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  1. Bin Abdullah MFIL
    Curr Drug Targets, 2020;21(15):1566-1579.
    PMID: 32682371 DOI: 10.2174/1389450121666200719011653
    Kratom, or Mitragyna speciosa Korth., is a tropical plant prevalent in Southeast Asia, and it is utilized as a traditional remedy for symptomatic relief of various illnesses. It has been labeled as an atypical opioid with significant narcotic-like properties, capable of inducing kratom dependence among those who misuse or abuse it. The prevalence of kratom use has drastically increased worldwide, raising concerns among healthcare providers, particularly regarding the availability of efficacious treatment options for kratom dependence. This manuscript provides a comprehensive narrative review of literature focusing on the psychoactive alkaloids of kratom, the possible neurobiological and pathophysiological models underlying the occurrence of kratom dependence, and the clinical presentations and effective treatment options available for kratom dependence. The psychoactive alkaloids of kratom, such as mitragynine (MG) and 7-hydroxymitragynine (7-HMG), act as partial mu opioid agonists and induce kratom dependence. As a result, regular kratom use leads to withdrawal symptoms on abstinence, along with craving, tolerance, and cross-tolerance to morphine. The psychological withdrawal symptoms reported include depressed mood, anxiety, restlessness, irritability, and feeling tense, while the physical withdrawal symptoms are myalgia and body ache, joint pain, lacrimation, running nose, yawning, insomnia, diarrhea, feverish sensation, loss of appetite, tremors, itching over the body, loss of concentration, and chills. Neonatal withdrawal symptoms, such as oral intolerance, restlessness, irritability, and vomiting, are also reported in newborns of women who are on regular kratom use. Sublingual buprenorphine-naloxone (Suboxone) is reported as a promising treatment for detoxification and maintenance replacement therapy for kratom-dependent users. Alternative treatments for in-patient detoxification include intravenous clonidine and a combination of oral dihydrocodeine and lofexidine. We conclude by adding a note on the research gap concerning kratom dependence, which future studies should focus on.
  2. Azman N, Thien LM, Abdullah MFIL, Mohd Shariff N
    PMID: 34501991 DOI: 10.3390/ijerph18179403
    (1) Background: This study aimed to assess the psychometric properties of the Malay version of SCNS-SF34 among Malaysian cancer patients. (2) Methods: This cross-sectional study involved 171 cancer patients. Data were collected using the structured five-factor survey via telephone call or face-to-face interviews. The internal reliability and the construct validity of SCNS-34M were analysed using principal component analysis with varimax rotation. (3) Results: The health system and information need (HSI) was the domain with the highest mean score (2.73 ± 0.88), followed by patient care and support needs (2.16 ± 0.90), as well as physical and daily living needs (1.99 ± 0.98). The confirmatory factor analysis indicated a moderate model fit for RMSEA with 0.070, TLI = 0.911 and CFI = 0.924. (4) Conclusions: The SCNS-SF34M was found to be a conceptually applicable and culturally appropriate scale in measuring the supportive care for cancer patients within the Malaysian context.
  3. Singh D, Narayanan S, Abdullah MFIL, Vicknasingam B
    J Ethn Subst Abuse, 2020 Nov 16.
    PMID: 33190622 DOI: 10.1080/15332640.2020.1845899
    Out-of-treatment HIV positive opiate users often engage in risky injecting and sexual behaviors. We sought the self-reported experiences on whether or not kratom (Mitragyna speciosa Korth.) use was associated with a reduction in HIV risk behaviors among them. A convenience sample consisting of thirty-two HIV positive opiate users participated in the study. Of this, three-fifths (n = 20/32) used kratom to suppress opiate withdrawal, increase energy, as a heroin substitute, to reduce heroin dependence and self-treat psychological problems. More than one-third (38%) in the sample claimed that kratom use reduced their risky injecting and sexual behaviors. Given the small sample size, the perceived association between kratom use and the reduction in HIV risk behaviors could not be established more convincingly. However, the findings provide the basis for a broader-based study to evaluate the potential of kratom in curtailing HIV risk behaviors among HIV positive opiate users.
  4. Yu J, Abdullah MFIL, Mansor NS
    Brain Behav, 2024 Jan;14(1):e3388.
    PMID: 38376031 DOI: 10.1002/brb3.3388
    BACKGROUND: Inhibitory control ability is a crucial cognitive function that enables individuals to regulate their impulses and behaviors in a goal-directed manner. However, with the increasing prevalence of internet gaming disorder (IGD), there has been growing concern about the impact of excessive gaming on inhibitory control ability. Despite the accumulating evidence on this topic, the research conclusion on whether people with IGD have worse inhibition control ability than healthy controls remains inconsistent, and the lack of effective electroencephalography prediction indicators further complicates this issue. To address this research gap, the present study aimed to investigate whether N2 event-related potential (ERP) and P3 ERP components could serve as reliable indicators of inhibitory control ability in individuals with IGD.

    METHODS: To achieve this goal, a systematic literature search was conducted in several databases, including Web of Science, ScienceDirect (EBSCO), SpringerLink, PubMed, and Wiley Online Library. The inclusion criteria were strictly implemented to ensure the quality of the studies included in the meta-analysis. In the end, a total of 5 studies, with 139 participants diagnosed with IGD and 139 healthy controls, were included in the analysis.

    RESULTS: Meta-analysis revealed large effect sizes of N2 and P3 amplitudes in individuals with IGD, indicating that these two ERP components could be potential indicators of inhibitory control ability. Specifically, the N2 and P3 amplitude was significantly larger in individuals with IGD than in the healthy control group, suggesting deficits in inhibitory control function and increased impulsivity in the IGD group. In the inhibition control task, the IGD group required more cognitive resources to suppress impulsive responses.

    CONCLUSION: Overall, the findings of this meta-analysis shed light on the potential use of N2 and P3 amplitudes as reliable indicators of inhibitory control ability in individuals with IGD. The results provide crucial insights into the neural mechanisms underlying inhibitory control impairment in IGD, which could inform the development of effective interventions for this condition. Further research is needed to explore the functional significance of these ERP components and their potential clinical applications in the diagnosis and treatment of IGD.

  5. Abduraman MA, Amanah A, Hamid SBS, Abdullah MFIL, Sulaiman SF, Tan ML
    J Pharm Pharmacol, 2024 Nov 14.
    PMID: 39541262 DOI: 10.1093/jpp/rgae131
    OBJECTIVES: Kratom preparation containing Mitragyna speciosa Korth plant is frequently used as a recreational drug. Mitragynine, a major alkaloid isolated from M. speciosa, is often detected concurrently with other drugs during forensic analysis, indicating a safety concern. P-glycoprotein (P-gp) is a multidrug transporter. Modulation of P-gp transport activity by drugs or herbal compounds in the brain may lead to drug-herb interactions, resulting in neurotoxicity. We aim to determine the effects of mitragynine on the P-gp regulation and possible neurotoxicity.

    METHODS: The effects of mitragynine on the P-gp regulation were investigated in human brain capillary endothelial cells (hCMEC/D3) using molecular docking and dynamic simulation and an optimized bidirectional transport assay, respectively. Repeated-dose treatment and neurotoxicity assessment were carried out using a blood-brain barrier model and polimerase chain reaction (PCR) array.

    KEY FINDINGS: Mitragynine inhibits the P-gp transport activity via binding onto the nucleotide-binding domain site and forms a stable interaction with the P-gp protein complex. Nontoxic concentrations of mitragynine (<4 μM) and substrate drugs (0.001 μM) in the cells significantly enhanced endothelial cell permeability and elicited signs of neurotoxicity in PC-12 cells.

    CONCLUSIONS: Mitragynine is likely a P-gp inhibitor, hence concurrent administration of kratom products with P-gp substrates may lead to clinically significant interactions and neurotoxicity.

  6. Bahar Moni AS, Abdullah S, Bin Abdullah MFIL, Kabir MS, Alif SM, Sultana F, et al.
    PLoS One, 2021;16(9):e0257304.
    PMID: 34506576 DOI: 10.1371/journal.pone.0257304
    INTRODUCTION: The COVID-19 pandemic has enormously affected the psychological well-being, social and working life of millions of people across the world. This study aimed to investigate the psychological distress, fear and coping strategies as a result of the COVID-19 pandemic and its associated factors among Malaysian residents.

    METHODS: Participants were invited to an online cross-sectional survey from Aug-Sep 2020. The study assessed psychological distress using the Kessler Psychological Distress Scale, level of fear using the Fear of COVID-19 Scale, and coping strategies using the Brief Resilient Coping Scale. Univariate and multivariate logistic regression analyses were conducted to adjust for potential confounders.

    RESULTS: The mean age (±SD) of the participants (N = 720) was 31.7 (±11.5) years, and most of them were females (67.1%). Half of the participants had an income source, while 216 (30%) identified themselves as frontline health or essential service workers. People whose financial situation was impacted due to COVID-19 (AOR 2.16, 95% CIs 1.54-3.03), people who drank alcohol in the last four weeks (3.43, 1.45-8.10), people who were a patient (2.02, 1.39-2.93), and had higher levels of fear of COVID-19 (2.55, 1.70-3.80) were more likely to have higher levels of psychological distress. Participants who self-isolated due to exposure to COVID-19 (3.12, 1.04-9.32) and who had moderate to very high levels of psychological distress (2.56, 1.71-3.83) had higher levels of fear. Participants who provided care to a family member/patient with a suspected case of COVID-19 were more likely to be moderately to highly resilient compared to those who did not.

    CONCLUSION: Vulnerable groups of individuals such as patients and those impacted financially during COVID-19 should be supported for their mental wellbeing. Behavioural interventions should be targeted to reduce the impact of alcohol drinking during such crisis period.

  7. Chong HX, Yusoff NAA, Hor YY, Lew LC, Jaafar MH, Choi SB, et al.
    Benef Microbes, 2019 Apr 19;10(4):355-373.
    PMID: 30882244 DOI: 10.3920/BM2018.0135
    Probiotics have been reported to exert beneficial effects along the gut-brain axis. This randomised, double-blind and placebo-controlled human study aimed to evaluate such properties of Lactobacillus plantarum DR7 and its accompanying mechanisms in stressed adults. One hundred and eleven (n=111; DR7 n=56, placebo n=55) stressed adults were recruited based on moderate stress levels using the PSS-10 questionnaire. The consumption of DR7 (1×109 cfu/day) for 12 weeks reduced symptoms of stress (P=0.024), anxiety (P=0.001), and total psychological scores (P=0.022) as early as 8 weeks among stressed adults compared to the placebo group as assessed by the DASS-42 questionnaire. Plasma cortisol level was reduced among DR7 subjects as compared to the placebo, accompanied by reduced plasma pro-inflammatory cytokines, such as interferon-γ and transforming growth factor-α and increased plasma anti-inflammatory cytokines, such as interleukin 10 (P<0.05). DR7 better improved cognitive and memory functions in normal adults (>30 years old), such as basic attention, emotional cognition, and associate learning (P<0.05), as compared to the placebo and young adults (<30 years old). The administration of DR7 enhanced the serotonin pathway, as observed by lowered expressions of plasma dopamine β-hydroxylase (DBH), tyrosine hydroxylase (TH), indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase accompanied by increased expressions of tryptophan hydroxylase-2 and 5-hydroxytryptamine receptor-6, while stabilising the dopamine pathway as observed via stabilised expressions of TH and DBH over 12 weeks as compared to the placebo (P<0.05). Our results indicated that DR7 fulfil the requirement of a probiotic strain as per recommendation of FAO/WHO and could be applicable as a natural strategy to improve psychological functions, cognitive health and memory in stressed adults.
  8. Lew LC, Hor YY, Yusoff NAA, Choi SB, Yusoff MSB, Roslan NS, et al.
    Clin Nutr, 2019 10;38(5):2053-2064.
    PMID: 30266270 DOI: 10.1016/j.clnu.2018.09.010
    BACKGROUND & AIMS: To investigate the effects of probiotic in alleviation of stress in stressed adults, along our focus to identify and justify strain specificity on selected health benefits with a precisely targeted population.

    METHODS: This 12-weeks randomized, double-blind and placebo-controlled study investigated the effects of a probiotic (Lactobacillus plantarum P8; 10 log CFU daily) on psychological, memory and cognition parameters in one hundred and three (P8 n = 52, placebo n = 51) stressed adults with mean age of 31.7 ± 11.1 years old. All subjects fulfilled the criteria of moderate stress upon diagnosis using the PSS-10 questionnaire.

    RESULTS: At the end of study, subjects on P8 showed reduced scores of stress (mean difference 2.94; 95% CI 0.08 to 5.73; P = 0.048), anxiety (mean difference 2.82; 95% CI 0.35 to 5.30; P = 0.031) and total score (mean difference 8.04; 95% CI 0.73 to 15.30; P = 0.041) as compared to placebo after 4-weeks, as assessed by the DASS-42 questionnaire. Although plasma cortisol levels were only marginally different between placebo and P8 (mean difference 3.28 ug/dl; 95% CI -7.09 to 0.52; P = 0.090), pro-inflammatory cytokines such as IFN-γ (mean difference 8.07 pg/ml; 95% CI -11.2 to -4.93; P 

  9. Chong HX, Yusoff NAA, Hor YY, Lew LC, Jaafar MH, Choi SB, et al.
    J Dairy Sci, 2019 Jun;102(6):4783-4797.
    PMID: 30954261 DOI: 10.3168/jds.2018-16103
    The aims of this study were to investigate the effects of Lactobacillus plantarum DR7 isolated from bovine milk against upper respiratory tract infections (URTI) and elucidate the possible mechanisms underlying immunomodulatory properties. The DR7 strain (9 log cfu/d) was administered for 12 wk in a randomized, double-blind, and placebo-controlled human study involving 109 adults (DR7, n = 56; placebo, n = 53). Subjects were assessed for health conditions monthly via questionnaires, and blood samples were evaluated for cytokine concentrations, peroxidation and oxidative stress, and gene expression in T cells and natural killer (NK) cells. The administration of DR7 reduced the duration of nasal symptoms (mean difference 5.09 d; 95% CI: 0.42-9.75) and the frequency of URTI (mean difference 0.32; 95% CI: 0.01-0.63) after 12 and 4 wk, respectively, compared with the placebo. The DR7 treatment suppressed plasma proinflammatory cytokines (IFN-γ, TNF-α) in middle-aged adults (30 to 60 yr old), while enhancing anti-inflammatory cytokines (IL-4, IL-10) in young adults (<30 yr old), accompanied by reduced plasma peroxidation and oxidative stress levels compared with the placebo. Young adults who received DR7 showed higher expression of plasma CD44 and CD117 by 4.50- and 2.22-fold, respectively, compared with the placebo. Meanwhile, middle-aged adults showed lower expression of plasma CD4 and CD8 by 11.26- and 1.80-fold, respectively, compared with the placebo, indicating less T-cell activation. In contrast, both young and middle-aged adults who received DR7 showed enhanced presence of nonresting and mature NK cells compared with those who received the placebo. We postulate that DR7 alleviated the symptoms of URTI by improving inflammatory parameters and enhancing immunomodulatory properties.
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