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Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users

Singh D, Müller CP, Vicknasingam BK

Drug Alcohol Depend, 2014 Jun 1;139:132-7.
PMID: 24698080 DOI: 10.1016/j.drugalcdep.2014.03.017

BACKGROUND: Kratom (Mitragyna speciosa) preparations have been traditionally used in Southeast Asia for its medicinal properties. Lately, Kratom use has spread to Europe and the US, where abuse potential and health hazards increasingly emerge. This study is the first to measure systematically Kratom dependence, withdrawal symptoms, and drug craving in regular Kratom users in Malaysia.
METHODS: A cross-sectional survey of 293 regular Kratom users was conducted in the community across three northern peninsular states of Malaysia. The Leeds Dependence Questionnaire, Marijuana Withdrawal Checklist, and Marijuana Craving Questionnaire-Short Form were used to measure Kratom dependence, withdrawal and craving.
RESULTS: More than half of the regular users (>6 month of use) developed severe Kratom dependence problems, while 45% showed a moderate Kratom dependence. Physical withdrawal symptoms commonly experienced include muscle spasms and pain, sleeping difficulty, watery eyes/nose, hot flashes, fever, decreased appetite, and diarrhoea. Psychological withdrawal symptoms commonly reported were restlessness, tension, anger, sadness, and nervousness. The average amount of the psychoactive compound, mitragynine, in a single dose of a Kratom drink was 79mg, suggesting an average daily intake of 276.5mg. Regular users who consumed ≥3 glasses Kratom per day, had higher odds of developing severe Kratom dependence, withdrawal symptoms, and inability to control Kratom craving.
CONCLUSIONS: The findings from this study show that regular Kratom use is associated with drug dependency, development of withdrawal symptoms, and craving. These symptoms become more severe with prolonged use and suggest a stronger control of the drug.
Social Functioning of Kratom (Mitragyna speciosa) Users in Malaysia

Singh D, Müller CP, Vicknasingam BK, Mansor SM

J Psychoactive Drugs, 2015 5 8;47(2):125-31.
PMID: 25950592 DOI: 10.1080/02791072.2015.1012610

Kratom (Mitragyna speciosa) is an indigenous plant known for its traditional medicinal use, and for its addiction potential, in Southeast Asia. In recent years, kratom and its major alkaloid, mitragynine, spread worldwide with largely unknown effects on behavior and mental health. Recent studies show that kratom use can lead to dependence and that mitragynine works as an addictive drug in animal studies. Nevertheless, kratom preparations were also suggested as a less harmful substitute in opiate withdrawal. Potential side-effects of prolonged kratom use, however, are currently unclear. The aim of this study was to investigate the social functioning of regular kratom users in Malaysia. A cross-sectional survey was carried out in three northern states of Peninsular Malaysia investigating 293 regular kratom consumers using the Addiction Severity Index in a snowball sampling technique. Findings showed that regular kratom users do not experience major impairments in their social functioning, despite being dependent on kratom for prolonged periods. Our findings suggest that chronic kratom administration does not significantly impair social functioning of users in a natural context in Malaysia.
Drug Abuse, HIV, and HCV in Asian Countries

Hser YI, Liang D, Lan YC, Vicknasingam BK, Chakrabarti A

J Neuroimmune Pharmacol, 2016 09;11(3):383-93.
PMID: 27000123 DOI: 10.1007/s11481-016-9665-x

Drug abuse and co-occurring infections are associated with significant morbidity and mortality. Asian countries are particularly vulnerable to the deleterious consequences of these risks/problems, as they have some of the highest rates of these diseases. This review describes drug abuse, HIV, and hepatitis C (HCV) in Asian countries. The most commonly used illicit drugs include opioids, amphetamine-type stimulants (ATS), cannabis, and ketamine. Among people who inject drugs, HIV rates range from 6.3 % in China to 19 % in Malaysia, and HCV ranges from 41 % in India and Taiwan to 74 % in Vietnam. In the face of the HIV epidemics, drug policies in these countries are slowly changing from the traditional punitive approach (e.g., incarcerating drug users or requiring registration as a drug user) to embrace public health approaches, including, for example, community-based treatment options as well as harm reduction approaches to reduce needle sharing and thus HIV transmission. HIV and HCV molecular epidemiology indicates limited geographic diffusion. While the HIV prevalence is declining in all five countries, use of new drugs (e.g., ATS, ketamine) continues to increase, as well as high-risk sexual behaviors associated with drug use-increasing the risk of sexual transmission of HIV, particularly among men who have sex with men. Screening, early intervention, and continued scaling up of therapeutic options (drug treatment and recovery support, ART, long-term HIV and HCV care for drug users) are critical for effective control or continued reduction of drug abuse and co-infections.
Severity of Pain and Sleep Problems during Kratom (Mitragyna speciosa Korth.) Cessation among Regular Kratom Users

Singh D, Narayanan S, Vicknasingam BK, Prozialeck WC, Ramanathan S, Zainal H, et al.

J Psychoactive Drugs, 2018 03 20;50(3):266-274.
PMID: 29558272 DOI: 10.1080/02791072.2018.1443234

Kratom (Mitragyna speciosa Korth.) is traditionally used in Southeast Asia for its medicinal value and psychoactive properties. Nonetheless, cessation from regular kratom use is reported to cause unpleasant dose-dependent withdrawal symptoms. This study aims to evaluate the severity of pain and sleep problems following the cessation of kratom tea/juice consumption among regular kratom users. A total of 170 regular users were recruited through snowball sampling for this cross-sectional study. The Brief Pain Inventory (BPI) and Pittsburgh Sleep Quality Index (PSQI) scales were administered to assess the severity of pain and sleep problems. Most participants experienced moderate pain intensity (84%) and moderate pain interference (70%) during kratom cessation; 46% experienced more sleep problems during kratom cessation. Individuals who consumed ≥4 glasses of kratom tea/juice (about 76-115 mg of mitragynine) daily had higher odds of reporting some pain interference (OR: 2.0; CI: 1.04-3.93: p
Fulltext Early Initiation of Amphetamine-Type Stimulants (ATS) Use Associated with Lowered Cognitive Performance among Individuals with Co-Occurring Opioid and ATS Use Disorders in Malaysia

Chooi WT, Mohd Zaharim N, Desrosiers A, Ahmad I, Yasin MAM, Syed Jaapar SZ, et al.

J Psychoactive Drugs, 2017 06 29;49(4):326-332.
PMID: 28661714 DOI: 10.1080/02791072.2017.1342152

Amphetamine-type stimulants (ATS) use is increasingly prevalent in Malaysia, including among individuals who also use opioids. We evaluated cognitive functioning profiles among individuals with co-occurring opioid and ATS dependence and their lifetime patterns of drug use. Participants (N = 50) enrolling in a clinical trial of buprenorphine/naloxone treatment with or without atomoxetine completed the Raven's Standard Progressive Matrices, Rey-Osterrieth Complex Figure Test, Digit Span, Trail Making and Symbol Digit Substitution tasks. Multidimensional scaling and a K-means cluster analyses were conducted to classify participants into lower versus higher cognitive performance groups. Subsequently, analyses of variance procedures were conducted to evaluate between group differences on drug use history and demographics. Two clusters of individuals with distinct profiles of cognitive performance were identified. The age of ATS use initiation, controlling for the overall duration of drug use, was significantly earlier in the lower than in the higher cognitive performance cluster: 20.9 (95% CI: 18.0-23.8) versus 25.2 (95% CI: 22.4-28.0, p = 0.038). While adverse effects of ATS use on cognitive functioning can be particularly pronounced with younger age, potentially related to greater vulnerability of the developing brain to stimulant and/or neurotoxic effects of these drugs, the current study findings cannot preclude lowered cognitive performance before initiation of ATS use.
Severity of Kratom (Mitragyna speciosa Korth.) Psychological Withdrawal Symptoms

Singh D, Narayanan S, Müller CP, Swogger MT, Rahim AA, Leong Bin Abdullah MFI, et al.

J Psychoactive Drugs, 2018 08 28;50(5):445-450.
PMID: 30152738 DOI: 10.1080/02791072.2018.1511879

Kratom leaves (Mitragyna speciosa Korth.) are traditionally used in Southeast Asia for their medicinal value. Self-report studies suggest that cessation from chronic kratom tea consumption (freshly brewed kratom tea) was associated with unpleasant psychological symptoms. This study sought to assess the severity of anxiety and depression during kratom cessation. Regular kratom users (N = 150) were recruited from the northern state of Penang (Malaysia) for this retrospective study. The Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) scales were used to assess the severity of the symptoms of anxiety and depression. Most respondents (70%) experienced symptoms of mild anxiety, while 81% experienced symptoms of mild depression during kratom cessation. Those who consumed higher quantities of kratom tea daily (≥4 glasses) had higher odds of reporting longer duration of kratom use history (OR = 4.8, 95% CI 2.3 -10.1, p
Evaluating the hematological and clinical-chemistry parameters of kratom (Mitragyna speciosa) users in Malaysia

Singh D, Müller CP, Murugaiyah V, Hamid SBS, Vicknasingam BK, Avery B, et al.

J Ethnopharmacol, 2018 Mar 25;214:197-206.
PMID: 29248450 DOI: 10.1016/j.jep.2017.12.017

ETHNOPHARMACOLOGICAL RELEVANCE: Kratom (Mitragyna speciosa Korth.) from the Rubiaceae family is an indigenous tropical medicinal tree of Southeast Asia. Kratom leaves have been used for decades in Malaysia and Thailand in traditional context for its perceived vast medicinal value, and as a mild stimulant among manual labourers. Kratom consumption has been reported to cause side-effects in kratom users.
AIM OF THE STUDY: To evaluate kratom's effects towards hematological and clinical-chemistry parameters among regular kratom users in Malaysia.
METHODS: A total of 77 subjects (n=58 regular kratom users, and n=19 healthy controls) participated in this cross-sectional study. All the surveys were conducted through face-to-face interview to elicit subject's socio-demographic characteristics and kratom use history. A full-blood test was also administered. Laboratory analysis was conducted using GC-MS to determine mitragynine content in the acquired kratom samples in order to relate mitragynine consumption with possible alterations in the blood parameters of kratom users.
RESULTS: Findings showed that there were no significant differences in the hematological and clinical-chemistry parameters of traditional kratom users and healthy controls, except for HDL and LDL cholesterol values; these were found to be above the normal reference range for the former. Similarly, long-term kratom consumption (>5 years), and quantity of daily kratom use (≥3 ½ glasses; mitragynine content 76.3-114.8mg) did not appear to alter the hematological and biochemical parameters of kratom users.
CONCLUSION: These data suggest that even long-term and heavy kratom consumption did not significantly alter the hematological and clinical-chemistry parameters of kratom users in a traditional setting.
Fulltext Atomoxetine for amphetamine-type stimulant dependence during buprenorphine treatment: A randomized controlled trial

Schottenfeld RS, Chawarski MC, Sofuoglu M, Chooi WT, Zaharim NM, M Yasin MA, et al.

Drug Alcohol Depend, 2018 05 01;186:130-137.
PMID: 29573648 DOI: 10.1016/j.drugalcdep.2018.01.017

BACKGROUND: Amphetamine type stimulants (ATS) use is highly prevalent and frequently co-occurs with opioid dependence in Malaysia and Asian countries. No medications have established efficacy for treating ATS use disorder. This study evaluated the safety, tolerability, and potential efficacy of atomoxetine for treating ATS use disorder.
METHODS: Participants with opioid and ATS dependence (N = 69) were enrolled in a pilot, double-blind, placebo-controlled randomized clinical trial; all received buprenorphine/naloxone and behavioral counseling and were randomized to atomoxetine 80 mg daily (n = 33) or placebo (n = 33). The effect size of the between-group difference on the primary outcome, proportion of ATS-negative urine tests, was estimated using Cohen's d for the intention-to-treat (ITT) sample and for higher adherence subsample (≥60 days of atomoxetine or placebo ingestion).
RESULTS: Participants were all male with mean (SD) age 39.4 (6.8) years. The proportion of ATS-negative urine tests was higher in atomoxetine- compared to placebo-treated participants: 0.77 (0.63-0.91) vs. 0.67 (0.53-0.81, d = 0.26) in the ITT sample and 0.90 (0.75-1.00) vs. 0.64 (0.51-0.78, d = 0.56) in the higher adherence subsample. The proportion of days abstinent from ATS increased from baseline in both groups (p 
From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction

Hassan Z, Muzaimi M, Navaratnam V, Yusoff NH, Suhaimi FW, Vadivelu R, et al.

Neurosci Biobehav Rev, 2013 Feb;37(2):138-51.
PMID: 23206666 DOI: 10.1016/j.neubiorev.2012.11.012

Kratom (or Ketum) is a psychoactive plant preparation used in Southeast Asia. It is derived from the plant Mitragyna speciosa Korth. Kratom as well as its main alkaloid, mitragynine, currently spreads around the world. Thus, addiction potential and adverse health consequences are becoming an important issue for health authorities. Here we reviewed the available evidence and identified future research needs. It was found that mitragynine and M. speciosa preparations are systematically consumed with rather well defined instrumentalization goals, e.g. to enhance tolerance for hard work or as a substitute in the self-treatment of opiate addiction. There is also evidence from experimental animal models supporting analgesic, muscle relaxant, anti-inflammatory as well as strong anorectic effects. In humans, regular consumption may escalate, lead to tolerance and may yield aversive withdrawal effects. Mitragynine and its derivatives actions in the central nervous system involve μ-opioid receptors, neuronal Ca²⁺ channels and descending monoaminergic projections. Altogether, available data currently suggest both, a therapeutic as well as an abuse potential.