variety of reasons were given for using MS including for social and recreational needs, stamina and physical endurance, pain relief and improved sexual performance. Despite its reported usefulness in weaning off opiate addiction, 460 (87%) admitted they were not able to stop using MS. Only education level had a statistically significant association with the ability to stop or not stop the use of MS (χ(2)=31.0, df=1, p<0.001). Significantly higher proportions of those with a lower education level (38%) were able to stop using MS compared to respondents with a higher education level.
Our study provides important information on the pattern of MS use, its effects and its potential to cause addiction, as there has been growing interest in MS as evidenced by the number of advertisements for its sale on the Internet. Future study is required to explore its psychological and social impact on users.
The leaves of Kratom, a medicinal plant in Southeast Asia, have been used as an herbal drug for a long time. At least one of the alkaloids present in Kratom, mitragynine, is a mu-receptor agonist. Both Kratom and an additional preparation called Krypton are available via the internet. It seems to consist of powdered Kratom leaves with another mu-receptor agonist, O-desmethyltramadol, added. O-Desmethyltramadol is an active metabolite of tramadol, a commonly prescribed analgesic. We present nine cases of intoxication, occurring in a period of less than one year, where both mitragynine and O-desmethyltramadol were detected in the postmortem blood samples. Neither tramadol nor N-desmethyltramadol was present in these samples, which implies that the ingested drug was O-desmethyltramadol. The blood concentrations of mitragynine, determined by ultra-performance liquid chromatography-tandem mass spectrometry, ranged from 0.02 to 0.18 μg/g, and O-desmethyltramadol concentrations, determined by gas chromatography with nitrogen-specific detection, ranged from 0.4 to 4.3 μg/g. We believe that the addition of the potent mu-receptor agonist O-desmethyltramadol to powdered leaves from Kratom contributed to the unintentional death of the nine cases presented and conclude that intake of Krypton is not as harmless as it often is described on internet websites.
Kratom (Mitragyna speciosa) has been used for medicinal and recreational purposes. It has reported analgesic, euphoric and antitussive effects via its action as an agonist at opioid receptors. It is illegal in many countries including Thailand, Malaysia, Myanmar, South Korea and Australia; however, it remains legal or uncontrolled in the UK and USA, where it is easily available over the Internet. We describe a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. He demonstrated dependence on kratom with withdrawal symptoms consisting of anxiety, restlessness, tremor, sweating and cravings for the substance. A reducing regime of dihydrocodeine and lofexidine proved effective in treating subjective and objective measures of opioid-like withdrawal phenomena, and withdrawal was relatively short and benign. There are only few reports in the literature of supervised detoxification and drug treatment for kratom dependence. Our observations support the idea that kratom dependence syndrome is due to short-acting opioid receptor agonist activity, and suggest that dihydrocodeine and lofexidine are effective in supporting detoxification.
This article reviews evidence of adolescent and young adult drinking motives and their relation to possible consequences over the last 15 years. To this end, a computer-assisted search of relevant articles was conducted. Results revealed that most young people reported drinking for social motives, some indicated enhancement motives, and only a few reported coping motives. Social motives appear to be associated with moderate alcohol use, enhancement with heavy drinking, and coping motives with alcohol-related problems. However, an enormous heterogeneity was found in terms of how motives were measured: 10 to 40 items were grouped into between 2 and 10 dimensions and sometimes the same items occurred under different dimensions. Future studies should therefore use well-defined, theoretically based, homogenous instruments to disentangle cultural from measurement differences across surveys.
We examined the use of Kratom (Mitragyna sp.), a dietary supplement with mu-opioid agonist activity, by members of a cybercommunity who self-treat chronic pain with opioid analgesics from Internet pharmacies. Within one year, an increase in the number of mentions on Drugbuyers.com, a Web site that facilitates the online purchase of opioid analgesics, suggested that members began managing opioid withdrawal with Kratom. This study demonstrates the rapidity with which information on psychoactive substances disseminates through online communities and suggests that online surveillance may be important to the generation of effective opioid analgesic abuse prevention strategies.
The aim of this study was to investigate cross-national differences (1) in the four-dimensional factor structure of drinking motives; (2) in the mean levels of enhancement, coping, social, and conformity motives; and (3) in the association of these motives with adolescent alcohol use, risky single-occasion drinking, and alcohol-related problems.
Confirmatory factor analysis, analysis of variance, and structural equation modeling were applied to sample data from Switzerland (n=5,118; mean age=15.3), Canada (n=2,557; mean age=15.7), and the United States (n=607; mean age=15.7).
The results showed that the four-dimensional factor structure of the Drinking Motives Questionnaire Revised (DMQ-R) was structurally invariant across the three countries. Although the rank order in mean levels of motive endorsement was the same across countries (i.e., highest for social, followed by enhancement, coping, and conformity), the absolute levels of endorsement were highest in the Canadian sample, followed by the Swiss and then the U.S. sample. In all three countries, enhancement and coping motives were positively related to alcohol use and to risky drinking in particular, and coping motives were additionally related to alcohol-related problems.
The results indicate that the DMQ-R is a valid and reliable instrument to assess drinking motives across cultures. It appears therefore that the DMQ-R is an ideal instrument for inclusion in large cross-national surveys and that programs that target motives as a way to reduce risky drinking may be appropriate for different drinking cultures in different geographical locations.
Kratom or Mitragyna speciosa (Korth.) is a medicinal plant of Southeast Asia. As a result of its opioid-like effects, it remains unknown whether consumption of kratom tea is associated with impaired cognitive function. We assessed the cognitive function of 70 regular kratom users and 25 control participants using the Cambridge Neuropsychological Test Automated Battery. Participants performed six neuropsychological tasks that assessed motor, learning and memory, attention and executive function. Relative to control participants, higher consumption (>3 glasses daily or mitragynine doses between 72.5 mg and 74.9 mg) of kratom tea was selectively associated with impaired performance on the Paired Associates Learning task, reflecting deficits in visual episodic memory and new learning. Overall, the performance of kratom users compared to control participants, and the performance of high (>3 glasses per day) as well as low (≤3 glasses per day) kratom using groups, were comparable on all neuropsychological domains. Higher intake of kratom juice (>3 glasses daily) did not appear to impair motor, memory, attention or executive function of regular kratom users.
Ethnopharmacological relevance:
Mitragyna speciosa (Korth.) also known as kratom, is a native medicinal plant of Southeast Asia with opioid-like effects. Kratom tea/juice have been traditionally used as a folk remedy and for controlling opiate withdrawal in Malaysia. Long-term opioid use is associated with depletion in testosterone levels.
Aim of the study:
Since kratom is reported to deform sperm morphology and reduce sperm motility, we aimed to clinically investigate the testosterone levels following long-term kratom tea/juice use in regular kratom users.
Methods:
A total of 19 regular kratom users were recruited for this cross-sectional study. A full-blood test was conducted including determination of testosterone level, follicle stimulating hormone (FSH) and luteinizing hormone (LH) profile, as well as hematological and biochemical parameters of participants.
Results:
We found long-term kratom tea/juice consumption with a daily mitragynine dose of 76.23mg to 94.15mg did not impair testosterone levels, or gonadotrophins, hematological and biochemical parameters in regular kratom users.
Conclusion:
Regular kratom tea/juice consumption over prolonged periods (>2 years) was not associated with testosterone impairing effects in humans.
Background:
Kratom (Mitragyna speciosa) is a psychoactive plant native to Southeastern Asia that is receiving increased international attention as a potential therapeutic agent. While much of the limited scientific research on kratom is focused on its analgesic potential, kratom use also has important risks and benefits in the domain of mental health.
Methods:
We conducted a comprehensive systematic review of all studies on kratom use and mental health published between January 1960 and July 2017.
Results:
Findings indicate kratom's potential as a harm reduction tool, most notably as a substitute for opioids among people who are addicted. Kratom also enhances mood and relieves anxiety among many users. For many, kratom's negative mental health effects - primarily withdrawal symptoms - appear to be mild relative to those of opioids. For some users, however, withdrawal is highly uncomfortable and maintaining abstinence becomes difficult.
Conclusion:
Results inform clinicians working in the mental health and substance use fields, policy-makers, and researchers about the mental health effects of this plant.
Background:
Kratom use in the West has increased recently, yet the prevalence and motives for use among individuals with a history of substance use disorder (SUD) have not been fully examined. Kratom has been documented as a means of treating chronic pain, mitigating drug dependence, and easing withdrawal symptoms, yet it is unclear if substance users are utilizing kratom as a self-medication. Abuse liability, side effects, and overall appeal of kratom remain uncertain.
Methods:
In April 2017, an anonymous survey regarding kratom use and motivations was completed by clients enrolled in a 12-Step-oriented residential program. 500 respondents with a self-reported history of SUD completed the survey.
Results:
20.8% of respondents endorsed lifetime kratom use and 10.2% reported past-12-month use. Kratom-users were younger (=32.1 vs. 35.9, p<0.001) and were more versatile substance users. A majority (68.9%) of kratom-users reported having used the drug as a means of reducing or abstaining from non-prescription opioids (NPO) and/or heroin, and 64.1% reported using kratom as a substitute for NPO/heroin. 18.4% of kratom-users reported using the drug due to a disability or chronic pain. One-third of kratom-users stated that kratom was a helpful substance and that they would try it again. However, kratom was not preferred and was indicated as having less appeal than NPO, heroin, amphetamines, and Suboxone.
Conclusions:
Among substance users, kratom use may be initiated for a variety of reasons, including as a novel form of harm-reduction or drug substitution, particularly in the context of dependence and withdrawal from other substances.
Background:
Kratom preparations have raised concerns of public health and safety in the US. Investigation into the demographics, perceived beneficial and detrimental effects of Kratom as well as common doses and purposes of its use are important to properly evaluate its potential health impact.
Methods:
An anonymous cross-sectional online survey was conducted in October 2016 of 10,000 current Kratom users through available social media and online resources from the American Kratom Association. A total of 8049 respondents completed the survey.
Results:
Kratom is primarily used by a middle-aged (31-50 years), middle-income ($35,000 and above) population for purposes of self-treating pain (68%) and emotional or mental conditions (66%). Kratom preparations present with a dose-dependent effect with negative effects, which were primarily gastrointestinal related including nausea and constipation, mainly presenting at high (5g or more/dose) and more frequent (22 or more doses/week) dosing.
Conclusions:
Kratom shows a dose-dependent opioid-like effect providing self-reported perceived beneficial effects in alleviating pain and relieving mood disorders. Kratom was primarily used for self-treatment of pain, mood disorders, and withdrawal symptoms associated with prescription opioid use.
Ethnopharmacological relevance:
The genus Mitragyna (Rubiacaeae) has been traditionally used in parts of Africa, Asia and Oceania. In recent years, there has been increased interest in species of Mitragyna with the introduction of products to western markets and regulatory uncertainty.
Aim of the study:
This paper reviewed the traditional ethnomedicinal uses of leaves for species belonging to the genus Mitragyna with reference to the botany and known chemistry in order to highlight areas of interest for products currently being sold as kratom.
Materials and methods:
A literature search was conducted using Web of Science, Google Scholar, the Royal Museum for Central Africa, Internet Archive, Hathi Trust, and Biodiversity Heritage Library search engines in the spring of 2015, fall of 2016 and winter of 2017 to document uses of bark, leaf and root material.
Results:
Leaves of M. speciosa (kratom) had the most common documented ethnomedicinal uses as an opium substitute or remedy for addiction. Other species of Mitragyna were reportedly used for treating pain, however the mode of preparation was most often cited as topical application. Other uses of Mitragyna included treatment of fever, skin infections, and as a mild anxiolytic.
Conclusions:
Mitragyna species have been used medicinally in various parts of the world and that there is significant traditional evidence of use. Modern products that include formulations as topical application of liniments, balms or tinctures may provide effective alternatives for treatment of certain types of pains. Future research is required to establish safety and toxicology limits, medicinal chemistry parameters and the potential for different physiological responses among varying genetic populations to support regulatory requirements for Mitragyna spp.
Two cases of fatalities are reported of which the recreational use of Mitragyna speciosa (“kratom”) could be confirmed. One of these cases presents with one of the highest postmortem mitragynine concentrations published to date. Our results show that even extremely high mitragynine blood concentrations following the consumption of kratom do not necessarily have to be the direct cause of death in such fatalities as a result of an acute overdose. The two cases are compared with regard to the differences in mitragynine concentrations detected and the role of mitragynine in the death of the subjects. Irrespective of the big differences in mitragynine concentrations in the postmortem blood samples, mitragynine was not the primary cause of death in either of the two cases reported here. Additionally, by rough estimation, a significant difference in ratio of mitragynine to its diastereomers in the blood and urine samples between the two cases could be seen.
Kratom (Mitragyna speciosa) is a plant consumed throughout the world for its stimulant effects and as an opioid substitute (1). It is typically brewed into a tea, chewed, smoked, or ingested in capsules (2). It is also known as Thang, Kakuam, Thom, Ketum, and Biak (3). The Drug Enforcement Administration includes kratom on its Drugs of Concern list (substances that are not currently regulated by the Controlled Substances Act, but that pose risks to persons who abuse them), and the National Institute of Drug Abuse has identified kratom as an emerging drug of abuse (3,4). Published case reports have associated kratom exposure with psychosis, seizures, and deaths (5,6). Because deaths have been attributed to kratom in the United States (7), some jurisdictions have passed or are considering legislation to make kratom use a felony (8). CDC characterized kratom exposures that were reported to poison centers and uploaded to the National Poison Data System (NPDS) during January 2010-December 2015. The NPDS is a national database of information logged by the country's regional poison centers serving all 50 United States, the District of Columbia, and Puerto Rico and is maintained by the American Association of Poison Control Centers. NPDS case records are the result of call reports made by the public and health care providers.
Introduction:
The objective of the paper was to highlight the differences in the traditional and non-traditional users of kratom in the South East Asian and Western contexts.
Method:
A literature survey of published kratom studies among humans was conducted. Forty published studies relevant to the objective were reviewed.
Results:
Apart from the differences in the sources of supply, patterns of use and social acceptability of kratom within these two regions, the most interesting finding is its evolution to a recreational drug in both settings and the severity of the adverse effects of kratom use reported in the West. While several cases of toxicity and death have emerged in the West, such reports have been non-existent in South East Asia where kratom has had a longer history of use. We highlight the possible reasons for this as discussed in the literature. More importantly, it should be borne in mind that the individual clinical case-reports emerging from the West that link kratom use to adverse reactions or fatalities frequently pertained to kratom used together with other substances. Therefore, there is a danger of these reports being used to strengthen the case for legal sanction against kratom. This would be unfortunate since the experiences from South East Asia suggest considerable potential for therapeutic use among people who use drugs.
Conclusion:
Despite its addictive properties, reported side-effects and its tendency to be used a recreational drug, more scientific clinical human studies are necessary to determine its potential therapeutic value.
Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use of these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there is a longstanding interest in the development of new opioid analgesics with improved therapeutic profiles. The alkaloids of the Southeast Asian plant Mitragyna speciosa, represented by the prototypical member mitragynine, are an unusual class of opioid receptor modulators with distinct pharmacological properties. Here we describe the first receptor-level functional characterization of mitragynine and related natural alkaloids at the human mu-, kappa-, and delta-opioid receptors. These results show that mitragynine and the oxidized analogue 7-hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. We also show that mitragynine and 7-hydroxymitragynine are G-protein-biased agonists of the mu-opioid receptor, which do not recruit β-arrestin following receptor activation. Therefore, the Mitragyna alkaloid scaffold represents a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles. Also presented is an enantioselective total synthesis of both (-)-mitragynine and its unnatural enantiomer, (+)-mitragynine, employing a proline-catalyzed Mannich-Michael reaction sequence as the key transformation. Pharmacological evaluation of (+)-mitragynine revealed its much weaker opioid activity. Likewise, the intermediates and chemical transformations developed in the total synthesis allowed the elucidation of previously unexplored structure-activity relationships (SAR) within the Mitragyna scaffold. Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids.
Given increasing marijuana use and abuse among young adults in the United States and the associated physical and mental health consequences, it is important to improve our understanding of factors that may contribute to problematic marijuana use. A convergence of theory and research underscores the relevance of particular marijuana use motives generally, and coping-related motives specifically, in enhancing risk for marijuana use problems. Distress tolerance is a transdiagnostic emotion vulnerability factor that may relate to coping-related motives for marijuana use. The current study was designed to further explore this relationship within a treatment-seeking sample of young adults (Mage = 24.40; SD = 2.06 years). Results were consistent with hypotheses, suggesting distress tolerance is related to coping motives for marijuana use within this treatment-seeking sample, even after accounting for a number of theoretically relevant covariates. Theoretical and applied implications of distress tolerance as it relates to coping motives for marijuana use as treatment targets are discussed.
Motives for marijuana use are important predictors of problematic outcomes associated with marijuana use. Most measures, to date, were developed by adapting alcohol motives measures. However, the Comprehensive Marijuana Motives Questionnaire (CMMQ) was created using a bottom-up approach to evaluate twelve distinct motives for use. The CMMQ was developed and validated in a normative college population. As such, no known study has evaluated the factor structure and utility of the CMMQ in a heavy-using, high school student population. The current study utilized a sample of 252 heavy marijuana-using high school students recruited for a combination motivational enhancement/cognitive behavioral intervention. Results from baseline measures indicated that the factor structure of the CMMQ was maintained in this population. Results from multiple regression analyses revealed distinct relationships with measures of negative consequences of use, including indices of marijuana use, marijuana-related problems, self-efficacy, and internalizing and externalizing symptoms. In particular, the coping motive was associated with several negative outcomes, which is consistent with previous marijuana and alcohol motives literature. Results suggest that the CMMQ may be useful in assessing marijuana motives among heavy marijuana-using adolescents.
Background:
Krathom is currently the most popular illicit substance in use in southern Thailand. Research regarding its effects and health impacts is scarce. This study explored the pattern of krathom use and users' perceptions of the consequences of its use.
Methods:
An in-depth qualitative interview. A group of 34 self-identified regular users, occasional users, non-users and ex-users of krathom was used in this study. Health volunteer as a key-contact person helped the researcher to invite villagers to participate in the study using snowballing technique. The process of data analysis was guided by Strauss and Corbin's grounded theory.
Results:
The core category, 'Understanding krathom use', was generated from three inter-related categories: (i) reasons for continuing krathom use, (ii) the way of applying krathom, and (iii) perceiving positive and realizing the negative effects of krathom use and their 18 subcategories.
Conclusions:
The study findings reveal the importance of considering krathom use from the perspective and belief of the villagers. Krathom is addictive with its own characteristic symptoms and signs. The results provide support for policy interventions to control the availability of krathom according to the community context. In addition, krathom misuse by adolescents must be considered.
A new indole alkaloid, 7-hydroxyspeciociliatine (1), was isolated from the fruits of Malaysian Mitragyna speciosa Korth., together with 11 known indole and oxindole alkaloids (3–13). The structure of the new compound was determined by spectroscopic analysis and chemical conversion. The opioid agonistic activity of the new alkaloid was investigated in guinea-pig ileum experiments. The compound was found to have a weak stimulatory effect on -opioid receptors.
Kratom (Mitragyna speciosa) is a common medical plant in Thailand and is known to contain mitragynine as the main alkaloid. According to an increase in published reports and calls at German poison control centers, it has been used more frequently as a drug of abuse in the western hemisphere during the last couple of years. Despite this increase, reports of severe toxicity are rare within the literature.
We describe a case of a young man who presented with jaundice and pruritus after intake of kratom for 2 weeks in the absence of any other causative agent. Alkaloids of M. speciosa were detected in the urine.
While M. speciosa is gaining in popularity among illicit drug users, its adverse effects remain poorly understood. This is the first published case of intrahepatic cholestasis after kratom abuse.
Mitragyna speciosa (Kratom in Thai), a Thai medical plant, is misused as herbal drug of abuse. Besides the most abundant alkaloids mitragynine (MG) and paynantheine (PAY), several other alkaloids were isolated from Kratom leaves, among them the third abundant alkaloid is speciogynine (SG), a diastereomer of MG. The aim of this present study was to identify the phase I and II metabolites of SG in rat urine after the administration of a rather high dose of the pure alkaloid and then to confirm these findings using human urine samples after Kratom use. The applied liquid chromatography coupled to low- and high-resolution mass spectrometry (LC-HRMS-MS) provided detailed information on the structure in the MS(n) mode particularly with high resolution. For the analysis of the human samples, the LC separation had to be improved markedly allowing the separation of SG and its metabolites from its diastereomer MG and its metabolites. In analogy to MG, besides SG, nine phase I and eight phase II metabolites could be identified in rat urine, but only three phase I and five phase II metabolites in human urine. These differences may be caused by the lower SG dose applied by the user of Kratom preparations. SG and its metabolites could be differentiated in the human samples from the diastereomeric MG and its metabolites comparing the different retention times determined after application of the single alkaloids to rats. In addition, some differences in MS(2) and/or MS(3) spectra of the corresponding diastereomers were observed.
This study evaluated the prediction that coping motives for marijuana use would mediate the relation between anxiety sensitivity and a marijuana dependence diagnosis after controlling for other co-occurring marijuana use motives. Participants were 136 current marijuana users (47.1% women; M(age)= 21.9, SD = 7.2). Results were consistent with a mediational effect, with the relation between anxiety sensitivity and marijuana dependence being explained by the addition of coping motives into the model. These results provide novel information related to the putative explanatory role of coping motives for marijuana use in the relation between anxiety sensitivity and marijuana dependence.
Ketum (krathom) has been mentioned in the literature as a traditional alternative to manage drug withdrawal symptoms though there are no studies indicating its widespread use for this purpose. This study examines the reasons for ketum consumption in the northern areas of peninsular Malaysia where it is widely used.
A cross-sectional survey of 136 active users was conducted in the northern states of Kedah and Penang in Malaysia. On-site urine screening was done for other substance use.
Ketum users were relatively older (mean 38.7 years) than the larger substance using group. Nearly 77% (104 subjects) had previous drug use history, whilst urine screening confirmed 62 subjects were also using other substances. Longer-term users (use >2 years) had higher odds of being married, of consuming more than the average three glasses of ketum a day and reporting better appetite. Short-term users had higher odds of having ever used heroin, testing positive for heroin and of using ketum to reduce addiction to other drugs. Both groups used ketum to reduce their intake of more expensive opiates, to manage withdrawal symptoms and because it was cheaper than heroin. These findings differ from those in neighbouring Thailand where ketum was used primarily to increase physical endurance.
No previous study has shown the use of ketum to manage opioid withdrawal symptoms except for a single case reported in the US. Ketum was described as affordable, easily available and having no serious side effects despite prolonged use. It also permitted self-treatment that avoids stigmatisation as a drug dependent. The claims of so many subjects on the benefits of ketum merits serious scientific investigation. If prolonged use is safe, the potential for widening the scope and reach of substitution therapy and lowering its cost are tremendous, particularly in developing countries.
The Thai medicinal plant Mitragyna speciosa (Kratom in Thai) is misused as a herbal drug of abuse. During studies on the main Kratom alkaloid mitragynine (MG) in rats and humans, several dehydro analogs could be detected in urine of Kratom users, which were not found in rat urine after administration of pure MG. Questions arose as to whether these compounds are formed from MG only by humans or whether they are metabolites formed from the second abundant Kratom alkaloid paynantheine (PAY), the dehydro analog of MG. Therefore, the aim of the presented study was to identify the phase I and II metabolites of PAY in rat urine after administration of the pure alkaloid. This was first isolated from Kratom leaves. Liquid chromatography–linear ion trap mass spectrometry provided detailed structure information of the metabolites in the MSn mode particularly with high resolution. Besides PAY, the following phase I metabolites could be identified: 9-O-demethyl PAY, 16-carboxy PAY, 9-O-demethyl-16-carboxy PAY, 17-O-demethyl PAY, 17-O-demethyl-16,17-dihydro PAY, 9,17-O-bisdemethyl PAY, 9,17-O-bisdemethyl-16,17-dihydro PAY, 17-carboxy-16,17-dihydro PAY, and 9-O-demethyl-17-carboxy-16,17-dihydro PAY. These metabolites indicated that PAY was metabolized via the same pathways as MG. Several metabolites were excreted as glucuronides or sulfates. The metabolism studies in rats showed that PAY and its metabolites corresponded to the MG-related dehydro compounds detected in urine of the Kratom users. In conclusion, PAY and its metabolites may be further markers for a Kratom abuse in addition of MG and its metabolites.
Figure
Isolation of paynantheine from kratom leaves; high-resolution mass spectrum of the glucuronide of its 9-O-demethyl metabolite, and paynantheine structure with marked sides of biotransformation.