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Kratom (or Ketum) is a psychoactive plant preparation used in Southeast Asia. It is derived from the plant Mitragyna speciosa Korth. Kratom as well as its main alkaloid, mitragynine, currently spreads around the world. Thus, addiction potential and adverse health consequences are becoming an important issue for health authorities. Here we reviewed the available evidence and identified future research needs. It was found that mitragynine and M. speciosa preparations are systematically consumed with rather well defined instrumentalization goals, e.g. to enhance tolerance for hard work or as a substitute in the self-treatment of opiate addiction. There is also evidence from experimental animal models supporting analgesic, muscle relaxant, anti-inflammatory as well as strong anorectic effects. In humans, regular consumption may escalate, lead to tolerance and may yield aversive withdrawal effects. Mitragynine and its derivatives actions in the central nervous system involve μ-opioid receptors, neuronal Ca2+ channels and descending monoaminergic projections. Altogether, available data currently suggest both, a therapeutic as well as an abuse potential.
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... Kratom leaves contain approximately 40 types of alkaloids (10). Mitragynine is the most abundant indole alkaloid (11) consisting of 66% of the alkaloids content (11). 7-Hydroxymitragynine (7-HMG), an Ivyspring International Publisher active metabolite of mitragynine, is made up 0.04% of the alkaloid content of kratom leaves extracts (11)(12)(13). ...
... Kratom leaves contain approximately 40 types of alkaloids (10). Mitragynine is the most abundant indole alkaloid (11) consisting of 66% of the alkaloids content (11). 7-Hydroxymitragynine (7-HMG), an Ivyspring International Publisher active metabolite of mitragynine, is made up 0.04% of the alkaloid content of kratom leaves extracts (11)(12)(13). ...
... Mitragynine is the most abundant indole alkaloid (11) consisting of 66% of the alkaloids content (11). 7-Hydroxymitragynine (7-HMG), an Ivyspring International Publisher active metabolite of mitragynine, is made up 0.04% of the alkaloid content of kratom leaves extracts (11)(12)(13). 7-HMG is formed as the break down product of mitragynine by the activity of CYP3A4 (14). In addition, 7-HMG may be formed post-harvest in kratom products that possibly contributing to increased reports of kratom toxicity in the Western world (14). ...
Article
Background: Mitragyna speciosa Korth or Kratom is widely used traditionally for its medicinal values. The major alkaloid content of kratom leaves is mitragynine, which binds to opioid receptors to give opioid-like effects. This study aimed to analyse the brain proteome of animals that displayed addictive behaviors. Design and Methods: Six groups (n=6-8) of rats made up of negative control, positive control using morphine (10 mg/kg), and treatment groups at low (1mg/kg) and high doses of mitragynine (30 mg/kg) for 1 and 4 days. The rats' behaviors were evaluated and subsequently the rats' brains were harvested for proteomic analysis that was performed by using 2D gel electrophoresis and LC/MS/MS. Results: The rats developed physical dependence only on day 4 following morphine and mitragynine (1 and 30mg/kg) treatments. Among the proteins that were up-regulated in treatment groups were four calcium-binding proteins, namely calretinin, F-actin, annexin A3 and beta-centractin. Conclusions: Upregulation of calretinin acted as low Ca2+ buffering upon the blockage of Ca2+ ion channel by mitragynine in the brain, which subsequently caused a reduction of GABA released and inversely increased the dopamine secretions that contributed to dependence indicators.
... The molecular structures of the tested compounds were mitragynine, paynantheine, speciofoline, mitraphylline, speciophylline, corynoxineB, isomitraphylline, mitraciliatine, corynoxineA, corynantheidine, isorhynchophylline, mitrafoline, ajmalicine, speciociliatine, isospeciofoline, mitragynaline, 7-hydroxymitragynine, rhynchophylline, and speciogynine. 18 ...
... This compound contained <1% of the alkaloid fraction of Mitragyna speciosa leaves. 18 This plant alkaloid fraction has anticancer activity in nasopharyngeal cancer with an IC 50 value of 32.16 ± 0.94 µg/ml. 34 Mitrafoline is a compound belonging to the indole alkaloid group. ...
Article
Full-text available
Breast cancer is one of the major universal health problems affecting more than two million cases per year. Estrogen receptor alpha (ERα) and P53 are common targets for the treatment of breast cancer and are primarily involved in cell proliferation. The function of p53 protein is regulated by direct binding to MDM2 protein. Therefore, inhibition of p53-MDM2 interaction leads to reactivating p53 activity. Alkaloid compounds generally have potential anticancer effect. Alkaloid compound from Mitragyna speciosa have the potential for anticancer
... Apart from Thailand and Malaysia, Bhutan, Finland, Lithuania, Denmark, Poland, Sweden, Australia, and Myanmar have kratom under control or regulation [5]. Prior to 2016, only five states in the United States regulated kratom, and the DEA (US Drug Enforcement Administration) classified it as a drug of concern [11]. ...
... Moreover, speciociliatine was found as being the most abundant alkaloid detected. Although these additional molecules are unlikely to be psychoactive [5,78], they may be useful indicators of kratom usage, especially considering a recent study indicating that they are more stable than mitragynine and 7-hydroxymitragynine [76]. Nevertheless, the use of the alkaloid from kratom as a detection marker can only indicate that such a person had consumed kratom, and it is well known that many consume kratom for medicinal purposes. ...
... [5]. This plant has been used in local folklore medicine, especially in Malay traditional medicine, to treat diseases, such as fever, malaria, diarrhoea, cough, and expulsing worms [6,7]. ...
Article
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Mitragynine and its congeners are one of the major phytoconstituents present in Mitragyna speciosa Korth. (ketum) leaves and a well-known factor that contributes to ketum’s pharmacological activities. This study describes the usage of a green extraction method to yield botanical leaf extracts of ketum. The leaf extracts were assessed for mitragynine content, total phenolic and flavonoid content, and cytotoxicities. The Ultrasound Assisted Extraction (UAE) method showed a varying dry yield of the extracts (0.22–1.92 g) that were obtained with solvents of variable polarities. However, the mitragynine content was consistent among the organic solvent extracts (7.22–9.40%). This method calls for a minimal extraction solvent volume (solid to solvent ratio, 1:30) and a shorter extraction period (20 min). Of the solvents tested, the methanolic extract showed the highest content of total phenolic (419.50 ± 2.50 GAE mg/g) and flavonoids (177.33 ± 3.00 QE mg/g). The extract was nontoxic towards kidney (HEK-293) and Chang liver (HeLa) cell lines. Analysis via UHPLC-ESI-QTOF-MS/MS made it possible to identify mitragynine congeners, such as mitragynine, paynantheine, and speciociliatine, in the leaves extract. In conclusion, the UAE method using methanol as the extraction solvent provides a noncytotoxic ketum botanical extract for future preclinical and clinical studies.
... Kratom or Mitragyna speciosa is a traditional herbal medicine in Southeast Asia, particularly in rural areas of Thailand and Malaysia (Hassan et al., 2013). Due to its stimulant and opioid-like effects, it was placed under schedule 5 of the Thai Narcotics Act, making it illegal to sell or possess kratom in the past. ...
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Background Kratom is a psychoactive plant used to enhance productivity among laborers in Southeast Asian countries. Previous findings from in vitro research of mitragynine, a major component of kratom, suggested a possible risk of heart function abnormality. However, the cardiac autonomic function in long-term kratom users with chewing forms has never been studied. This study aimed to investigate heart rate variability (HRV) indices of cardiac autonomic function in long-term kratom chewers (LKC), compared to the control levels, and also to examine the correlation between HRV indices and relevant kratom use factors. Method A total number of 50 participants consisted of LKC ( n = 31) who regularly chewed fresh kratom leaves for at least 2 years and demographically matched control subjects ( n = 19). Resting electrocardiogram (ECG) signals were recorded from subjects for 3 min to analyze the ultrashort HRV in the frequency domain. The normalized low frequency (LFn) and high frequency (HFn) were chosen to be the HRV indices to evaluate cardiac autonomic function. The comparison of HRV indices between groups and the correlation between HRV indices and duration and quantity of kratom use was further conducted in statistical analysis. Results The LKC significantly increased LFn together with enhanced HFn compared to the control group tested, indicating that LKC changed cardiac autonomic function with parasympathetic dominance. Furthermore, no significant correlation between the HRV indices and the duration and quantity of kratom use was found, suggesting that the HRV indices were not relevant to these factors. The present study provided scientific-based evidence of cardiac autonomic modulation in long-term kratom chewers. LFn and HFn may be promising cardiac autonomic indicators for monitoring health outcomes in LKC.
Article
Kratom has caught the attention of governments, policymakers, and academicians due to its unique characteristics. This paper explores the scholarly works related to the different aspects of Kratom to elucidate its research progress and identify future research agendas. We reviewed existing publications on Kratom using a bibliometric methodology. By analyzing 431 scientific publications, we identified publication sources, document analysis, countries analysis, and research keywords, which helped us understand the research locus on Kratom. After reviewing the publications, we discovered significant disagreements in categorizing and defining Kratom amongst authors based on their nationalities. We also showed the knowledge structure of existing publications via thematic analysis, illustrating that the studies focused on the opioid nature of Kratom. Also, drug abuse-related issues evolved as the motor theme of research, while other aspects are prevalent as niche or emerging research themes. This paper contributes to the literature by providing a broad idea of existing literature and offering a comprehensive outlook on Kratom, which could be helpful for policy formulation in the future.
Conference Paper
Kratom leaves (Mitragyna speciosa Korth) have been used by people in West Kalimantan, especially Kapuas Hulu District, as local culture, for traditional medicine. This research was conducted to obtain facts and data on utilization and complaints due to the use of kratom leaves in local culture by the people of Kapuas Hulu Regency. Data obtained by interview using a questionnaire and the determination of the respondents is done by snowball. The relationship between period, dose and frequency of kratom leaf consumption and complaints was searched statistically using the chi-quadrate. It was found that 152 respondents who consumed kratom leaves. The main reason respondents consume kratom leaves to overcome fatigue or get stamina (49%) and to treat illness 25%. Generally, 46% of respondents consume kratom leaves for less than 1 year, although 25% of them are more than 5 years. Most of the respondents consumed kratom leaf powder at a dose of ¼ teaspoon (0.5 g) with the highest frequency once a day (27.94%). Chi-square analysis showed that there was no very significant relationship between the period of drinking kratom leaves and complaints, but there was a very significant relationship between the dose of kratom leaf consumption and complaints and between the frequency of drinking kratom leaves and complaints. There were no complaints such as symptoms of narcotics and drug users. Generally, respondents stated that they did not experience complaints 93.42%. About 6.58% of complaints were feeling tired, drowsy and achy.
Article
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.
Article
Mitragyna speciosa Korth or ketum or kratom has long been used by local people in Thailand and Malaysia to treat various types of diseases and to boost energy. There is lack of information available on the effect of M. speciosa Korth in learning and memory function, therefore this study was conducted to understand its effect using a cellular model (hippocampus). The objective of this study was to delineate the effect of M. speciosa Korth standardized methanol extract (MS), we used extracellular recording in rat hippocampal slices in vitro. Acute hippocampal slices were prepared from 4 weeks-old male Sprague dawley rats. Field excitatory post-synaptic potentials (fEPSP) were investigated after the application of test materials in concentrations of 0.0001, 0.001, 0.005, 0.01, 0.05 and 0.1% dissolved in 0.1% DMSO. The 50% inhibitory concentration (IC50) of test material was then calculated. Superfusion of MS (all concentrations) produced irreversible fEPSP amplitude reduction with an IC50 of 0.008%. The same concentration of MS (0.008%) prevented the induction of long-term potentiation (LTP) and induced only short-term potentiation (STP) in CA1 neurons. In the CA1 region of the hippocampus, reduced concentration-dependently glutamatergic transmission and blocked LTP at the IC50.