Phytochemical analysis of water and ethanol liquid extracts prepared using freshly harvested leaves of Mitragyna speciosa (Korth.).

Mitragyna speciosa, also known as kratom, has been reported to have a broad range of pharmacological properties. Freshly harvested leaves and their water extracts are consumed in Southeast Asia while preparations made from dried leaf material are consumed in Western countries. Our study evaluated the phytochemical composition of freshly harvested kratom leaves using LCMS/MS analysis of water and ethanol liquid extracts. Mitragynine and its congeners, including 7-hydroxymitragynine, speciocilliatine, speciogynine, paynantheine, as well as bioactive phenolics including chlorogenic acid, o-coumaric acid, quercitrin, and rutin were identified. However, 7-hydroxymitragynine was detected solely in the water-liquid extract. Currently, unknown compounds were also present in the chromatograms and mass spectra. The study results support that 7-hydroxymitragynine is a post-harvest oxidative derivative or metabolite of mitragynine. Further rigorous and comprehensive evaluations of the phytochemical composition of freshly harvested kratom leaves utilising advanced spectrometric methods are needed to establish the full spectrum of phytochemicals within the plant.

Research and publication gaps on kratom and kratom products: a scoping review of current literature.

PURPOSE OF REVIEW: Kratom plant, products derived from the plant, and plant phytochemicals are of great interest among researchers, clinicians, and consumers. However, there is a paucity of rigorously collected scientific data on their risk/safety profile and public health impact. This scoping review discusses original research articles published between 2022 and 2023. It focuses on identifying publication gaps on topics related to epidemiology, public health, and risk/safety profiles comparing evidence collected by researchers from Southeast Asia and the West. RECENT FINDINGS: Our review of the Scopus database identified a total of 55 publications, including clinical case reports and case series reports, surveys, studies enrolling human participants, and publications based on large-scale national surveys or large-scale national or international health system database records. SUMMARY: Overall, there is dearth of reliable data on key epidemiological factors, including the prevalence rates, and on objective and reliable indices of the risk/safety profiles. Rigorous and systematic studies including improved epidemiological surveillance, human laboratory, and controlled clinical studies are urgently needed to advance our understanding of public health consequences of consuming kratom and kratom-derived products and to improve our understanding of their risk/safety profile and additional analytical studies to better inform development of needed regulatory oversight.

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.

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.

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.

Material Security Scale as a Measurement of Poverty among Key Populations At-Risk for HIV/AIDS in Malaysia: An Implication for People Who Use Drugs and Transgender People during the COVID-19 Pandemic.

The HIV epidemic is fueled by poverty; yet, methods to measure poverty remain scarce among populations at risk for HIV infection and disease progression to AIDS in Malaysia. Between August and November 2020, using data from a cross-sectional study of people who use drugs, (PWUD), transgender people, sex workers and men who have sex with men, this study examined the reliability and validity of a material security scale as a measurement of poverty. Additionally, we assessed factors associated with material security scores. We performed confirmatory factor analysis (CFA) for 268 study participants included in the analysis. A revised nine-item three-factor structure of the material security scale demonstrated an excellent fit in CFA. The revised material security score displayed good reliability, with Cronbach's alpha of 0.843, 0.826 and 0.818 for housing, economic resources and basic needs factors, respectively. In a subsequent analysis, PWUD and transgender people were less likely to present good material security scores during the pandemic, compared to their counterparts. The revised nine-item scale is a useful tool to assess poverty among key populations at-risk for HIV/AIDS with the potential to be extrapolated in similar income settings.

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.

Treatment Barriers Associated with Amphetamine-Type Stimulant (ATS) Use in Malaysia.

People who use amphetamine-type stimulant (ATS) are known to face barriers in seeking treatment. We sought to identify these barriers and gender differences in barriers (if any) faced by them. A convenience sample of 386 respondents who use ATS was recruited from five formal drug rehabilitation centers for this cross-sectional study. The majority were male (83%), with 17% being female. The barriers most frequently cited by both men and women were: the perception that ATS use needed no treatment, fears of community discrimination, peer influence, and long waiting time to get into a treatment programme. One-third of the sample held that the mandated treatment programmes were ineffective, based on past experience. In terms of male-female differences, long waiting time discouraged significantly more women than men, whereas more men than women asserted that formal treatment programmes were ineffective. We also found no significant differences in barriers faced by ATS users and those using ATS with other illicit substances. Outreach initiatives to minimize the impact of treatment barriers, coupled with offering separate treatment protocols and facilities, will encourage people who use ATS to seek treatment voluntarily.

The Use of Kratom (Mitragyna speciosa Korth.) Among People Who Co-use Heroin and Methamphetamine in Malaysia.

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.

COVID-19 Impact on Healthcare and Supportive Services for People Who Use Drugs (PWUDs) in Malaysia.

Background: Restrictive orders and temporary programmatic or ad hoc changes within healthcare and other supportive systems that were implemented in response to the COVID-19 epidemic in Malaysia may have created hindrances to accessing healthcare and/or receiving other supportive services for people who use drugs (PWUDs). Design: A primarily qualitative study has been conducted to evaluate how service providers and recipients were adapting and coping during the initial periods of the COVID-19 response. Settings: The study engaged several healthcare and non-governmental organizations (NGOs) in the peninsular states of Penang, Kelantan, Selangor, and Melaka. Participants: Medical personnel of methadone maintenance treatment (MMT) programs (n = 2) and HIV clinics (n = 3), staff of NGO services (n = 4), and MMT patients (n = 9) were interviewed using a semi-structured format. Results: Interviewed participants reported significant organizational, programmatic, and treatment protocols related changes implemented within the healthcare and support services in addition to nationally imposed Movement Control Orders (MCOs). Changes aimed to reduce patient flow and concentration at the on-site services locations, including less frequent in-person visits, increased use of telemedicine resources, and greater reliance on telecommunication methods to maintain contacts with patients and clients; changes in medication dispensing protocols, including increased take-home doses and relaxed rules for obtaining them, or delivery of medications to patients' homes or locations near their homes were reported by the majority of study participants. No significant rates of COVID-19 infections among PWUDs, including among those with HIV have been reported at the study sites. Conclusions: Although the reported changes presented new challenges for both services providers and recipients and resulted in some degree of initial disruption, generally, all participants reported successful implementation and high levels of compliance with the newly introduced restrictions, regulations, and protocols, resulting in relatively low rates of treatment disruption or discontinuation at the study sites.

Effects of kratom (Mitragyna speciosa Korth.) in reducing risk-behaviors among a small sample of HIV positive opiate users in Malaysia.

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.

Kratom and Pain Tolerance: A Randomized, Placebo-Controlled, Double-Blind Study.

Background: Kratom has a long history of traditional medicine use in Southeast Asia. Consumption of kratom products has also been reported in the US and other regions of the world. Pain relief is among many self-reported kratom effects but have not been evaluated in controlled human subject research. Methods: Kratom effects on pain tolerance were assessed in a randomized, placebo-controlled, double-blind study. During a 1-day inpatient stay, participants received a randomized sequence of kratom and placebo decoctions matched for taste and appearance. Pain tolerance was measured objectively in a cold pressor task (CPT) as time (seconds) between the pain onset and the hand withdrawal from the ice bath. Health status, vital signs, objective, and subjective indicators of withdrawal symptoms, self-reported data on lifetime kratom use patterns, and assessments of blinding procedures were also evaluated. Results: Twenty-six males with the mean (SD) age 24.3 (3.4) years were enrolled. They reported the mean (SD) 6.1 (3.2) years of daily kratom consumption. Pain tolerance increased significantly 1 hour after kratom ingestion from the mean (SD) 11.2 (6.7) seconds immediately before to 24.9 (39.4) seconds 1 hour after kratom consumption (F(2,53.7)=4.33, p=0.02). Pain tolerance was unchanged after consuming placebo drinks: 15.0 (19.0) seconds immediately before and 12.0 (8.1) seconds 1 hour after consumption of placebo (F(2,52.8)=0.93, p=0.40). No discomfort or signs of withdrawal were reported or observed during 10-20 hours of kratom discontinuation. Conclusions: Kratom decoction demonstrated a substantial and statistically significant increase in pain tolerance. Further rigorous research on kratom pain-relieving properties and a safety profile is needed.

Global strategy for New Psychoactive Substances: an update.

PURPOSE OF REVIEW: The aim of this review is to provide an update on recent trends of New Psychoactive Substances (NPS) and the current global strategies implemented to manage them. RECENT FINDINGS: The number of NPS has increased from 166 in 2009 to 892 in 2018, with about 36% having stimulant effects. Such trend revels some unprecedented patterns. The decline in the emergence of new synthetic cannabinoids has coincided with rising deaths due to overdose of fentanyl and non-fentanyl compounds in North America and Europe. The detection of new stimulant NPS has stabilized since 2015. Although the level of seizures of mephedrone have risen since then, they are still below the levels reported before international control. The legal status of kratom still remains unclear, whereas calls for research on its benefits continue. The nonmedical use of tramadol in Africa and Middle East is a cause of growing concern. SUMMARY: Although the rise of NPS is a cause for concern, evidence suggests that the strategy to face the challenge should include updating international data collection systems, integrating scientific-based interventions for drug use, strengthening national monitoring, and increasing collaborative research and forensic capabilities. The legal, regulatory framework and clinical guidelines should remain dynamic, whereas enforcement agencies should measure success by destroying drug networks as seizures rarely dismantle drug markets.

The Use of Benzodiazepines among Kratom (Mitragyna Speciosa Korth.) Users.

The leaves from Mitragyna speciosa (Korth.) trees, also known as kratom, are traditionally used in Southeast Asia as a mild psychotropic agent. We investigated the demographic characteristics of persons who used both kratom cocktail and benzodiazepines (BZO) in a sample drawn from a rural area in Penang, Malaysia, and the reasons for BZO use. Seventy-seven participants who currently use a kratom cocktail along with BZO were recruited through snowball sampling for this cross-sectional study. The participants were male, and the majority were Malays (99%, n = 76/77), single (57%, n = 44/77) and employed (91%, n = 70/77). BZO was used with kratom cocktail 1) to increase euphoria; 2) to reduce dependence on methamphetamine; 3) to promote sleep; 4) to ease methamphetamine-associated psychological symptoms and 5) to decrease the craving for kratom. There were no significant differences in the intake of kratom use (p = .751), BZO use duration (p = .259), frequency (p = .188) and quantity (p = .888) of BZO use in the last 7 days, and quantity of BZO use in the last 30 days (p = .337) between kratom users and kratom poly-drug users. An awareness of the health consequences of the co-use of kratom with BZO is needed to prevent untoward health incidents.

Long-Term Effects of Kratom (Mitragyna speciosa) Use

@#Introduction: Kratom or (Mitragyna speciosa) leaves are consumed as a folk remedy and opioid substitute in the Southeast Asian region. There is still a lack of information about the long-term or toxic-causing effects of kratom use. Methods: A total of thirteen regular kratom users, with long-term (>20 twenty years) kratom use history were recruited for this cross-sectional pilot study. Respondents were required to undergo a blood-test and laboratory anaysis was conducted to determine the mitragynine content in an acquired street sample of kratom. Results: The regular, longterm consumption of brewed kratom decoction did not cause any significant alterations in haematological, kidney, liver, thyroid, inflammatory and gastrointestinal analytes in a cohort of kratom users who had no history of substance misuse. However, those who had a higher intake (>3 glasses per day) of kratom exhibited higher lipid values (except for HDL-cholesterol), and a moderate elevation of homocysteine level. Conclusion: Long-term (>20 years with a daily intake of ≥87.54mg of mitragynine) kratom consumption was not associated with altered biochemical levels, although prolonged and heavy use (>3 glasses daily) may result in cardiovascular risks. The latter finding, however, requires further investigation.

The prevalence of psychotic symptoms in kratom (Mitragyna speciosa Korth.) Users in Malaysia.

BACKGROUND: Kratom is a traditional medicinal herb widely used in Malaysia and Thailand. Despite its widespread use and statements by regulatory agencies on the potential for kratom-associated psychosis, there is little data regarding the prevalence of psychotic symptoms among kratom users. This study investigated the prevalence of psychosis among kratom users, described psychotic symptomatology and severity, while examining associations between kratom use characteristics and the occurrence of psychotic symptoms. METHODS: This cross-sectional clinical survey recruited 150 regular kratom users. The Mini International Neuropsychiatric Interview (MINI) and Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) diagnostic criteria were used to evaluate psychotic symptomatology among kratom users, and the Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of psychiatric symptoms. Chi-square tests with Yate's correction were performed to determine the association between kratom use characteristics and the occurrence of psychotic symptoms among kratom users in this study. RESULTS: Six out of 150 kratom users (4%) presented with any psychotic symptoms. The psychotic symptoms reported were positive symptoms and thought alienation, with a mean BPRS score of 33 (i.e., mild severity). Variables related to kratom use (such as intake of kratom with diphenhydramine, duration of kratom use, and quantity and frequency of daily kratom use) were not associated with the occurrence of psychotic symptoms among kratom users. CONCLUSION: Although psychotic symptoms could occur among regular kratom users, they were rare and not significantly associated with kratom use characteristics. We found no evidence of elevated psychosis among regular users.

Effects of Kratom (Mitragyna Speciosa Korth.) Use in Regular Users.

Background: Mitragyna speciosa (Korth.) or kratom is an indigenous medicinal plant of Southeast Asia. Kratom is widely reported to have dose-dependent effects based on available literature, but to our knowledge, this has not been established conclusively. Objective: This study sought to evaluate if kratom use produces dose-dependent effects, with a stimulant effect at low doses and a sedative effect at high doses, in a sample of regular kratom users. Methods: A total of 63 regular kratom users participated in this cross-sectional study. The Brief-Biphasic Alcohol Effects Scale (B-BAES) was used to determine subjects self-report kratom use experiences. Results: Almost all in the sample were male (98%, n = 62/63), and the majority of subjects were Malays (94%, n = 59/63). The mean age of the subjects in the sample was 43.8 years (SD = 12.1). Seventy-five percent (n = 47/63) have >5 years kratom use history, and 65% (n = 41/63) consumed >3 glasses of kratom daily. Results from first test showed no significant difference in the stimulant (t61 =0.371, p < .331) and sedative effects (t61 =502, p < .759) between those who consumed >3 glasses a day or less than this amount, regardless of duration of use. In the second test, no significant differences in the mean scores were found among those who consumed >3 glasses daily or less than this amount among short-term or long-term uses. Conclusions: Daily kratom use produced both stimulant and sedative effects but they were not statistically significantly associated with the dose consumed, both among short-term and long-term users in our sample.