Displaying publications 1 - 20 of 90 in total

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  1. Hamid HA, Ramli AN, Yusoff MM
    Front Pharmacol, 2017;8:96.
    PMID: 28293192 DOI: 10.3389/fphar.2017.00096
    Depression is the most common illness observed in the elderly, adults, and children. Antidepressants prescribed are usually synthetic drugs and these can sometimes cause a wide range of unpleasant side effects. Current research is focussed on natural products from plants as they are a rich source of potent new drug leads. Besides Hypericum perforatum (St. John's wort), the plants studied include Passiflora incarnata L. (passion flower), Mitragyna speciosa (kratom), Piper methysticum G. Forst (kava) and Valeriana officinalis L. Harman, harmol, harmine, harmalol and harmaline are indole alkaloids isolated from P. incarnata, while mitragynine is isolated from M. speciosa. The structure of isolated compounds from P. methysticum G. Forst and V. officinalis L. contains an indole moiety. The indole moiety is related to the neurotransmitter serotonin which is widely implicated for brain function and cognition as the endogenous receptor agonist. An imbalance in serotonin levels may influence mood in a way that leads to depression. The moiety is present in a number of antidepressants already on the market. Hence, the objective of this review is to discuss bioactive compounds containing the indole moiety from plants that can serve as potent antidepressants.
    Matched MeSH terms: Mitragyna
  2. Said IM, Chun NC, Houghton PJ
    Planta Med, 1991 Aug;57(4):398.
    PMID: 17226178
    Matched MeSH terms: Mitragyna
  3. Leong Bin Abdullah MFI, Mohamad MA, Abdul Rahman NN
    J Relig Health, 2021 Apr;60(2):841-853.
    PMID: 31069602 DOI: 10.1007/s10943-019-00830-w
    This paper aimed to summarize kratom's psychological effects on users and the Islamic views on kratom use. A literature survey of published kratom studies, teachings based on the holy Qur'an, the Sunnah, and views of several Islamic scholars based on qualitative methodology through text analysis was conducted. The results demonstrated that despite its beneficial therapeutic effects, the harm induced by kratom outweighs its benefits. We concluded that kratom use for medicinal purposes is only warranted if useful constituent mitragynine can be extracted and used on its own, and if more rigorous human studies demonstrated good safety profile and efficacy of mitragynine for therapeutic purposes.
    Matched MeSH terms: Mitragyna*
  4. Haron M, Ismail S
    Pharmacognosy Res, 2014 Oct-Dec;7(4):341-9.
    PMID: 26692748 DOI: 10.4103/0974-8490.159580
    BACKGROUND: Glucuronidation catalyzed by uridine 5'- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.
    OBJECTIVE: The objective was to evaluate the inhibitory potentials of mitragynine, 7-hydroxymitragynine, ketamine and buprenorphine, respectively on 4-methylumbelliferone (4-MU) glucuronidation in rat liver microsomes, human liver microsomes and recombinant human UGT1A1 and UGT2B7 isoforms.
    MATERIALS AND METHODS: The effects of the above four compounds on the formation of 4-MU glucuronide from 4-MU by rat liver microsomes, human liver microsomes, recombinant human UGT1A1 and UGT2B7 isoforms were determined using high-performance liquid chromatography with ultraviolet detection.
    RESULTS: For rat liver microsomes, ketamine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.21 ± 1.51 μM followed by buprenorphine with an IC50 value of 73.22 ± 1.63 μM. For human liver microsomes, buprenorphine strongly inhibited 4-MU glucuronidation with an IC50 value of 6.32 ± 1.39 μM. For human UGT1A1 isoform, 7-hydroxymitragynine strongly inhibited 4-MU glucuronidation with an IC50 value of 7.13 ± 1.16 μM. For human UGT2B7 isoform, buprenorphine strongly inhibited 4-MU glucuronidation followed by 7-hydroxymitragynine and ketamine with respective IC50 values of 5.14 ± 1.30, 26.44 ± 1.31, and 27.28 ± 1.18 μM.
    CONCLUSIONS: These data indicate the possibility of drug-drug interaction if 7-hydroxymitragynine, ketamine, and buprenorphine are co-administered with drugs that are UGT2B7 substrates since these three compounds showed significant inhibition on UGT2B7 activity. In addition, if 7-hydroxymitragynine is to be taken with other drugs that are highly metabolized by UGT1A1, there is a possibility of drug-drug interaction to occur.
    KEYWORDS: 4-methylumbelliferone; 7-hydroxymitragynine; buprenorphine; glucuronidation; ketamine; mitragynine
    Matched MeSH terms: Mitragyna
  5. Sabetghadam A, Ramanathan S, Mansor SM
    Pharmacognosy Res, 2010 May;2(3):181-5.
    PMID: 21808563 DOI: 10.4103/0974-8490.65514
    Mitragyna speciosa Korth is a medicinal plant indigenous to Thailand and Malaysia and has been known for its narcotic and coca-like effects. Many studies have been performed on the antinociceptive effect of the plant extracts of Thai origin; however, limited studies have been reported till date on M. speciosa extracts of Malaysian origin. Various concentrations of alkaloid (5-20 mg/kg), methanolic (50-200 mg/kg), and aqueous (100-400 mg/kg) extracts of Malaysian M. speciosa leaves were prepared and orally administered to nine groups of rats. Morphine (5 mg/kg, s.c.) and aspirin (300 mg/kg, p.o.) were used as control. Antagonism of the antinociceptive activity was evaluated by pretreatment with naloxone at a dose of 2 mg/kg (i.p.). Results showed that oral administration of the alkaloid (20 mg/kg), methanolic (200 mg/kg), and aqueous (400 mg/kg) extracts significantly prolonged the latency of nociceptive response compared with control groups in both hot plate and tail flick tests (P < 0.05). Antinociceptive action of the alkaloid (20 mg/kg), methanolic (200 mg/kg), and aqueous (400 mg/kg) extracts was significantly blocked by naloxone. In conclusion, these results suggest the presence of antinociceptive effect in various extracts of Malaysian M. speciosa leaves. In addition, the antinociceptive effective doses vary depending on the type of solvents used for extraction.
    Matched MeSH terms: Mitragyna
  6. Ilmie MU, Jaafar H, Mansor SM, Abdullah JM
    Front Neurosci, 2015;9:189.
    PMID: 26136645 DOI: 10.3389/fnins.2015.00189
    Mitragyna speciosa Korth, or better known as ketum, has long been used by traditional folk around Southeast Asia to prevent fatigue from working under hot tropical weather and as a replacement of opium, which can then cause addiction. To date, no findings have been reported of the toxic effect of ketum subchronically (28 days). Hence, the aim of this study was to investigate the toxicity of subchronic effect of standardized methanolic extract of ketum (SMEMS) in Sprague-Dawley rats. Rats were orally administered with 100, 200, and 500 mg/kg of SMEMS for 28 days. Body weights were recorded daily. They were terminated at day 28 to obtain data for hematology, biochemistry, and histopathology of the brain, liver, kidney, lung, heart, sciatic nerve, and spinal cord. The SMEMS affected body weight compared to control group. Biochemistry findings showed that liver and kidney were affected with the abnormal values in AST, creatinine, globulin, glucose, total protein, and urea. However, SMEMS produced toxic effect more to liver, kidney, and lung than other organs as observed histopathologically. The results suggested subchronic exposure of ketum is toxic to the physiology of the animals.
    Matched MeSH terms: Mitragyna
  7. Ilmie MU, Mansor SM, Abdullah JM
    Malays J Med Sci, 2015 Dec;22(Spec Issue):45-51.
    PMID: 27006637 MyJurnal
    BACKGROUND: Mitragyna speciosa (MS) or ketum is primarily found in Southeast Asia, particularly in northern Malaysia and Thailand. The medicinal value of this plant has attracted significant attention from both herbal medicine practitioners and scientists worldwide. Despite having illegal consumption status, the plant merits study. We conducted a series of experiments to test our hypothesis that ketum impairs both learning and memory in rats.
    METHODS: Ketum leaves were extracted using methanol and standardised for the amount of its pure compound, mitragynine. Rats were divided into groups for a passive avoidance task and long-term potentiation (LTP) extracellular recording. In the extracellular recording condition, rats were grouped into control, MS100 (100 mg/kg of ketum extract), MS200 (200 mg/kg of ketum extract), and MS500 (500 mg/kg of ketum extract) groups. An additional group that received morphine was included in the passive avoidance task (10 mg/kg), and there were six animals per group. Rats received daily treatments orally for 28 days for both experiments.
    RESULT: Using a passive avoidance task, our data revealed that the rats' memory significantly increased with increasing doses of MS compared to the morphine-treated group. Our findings from LTP recordings showed that LTP was fully blocked by the higher doses of MS.
    CONCLUSION: We speculate on the possibility that additional factors were involved in the passive avoidance task because it was an in vivo animal study, while the LTP experiment solely involved brain slices.
    Matched MeSH terms: Mitragyna
  8. Halim SA, Low JH, Chee YC, Alias MR
    Epilepsy Behav, 2021 08;121(Pt A):108057.
    PMID: 34052638 DOI: 10.1016/j.yebeh.2021.108057
    We report a case series of young adults who were admitted to hospital with seizures after regular kratom beverage consumption. This study aimed to determine kratom consumption habits and seizure characteristics and to explore whether chronic kratom ingestion without concomitant drug abuse leads to recurrent seizure or epilepsy. All patients underwent blood investigations, a brain computed tomography (CT) scan, electroencephalography, and urine testing for mitragynine and drug toxicology. Eleven participants who had a positive urine mitragynine test were included in the study. The longest duration of kratom consumption was 84 months: - most drank more than eight times per month (>200 mL/drink). Seizure developed within 10 minutes or up to 72 hours post-ingestion. Seizure occurred one to three times per year in most cases. Four patients had a focal to bilateral tonic-clonic seizure whereas the remaining participants had a generalized tonic-clonic seizure. Four patients mixed kratom with diphenhydramine syrup, and one patient took methamphetamine. Two patients had positive urine results for recreational drugs (opioid and amphetamine). This study provided indirect evidence that chronic kratom use with or without concomitant drug abuse can cause recurrent seizures in susceptible individuals, which may progress to epilepsy or require antiepileptic medication.
    Matched MeSH terms: Mitragyna*
  9. Jasim RK, Singh D, Gam LH
    Biotechnol Appl Biochem, 2023 Apr;70(2):707-715.
    PMID: 35931067 DOI: 10.1002/bab.2392
    Kratom (Mitragyna speciosa Korth) has been used traditionally in Southeast Asia for its therapeutic properties. The major alkaloid of kratom, mitragynine, binds to opioid receptors to give opioid-like effects that causes addiction. In our previous study, we have identified AZ122 as a unique biomarker in habitual or regular kratom users through analysis of their urinary protein profiles. We aimed to develop and validate a screening method by means of enzyme-linked immunosorbent assay (ELISA) for detection of kratom habitual users. An ELISA approach was applied for the development of a screening method using urinary AZ122 as biomarker. Method validation was carried out using three quality control materials at different concentration of AZ122. The data was analyzed statistically using SPSS (Version 25). The ELISA was presented with Pearson correlation coefficient of 0.9993. The repeatability and reproducibility were presented at CV <7%, while the accuracy ranged from 78 to 96% at various AZ112 concentrations. Upon testing on 176 male respondents (n = 88 regular kratom users and n = 88 healthy controls), the specificity and sensitivity of the assay were both 100%. The ELISA has been validated and can be potentially used as a reliable screening test for detection of kratom habitual users.
    Matched MeSH terms: Mitragyna*
  10. Singh D, Narayanan S, Vicknasingam B, Prozialeck WC, Smith KE, Corazza O, et al.
    J Addict Med, 2021 5 19;16(2):223-228.
    PMID: 34001777 DOI: 10.1097/ADM.0000000000000876
    OBJECTIVES: Kratom (Mitragyna speciosa Korth.), an indigenous medicinal plant, has been widely used as a traditional remedy in Southeast Asia. However, its combined consumption with other substances has received scarce attention. This study investigates the use of kratom among adults with a history of using heroin and methamphetamine in Malaysia.

    METHODS: A total of 332 patients who were mandated to undergo drug rehabilitation participated in this cross-sectional study. The study data were collected through face-to-face interviews using a semi-structured questionnaire.

    RESULTS: The majority were males (95%, n = 314/332) and Malays (98%, n = 325/332) with a mean age of 32.3 years (SD = 9.16). Over two thirds of the respondents used kratom to alleviate heroin withdrawal symptoms and to reduce methamphetamine intake; 59% used it as a substitute for heroin and methamphetamine. A similar proportion used kratom to reduce heroin intake (58%), while only 15% used it for its euphoric effects. Multivariate analysis showed that previous attendees of government rehabilitation programs had lower odds of using kratom as a heroin substitute.

    CONCLUSIONS: The potential of kratom to alleviate heroin withdrawal symptoms, and to reduce methamphetamine and heroin intake, among people who co-use heroin and methamphetamine warrants further research.

    Matched MeSH terms: Mitragyna*
  11. Coonan E, Tatum W
    Epilepsy Behav, 2021 04;117:107882.
    PMID: 33690067 DOI: 10.1016/j.yebeh.2021.107882
    Illicit drugs are used to produce a sense of euphoria in the user. Like marijuana, kratom is a plant-based substance. The leaves of the Mitragyna speciosa tree were used to treat mild medical conditions in Thailand and Malaysia as a stimulant in low doses, and sedative and analgesic at high doses. Over recent years, kratom gained popularity as a recreational drug among younger individuals in Southeast Asia due to its availability as a cheap and easily assessable substance with euphoric effects. This trend has rapidly made its way to the West. Unlike marijuana, in the United States kratom's use as an inexpensive herbal recreational "supplement" is poorly popularized. However, emerging reports garnished from use as a recreational drug reveals a potential health hazard. Seizures and neurological consequences have been reported from kratom abuse. Complex pharmacokinetics place patients at further risk of side effects and drug interactions. Still, individuals can legally purchase kratom at stores and through online distributers in capsule form or as teas, powders, and extracts under the veil of a harmless herbal remedy. Without United States Food and Drug Administration oversight, kratom has a high potential for abuse and without regulatory control threatens public safety.
    Matched MeSH terms: Mitragyna*
  12. Grundmann O, Babin JK, Henningfield JE, Garcia-Romeu A, Kruegel AC, Prozialeck WC, et al.
    Addiction, 2021 01;116(1):202-203.
    PMID: 32602213 DOI: 10.1111/add.15173
    Matched MeSH terms: Mitragyna*
  13. Fauzi NAM, Tan ML, Hamid SBS, Singh D, Abdullah MFILB
    J Addict Med, 2022 2 28;16(6):e374-e381.
    PMID: 35220333 DOI: 10.1097/ADM.0000000000000988
    OBJECTIVES: This study determined the association between expression of the endoplasmic reticulum (ER) stress sensor mRNA in the peripheral leukocytes and the patterns of kratom use and evaluated the correlations between the levels of the ER stress sensor mRNA and the severity of kratom dependence and kratom induced depressive symptoms among people who use kratom (PWUK).

    METHODS: A total of 20 PWUK and 20 age matched non-kratom using healthy controls were recruited. Data collected from PWUK included patterns of kratom use, severity of kratom dependence, and severity of depressive symptoms during abstinence from kratom. The mRNA expression of binding immunoglobulin protein ( BiP ), X-box binding protein 1, activating transcription factor 4, and C/-EBP homologous protein ( CHOP ) (major indicators of ER stress response) were analyzed using quantitative reverse transcription polymerase chain reaction in leucocyte-derived total RNA sample of the participants.

    RESULTS: PWUK regardless of their pattern of kratom use recorded significantly higher expression of BiP mRNA compared with controls. Expression of CHOP mRNA was only significantly higher in those who first consumed kratom at the age of 18 years and above and those who have been using kratom for longer than 6 years, compared with controls. Higher expression of BiP , ATF4 , and CHOP mRNA were significantly positive correlated with greater severity of kratom dependence. Although only higher expression of BiP and CHOP mRNA were significantly positively correlated with greater severity of depressive symptoms.

    CONCLUSIONS: Regular kratom consumption may activate the ER stress pathway and there may be a link between altered ER stress response and kratom dependence and kratom induced depressive symptoms.

    Matched MeSH terms: Mitragyna*
  14. Grundmann O, Veltri CA, Morcos D, Knightes D, Smith KE, Singh D, et al.
    Am J Drug Alcohol Abuse, 2022 Jul 04;48(4):433-444.
    PMID: 35389321 DOI: 10.1080/00952990.2022.2041026
    Background: Kratom (Mitragyna speciosa Korth.) use outside of Southeast Asia has increased over the past decade. Objectives: This investigation clarifies kratom's role in perceived well-being, overall health, and temporal correlation with drug use to understand kratom's role in the self-treatment of substance use disorders (SUDs). Methods: Between July 2019 and July 2020 an anonymous, cross-sectional, online survey was taken by 7,381 people who use kratom (PWUK) recruited through social media and other online resources. This included an assessment of (a) the relationship between self-reported overall health, concomitant use of drugs of misuse, and demographics; (b) the perceived effectiveness of kratom in self-treating diagnosed health conditions or symptoms; (c) the profile of PWUK primarily for drug dependence, pain, and mood or mental health conditions based on demographics. Results: A total of 5,152 valid responses (45.9% females/53.7% males) were collected. Kratom was primarily used for self-treating pain (73.0%) and improving emotional or mental health conditions (42.2%) without clinical supervision. Those with a SUD (synthetic opioids, methadone, benzodiazepines, or heroin) used kratom after discontinuing illicit or other drugs (94.8%). The primary substances taken before or concomitantly with kratom were cannabis, cannabidiol, benzodiazepines, or kava. PWUKs report a dose-dependent benefit for alleviating pain and relieving negative moods. Adverse effects were primarily gastrointestinal, typically at high (>5 g/dose) and frequent (>22 doses/week) dosing. Conclusions: Kratom was primarily used as a harm-reduction agent for SUDs and self-treatment of chronic conditions. Healthcare professionals need better information about kratom, its potential adverse effects, and clinically significant drug interactions.
    Matched MeSH terms: Mitragyna*
  15. Khalid K, Ku Md Saad S, Soelar SA, Mohamed Yusof Z, Warijo O
    J Ethn Subst Abuse, 2023;22(1):121-132.
    PMID: 33784945 DOI: 10.1080/15332640.2021.1906816
    Kratom is a plant homogenous to Southeast Asia with a long history of traditional use as medicinal herbs. However, recent years have witnessed its pervasive infiltration into international audience with growing public health concern. This cross-sectional study was conducted from 1 August 2017 till 31 August 2018 aiming to explore the practice and perspectives of kratom use and misuse among adolescents in northwest Malaysia. The study involved a self-administered questionnaire that was designed for the purpose of the study. The instrument had undergone prior validation process with a good overall internal reliability for the knowledge domain (Cronbach's alpha = 0.728) and attitude domain (Cronbach's alpha = 0.700). The questionnaire was distributed to 135 respondents involving adolescents aged 13 to 19 years old via convenience (non-kratom user) and snowball sampling (kratom users). There were 65 (47.8%) kratom users, while 70 (51.5%) were kratom-naïve. Among the kratom users, peer influence was the most common reason for them to be first involved with kratom, 26 (41.3%) whereas the reasons for kratom use quoted were to improve physical stamina, 10 (16.4%), as painkiller, 9 (14.8%), and to be accepted by peers, 7 (11.5%). Multiple logistic regression found that older age (95% CI: 0.13, 0.58; p = 0.001) and being active smokers (95% CI: 39.33, 980.63; p 
    Matched MeSH terms: Mitragyna*
  16. Grundmann O, Veltri CA, Morcos S, Smith KE, Singh D, Corazza O, et al.
    Exp Clin Psychopharmacol, 2023 Oct;31(5):963-977.
    PMID: 36634016 DOI: 10.1037/pha0000632
    Kratom (Mitragyna speciosa Korth.) use has increased substantially over the past decade outside of its indigenous regions, especially for the self-treatment of psychiatric conditions. An anonymous, cross-sectional, online survey was completed by 4,945 people who use kratom (PWUK) between July 2019 and July 2020. A total of 2,296 respondents completed an extended survey that included clinical scales for measuring attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), depressive and anxiety disorders. PWUK and met criteria for ADHD, PTSD, depressive or anxiety disorders were primarily middle-aged (31-50 years), employed, college-level educated, and reported greater concurrent or prior use of kratom with cannabis, cannabidiol, and benzodiazepines. For all psychiatric conditions, PWUK reported decreased depressive and anxious moods than before kratom use. Based on this self-report study, observational and other clinical studies are warranted for kratom. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
    Matched MeSH terms: Mitragyna*
  17. You CY, Hassan Z, Müller CP, Suhaimi FW
    Psychopharmacology (Berl), 2022 Jan;239(1):313-325.
    PMID: 34693456 DOI: 10.1007/s00213-021-05996-4
    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.

    Matched MeSH terms: Mitragyna*
  18. Yang B, Tan ML, Zhang R, Singh D, Leong Bin Abdullah MFI
    PLoS One, 2023;18(6):e0287466.
    PMID: 37352311 DOI: 10.1371/journal.pone.0287466
    BACKGROUND AND AIMS: Kratom (Mitragyna speciosa Korth.) is widely use worldwide despite its addictive potential. Although psychostimulant use has been linked to occurrence of endoplasmic reticulum (ER) stress, data is lacking on how regular kratom use affects ER stress. This case-control study first determined differences in ER stress sensor protein expression (BiP, sXBP1, ATF4, CHOP, JNK, and p-JNK) between regular kratom users and healthy controls. Second, it evaluated the association between kratom use characteristics, targeted ER stress sensor protein expression, and "kratom use disorder" diagnosed with Diagnostic and Statistical Manual for Mental Disorders 5th Edition (DSM-5) among regular kratom users.

    METHODS: In total, 60 regular kratom users and 50 healthy control-group participants were recruited and administered a sociodemographic and clinical characteristics questionnaire. While participants who used kratom were also administered a kratom use characteristics questionnaire. Blood samples were collected from all participants, and targeted ER stress sensor protein expression was determined via Western blot analysis.

    RESULTS: The study's findings revealed first that kratom users registered significantly higher protein expression in all targeted ER stress sensors compared to the control group. Second, higher protein expression of CHOP (B = 5.061, standard error [SE] = 2.547, Wald = 3.948, adjusted odds ratio [AOR] = 5.382, 95% confidence interval [CI] = 1.071 to 9.656, p = 0.047) and p-JNK (B = 5.795, SE = 2.635, Wald = 4.544, AOR = 17.025, 95% CI = 1.395 to 24.123, p = 0.017) increased the odds of kratom use disorder occurrence. Kratom use characteristics and other ER stress sensor protein expression were not associated with kratom use disorder.

    CONCLUSION: Regular kratom use may induce protracted ER stress, leading to the decompensation of the unfolded protein response to maintain ER homeostasis. This effect may be linked to kratom use disorder occurrence.

    Matched MeSH terms: Mitragyna*
  19. Japarin RA, Harun N, Hassan Z, Shoaib M
    Behav Pharmacol, 2023 Apr 01;34(2-3):123-130.
    PMID: 36752325 DOI: 10.1097/FBP.0000000000000715
    Mitragynine (MG) is a pharmacologically active alkaloid derived from the leaves of Mitragyna speciosa Korth (Kratom). This plant has sparked significant interest as a potential alternative treatment for managing opioid dependence and withdrawal due to its opioid-like pharmacological effects. However, whether MG exposure would trigger opioid-seeking behaviour following abstinence has not been investigated. The present study examined the effects of MG priming on morphine-seeking behaviour in rats. Male Sprague-Dawley rats were initially trained to intravenously self-administer morphine (0.5 mg/kg/infusion) under a fixed ratio-3 schedule of reinforcement. Removal of both morphine infusions and drug-associated cues led to the subsequent extinction of the drug-seeking behaviour. Tests of reinstatement were made following exposure to a randomised order of intraperitoneal injections of MG (3, 10 and 30 mg/kg), morphine (5 mg/kg) and vehicle. Significant levels of drug-seeking behaviour were observed following extended access to morphine self-administration, which was extinguished following removal of morphine and cues indicative of morphine-seeking behaviour, supporting the relapse model. The present finding demonstrated that MG priming in a dose of 10 mg/kg resulted in the reinstatement of morphine-seeking behaviour, whereas the higher MG dose (30 mg/kg) tested suppressed the seeking response. This study indicated that exposure to a low MG dose may increase the likelihood of relapsing to opioids, suggesting that the potential of MG as a treatment for opioid management merits further scientific assessment of its ability to trigger relapse to opioid abuse.
    Matched MeSH terms: Mitragyna*
  20. Ghazalli MN, Md Sah MS, Mat M, Awang K, Jaafar MA, Mirad R, et al.
    Trop Life Sci Res, 2021 Mar;32(1):107-117.
    PMID: 33936554 DOI: 10.21315/tlsr2021.32.1.7
    Mitragyna speciosa (Korth.) Havil. or locally known as ketum/daun sebiak/biak-biak belongs to Rubiaceae family and generally occurs in secondary forest or disturbed areas in tropical and subtropical region. This research enumerated the characterisation of Mitragyna speciosa leaf anatomy and micromorphology features which is still not well documented. This medium to large sized tree species characterised with opposite arrangement, ovate-acuminate leaf and with 12-17 pairs of veins. Transverse sections of petioles showed that this species has petiole outlines with slightly convex at the middle of the adaxial part and 'U'-shaped on abaxial side. Results also showed that this species has paracytic and hypostomatic stomata, combination of non-glandular (majority) and glandular trichomes (minority), with observation on the secretory cells present in petiole and midrib parenchyma cells. Cuticle on the abaxial and adaxial epidermal surfaces showed the presence granule and wax films with periclinal and anticlinal walls can be differentiated clearly. The results obtained in this study can be used to providing additional systematics information of Mitragyna speciosa with the documentation of the leaf anatomy and micromorphology characters.
    Matched MeSH terms: Mitragyna
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