Kratom (Mitragyna speciosa) use in a sample of drug-dependent adolescents in rehabilitation for drug use in Malaysia.

BACKGROUND: Leaves derived from the Kratom (Mitragyna speciosa) tree have been traditionally ingested for their curative properties by diverse groups of the population including people who use drugs (PWUDs) in Southeast Asia. This study investigated the motives for using kratom among drug-dependent adolescents. METHODS: Eighty adolescents who were undergoing mandatory drug rehabilitation volunteered to participate in this mixed-method, cross-sectional study. All respondents answered a semi-structured questionnaire while a few were interviewed in-depth. RESULTS: The majority were males (70%, n = 56/80). The respondents' mean age at admission was 18.2 years (SD = 1.40), and 65% were between 14 and 18 years old. Sixty-three percent (n = 50/80) had used crystal methamphetamine alone, while the rest had co-used crystal methamphetamine with heroin. About three-fifths (60%, n = 48/80) had a history of kratom use. Kratom was commonly used for many perceived benefits such as increasing energy, reducing crystal methamphetamine intake, intensifying euphoria, easing heroin withdrawal, as a heroin substitute and reducing heroin use. In addition, the multivariate analysis indicated that higher odds of kratom use were associated with those who were employed, used only crystal methamphetamine, were recent drug users, and had no prior incarceration history. CONCLUSION: While kratom was being used for its multifold perceived benefits, it also functions as a means to self-treat withdrawal from illicit drug use among drug-dependent adolescents.

Advancing Healthcare: Synergizing Biosensors and Machine Learning for Early Cancer Diagnosis.

Cancer is a fatal disease and a significant cause of millions of deaths. Traditional methods for cancer detection often have limitations in identifying the disease in its early stages, and they can be expensive and time-consuming. Since cancer typically lacks symptoms and is often only detected at advanced stages, it is crucial to use affordable technologies that can provide quick results at the point of care for early diagnosis. Biosensors that target specific biomarkers associated with different types of cancer offer an alternative diagnostic approach at the point of care. Recent advancements in manufacturing and design technologies have enabled the miniaturization and cost reduction of point-of-care devices, making them practical for diagnosing various cancer diseases. Furthermore, machine learning (ML) algorithms have been employed to analyze sensor data and extract valuable information through the use of statistical techniques. In this review paper, we provide details on how various machine learning algorithms contribute to the ongoing development of advanced data processing techniques for biosensors, which are continually emerging. We also provide information on the various technologies used in point-of-care cancer diagnostic biosensors, along with a comparison of the performance of different ML algorithms and sensing modalities in terms of classification accuracy.

Temporal variability, meteorological influences, and long-range transport of atmospheric aerosols over two contrasting environments Agartala and Patiala in India.

The present study focused on the temporal variability, meteorological influences, potential sources, and long-range transport of atmospheric aerosols over two contrasting environments during 2011-2013. We have chosen Agartala (AGR) city in Northeast India as one of our sites representing the rural-continental environment and Patiala (PTA) as an urban site in Northwest India. The seasonal averaged equivalent black carbon (eBC) concentration in AGR ranges from 1.55 to 38.11 µg/m3 with an average value of 9.87 ± 8.17 µg/m3, whereas, at an urban location, PTA value ranges from 1.30 to 15.57 µg/m3 with an average value of 7.83 ± 3.51 µg/m3. The annual average eBC concentration over AGR was observed to be ~ 3 times higher than PTA. Two diurnal peaks (morning and evening) in eBC have been observed at both sites but were observed to be more prominent at AGR than at PTA. Spectral aerosol optical depth (AOD) has been observed to be in the range from 0.33 ± 0.09 (post-monsoon) to 0.85 ± 0.22 (winter) at AGR and 0.47 ± 0.04 (pre-monsoon) to 0.74 ± 0.09 (post-monsoon) at PTA. The concentration of eBC and its diurnal and seasonal variation indicates the primary sources of eBC as local sources, synoptic meteorology, planetary boundary layer (PBL) dynamics, and distant transportation of aerosols. The wintertime higher values of eBC at AGR than at PTA are linked with the transportation of eBC from the Indo-Gangetic Plain (IGP). Furthermore, it is evident that eBC aerosols are transported from local and regional sources, which is supported by concentration-weighted trajectory (CWT) analysis results.

A Preliminary Inventory of Kratom (Mitragyna Speciosa) Products and Vendors on the Darknet and Cryptomarkets.

In recent years, the online sale of kratom (Mitragyna speciosa), a Southeast Asian plant with both medicinal and psychoactive properties, has raised health concerns mainly due to the uncontrolled diffusion of adulterated kratom-related products. This exploratory study provides, for the first time, a snapshot of the availability of kratom products on the darknet which has been further validated by data searches on the surface web. A total of 231 listings of kratom across 23 darknet marketplaces were identified between March 2020 and October 2021. Among these, 40 were found actively sold across five markets by thirteen vendors. Listed items were mainly advertised as "safe" substitutes for medicinal products for the self-management of pain and other health conditions and offered in various forms (e.g., dry leaf powder, pills, capsules). Purchases were made using cryptocurrencies, with some vendors offering Pretty Good Privacy, and were shipped from Europe, Australia, the United States, and the United Kingdom. Goods sold by the same sellers also included illicit drugs and fraud-related products. Our study discovered a previously unknown diffusion of kratom products on the darknet mainly for self-treating a variety of medical conditions, suggesting the need for further research and immediate interventions to safeguard the well-being and health of kratom consumers.

Evaluation of toxicity profile of kratom (Mitragyna speciosa Korth) decoction in rats.

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.

The Health Impact of Long-Term Kratom (Mitragyna Speciosa) Use in Southern Thailand.

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.

Kratom use disorder and unfolded protein response: Evaluating their relationship in a case control study.

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.

Formation and characterization of leaf waste into organic compost.

In solid waste management, pollution-free disposal of leaf waste in urban areas is still not standardized and adopted. According to the World Bank report, 57% of wastes generated in South East Asia are consisted of food and green waste, which can be recycled into valuable bio-compost. The present study shows a method of leaf litter waste management by composting it using essential microbe (EM) method. Different parameters, such as pH, electrical conductivity, macronutrients, micronutrients, and potentially toxic elements (PTE) were measured at zero to 50 days of composting using appropriate methods. The microbial composting was shown to mature within 20 to 40 days, and its maturity could be evaluated by the attainment of stable pH (8), electrical conductivity (0.9 mS/cm), and C:N ratio ≥ 20. The analysis was also performed on other bio-composts viz. kitchen waste compost, vermicompost, cow dung manure, municipal organic waste compost, and neem cake compost. The fertility index (FI) was evaluated based on six parameters viz. total carbon, total nitrogen, N ratio, phosphorus, potassium, and sulphur contents. The PTE values were used to calculate their clean index (CI). The results showed that leaf waste compost has a higher fertility index (FI = 4.06) than other bio-composts, except the neem cake compost (FI = 4.44). The clean index of the leaf waste compost (CI = 4.38) was also higher than other bio-composts. This indicates that leaf waste compost is a valuable bio-resource with high nutritive value and low PTE contamination, with a favourable prospective to be used in organic farming.

Deconstructing Differential Drug Coverage within a Malaysian Media Source.

Many researchers have noted that media coverage of drugs can be sensationalized and/or have questionable accuracy. Additionally, it has been alleged that the media often treats all drugs as harmful and can fail to differentiate between different types of drugs. Within this context, the researchers sought to deconstruct how media coverage was similar and/or different according to drug type within a national media outlet in Malaysia. Our sample comprised 487 news articles published over a two-year period. Articles were coded to reflect thematic differences in drug framing. We focus on five drugs widely used in Malaysia (amphetamines, opiates, cannabis, cocaine, and kratom) and assess the most frequent themes, crimes, and locations mentioned in reference to each drug. All drugs were primarily covered in a criminal justice context, and articles highlighted concern about the spread of these drugs and their abuse. Drug coverage varied, particularly in association with violent crimes, specific regions, and discussion of legality. We find evidence of both similarities and differences in how drugs were covered. Variation in coverage demonstrated that certain drugs were deemed a heightened threat, as well as reflected broader social/political processes shaping ongoing debates over treatment approaches and legality.

Correlations of kratom (Mitragyna speciosa Korth.) use behavior and psychiatric conditions from a cross-sectional survey.

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).

Factors associated with drug use during pregnancy and breastfeeding among females who use drugs (FWUDs) in Malaysia.

Females who use drugs (FWUDs) are at risk of continuing illicit substance use during pregnancy and breastfeeding. We investigated the prevalence rates and factors associated with these practices in a sample of 200 FWUDs recruited from a publicly-run drug rehabilitation center. A semi-structured questionnaire was used to collect the data. The majority (86%) was Malay (n = 171/200), currently single (71%, n = 141/200), and 51% had nine years of education. The mean age of respondents was 32.2 years (SD = 8.61). Thirty-eight percent (n = 75/200) reported ever using illicit substances during pregnancy, while 15% (n = 30/200) had used them during breastfeeding. Higher odds of using drugs during pregnancy were associated with having an intimate male drug-using partner and with persons who reported abandoning an infant in the past. Lower odds were linked with women who used heroin with ATS (relative to those who used only ATS), and shorter-term ATS (≤3 years) relative to long term ATS users. At a lower level of significance (p = 0.054), being married also lowered the odds. Higher odds of drug use during breastfeeding were associated with having an intimate male drug-using partner, and previous methadone use history, while lower odds were associated with short-term ATS use and being employed. The findings highlight the need for timely and targeted interventions to inform, engage and promote the participation of FWUDs in pre- and post-natal care services.

Development and validation of ELISA for screening of Kratom (Mitragyna speciosa) habitual users using urinary AZ122 biomarker.

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.

Barriers to enrolling in voluntary treatment programs in Malaysia: a study of women who use methamphetamine (WWUM).

Women with substance use disorders (SUDs) have been widely reported to face barriers in seeking treatment. We sought to identify barriers that prevented women who use methamphetamine (WWUM) from accessing the decade-old Voluntary Treatment Centers (VTCs) in Malaysia. A total of 153 WWUM who were undergoing rehabilitation for methamphetamine use at a compulsory drug detention center (CDDC) were recruited for this cross-sectional study. Data were collected by canvasing a structured questionnaire through face-to-face meetings. Of the total sample, 131 (86%) were Malays, with a mean age of 32.1 years. The commonly cited treatment barriers were the belief that methamphetamine use was not problematic (42%), not knowing how to seek treatment (38%), feeling embarrassed to seek treatment (33%), the lack of family support (24%), and the long waiting time for enrollment (23%). Logistic analyses indicated that a longer duration of use increased the odds of not acknowledging methamphetamine use as a problem while older participants had lower odds of holding a similar view. A longer duration of use also increased the odds of claiming treatment was not needed but lowered the odds of asserting a lack of confidence in treatment. Furthermore, Malays had higher odds of lacking family support in seeking treatment while being employed lowered the odds of not wanting treatment. Addressing these concerns will hopefully encourage higher participation of WWUM in voluntary treatment programs.

Need for clarity and context in case reports on kratom use, assessment, and intervention.

This Letter to the Editor is a response to Broyan and colleagues who recently published a Case Report presenting data on 28 patients in the United States who identified kratom as their primary substance of use and who were subsequently induced on buprenorphine/naloxone for a reported diagnosis of kratom use disorder. We applaud the authors for helping to advance the science on kratom and recognize the difficulties in conducting kratom-related clinical assessment and research. However, a number of inconsistences and generalizations were identified in this Case Report, which also lacked some critical context. Importantly, such inconsistencies and generalizations can be observed throughout kratom-specific case reports. We feel this is now an important opportunity to highlight these issues that are present in the Broyan and colleagues Case report but emphasize that they are not unique to it. We do this with the hope that by acknowledging these issues it can help inform editors, clinicians, and researchers who may not be familiar with kratom and, as a result of this unfamiliarity, may inadvertently present findings in a manner that could confuse readers and even misinform clinical researchers and practitioners.

Exploring the self-reported motivations of kratom (Mitragyna speciosa Korth.) use: a cross-sectional investigation.

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.

Regular Kratom ( Mitragyna speciosa Korth.) Use and Its Association With Endoplasmic Reticulum Stress Response.

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.

Client satisfaction to methadone maintenance treatment program in Myanmar.

BACKGROUND: To tackle the long-standing opioid misuse problem, Myanmar introduced the methadone maintenance treatment (MMT) program in 2006, starting with 260 clients. Since then, the program has been expanded across different geographical sites in the country. This study was done in 2017 to explore the treatment satisfaction of the clients towards the MMT program. METHOD: A total of 210 clients with a minimum of six-month treatment history enrolled in five MMT program sites across Myanmar were recruited through stratified random sampling. Administering the Verona Service Satisfaction Scale for Methadone-Treatment (VSSS-MT), this study assessed the satisfactory responses under three categories viz., 1) clinic staff professional skills; 2) basic drug intervention; 3) specific intervention (individual rehabilitation and psychotherapy). RESULTS: The majority (89%, n = 186) of the respondents were satisfied with the current MMT program. Specifically, 89.5% (n = 187) were satisfied with the clinic staff professional skills category, 91.9% (n = 192) with the basic program intervention and 74.6% (n = 156) with specific interventions. Among the respondents, treatment satisfaction with the MMT program was higher (p < 0.05) in those (i) with a higher quality of life score in physical, psychological, social and environmental categories, ii) who were satisfied with their current marital and leisure status, and those iii) who consumed alcohol. Results from stepwise binary logistic regression showed alcohol consumption and physical health status had a significant association with MMT treatment satisfaction. CONCLUSION: Treatment satisfaction of the clients, in general is high. However, the lower percentage of satisfied clients (74.6%) for the specific interventions category compared with 89.5 and 91.9% respectively for staff and basic drug management categories highlights the need for improvement in this category for overall enhancement of the MMT program.