Displaying publications 1 - 20 of 39 in total

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  1. McWhirter L, Morris S
    Eur Addict Res, 2010;16(4):229-31.
    PMID: 20798544 DOI: 10.1159/000320288
    Kratom (Mitragyna speciosa) has been used for medicinal and recreational purposes. It has reported analgesic, euphoric and antitussive effects via its action as an agonist at opioid receptors. It is illegal in many countries including Thailand, Malaysia, Myanmar, South Korea and Australia; however, it remains legal or uncontrolled in the UK and USA, where it is easily available over the Internet. We describe a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. He demonstrated dependence on kratom with withdrawal symptoms consisting of anxiety, restlessness, tremor, sweating and cravings for the substance. A reducing regime of dihydrocodeine and lofexidine proved effective in treating subjective and objective measures of opioid-like withdrawal phenomena, and withdrawal was relatively short and benign. There are only few reports in the literature of supervised detoxification and drug treatment for kratom dependence. Our observations support the idea that kratom dependence syndrome is due to short-acting opioid receptor agonist activity, and suggest that dihydrocodeine and lofexidine are effective in supporting detoxification.
    Matched MeSH terms: Substance Withdrawal Syndrome/therapy*
  2. Ahmad Nabil Md Rosli, Singh, Suarn
    ASEAN Journal of Psychiatry, 2015;16(2):241-244.
    MyJurnal
    The incidence of benzodiazepine paradoxical reaction is uncommon. It may be implicated with crime as will be described in this case report. Method: We report a 37 year-old schizophrenia patient who was detained by the authority under Section 392/397 of Penal Code assaulting a lady using sharp weapon. He had history of illicit substance abuse and benzodiazepine dependence with significant history of aggression associated with benzodiazepine. Just prior to the incident, he took a significant amount of various types of benzodiazepine and suffered from amnesia of that event. During the time of the offense, he was in remission as far as schizophrenia is concerned. Result: He was under the forensic psychiatric care and observation at Hospital Bahagia Ulu Kinta (HBUK). He developed withdrawal symptoms of benzodiazepine in the ward. Conclusion: He was found by the expert team to be under the influence of benzodiazepine during the offence. The role of benzodiazepine and relevant factors leading to aggression will be discussed in this manuscript.
    Matched MeSH terms: Substance Withdrawal Syndrome
  3. Chellian R, Pandy V, Mohamed Z
    Eur J Pharmacol, 2018 Jan 05;818:10-16.
    PMID: 29042206 DOI: 10.1016/j.ejphar.2017.10.025
    In the present study, the effect α-asarone on nicotine withdrawal-induced depression-like behavior in mice was investigated. In this study, mice were exposed to drinking water or nicotine solution (10-200µg/ml) as a source of drinking for forty days. During this period, daily fluid consumption, food intake and body weight were recorded. The serum cotinine level was estimated before nicotine withdrawal. Naïve mice or nicotine-withdrawn mice were treated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) for eight consecutive days and the forced swim test (FST) or locomotor activity test was conducted. In addition, the effect of α-asarone or bupropion on the hippocampal pCREB, CREB and BDNF levels during nicotine-withdrawal were measured. Results indicated that α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment did not significantly alter the immobility time in the FST or spontaneous locomotor activity in naïve mice. However, the immobility time of nicotine-withdrawn mice was significantly attenuated with α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment in the FST. Besides, α-asarone (5, 10 and 20mg/kg, i.p.) or bupropion (10mg/kg, i.p.) pretreatment significantly attenuated the hippocampal pCREB levels in nicotine-withdrawn mice. Overall, the present results indicate that α-asarone treatment attenuated the depression-like behavior through the modulation of hippocampal pCREB levels during nicotine-withdrawal in mice.
    Matched MeSH terms: Substance Withdrawal Syndrome/psychology*
  4. Annuar NAK, Azlan UK, Mediani A, Tong X, Han R, Al-Olayan E, et al.
    Biomed Pharmacother, 2024 Feb;171:116134.
    PMID: 38219389 DOI: 10.1016/j.biopha.2024.116134
    Mitragynine is one of the main psychoactive alkaloids in Mitragyna speciosa Korth. (kratom). It has opium-like effects by acting on μ-, δ-, and κ-opioid receptors in the brain. The compound also interacts with other receptors, such as adrenergic and serotonergic receptors and neuronal Ca2+ channels in the central nervous system to have its neuropharmacological effects. Mitragynine has the potential to treat diseases related to neurodegeneration such as Alzheimer's disease and Parkinson's disease, as its modulation on the opioid receptors has been reported extensively. This review aimed to provide an up-to-date and critical overview on the neuropharmacological effects, mechanisms of action, pharmacokinetics and safety of mitragynine as a prospective psychotropic agent. Its multiple neuropharmacological effects on the brain include antinociceptive, anti-inflammatory, antidepressant, sedative, stimulant, cognitive, and anxiolytic activities. The potential of mitragynine to manage opioid withdrawal symptoms related to opioid dependence, its pharmacokinetics and toxic effects were also discussed. The interaction of mitragynine with various receptors in the brain produce diverse neuropharmacological effects, which have beneficial properties in neurological disorders. However, further studies need to be carried out on mitragynine to uncover its complex mechanisms of action, pharmacokinetics, pharmacodynamic profiles, addictive potential, and safe dosage to prevent harmful side effects.
    Matched MeSH terms: Substance Withdrawal Syndrome*
  5. Harun N, Johari IS, Mansor SM, Shoaib M
    Psychopharmacology (Berl), 2020 Mar;237(3):855-867.
    PMID: 31832720 DOI: 10.1007/s00213-019-05418-6
    RATIONALE: Kratom is proposed to exhibit therapeutic potential as an opium substitute, but little is known about its dependence-producing profile, particularly of its main psychoactive compound, mitragynine (MG).

    OBJECTIVES: This study examined the dependence-producing effects of MG using operant-scheduled behaviour in rats and investigated the potential therapeutic effect of MG by comparing effects to buprenorphine in morphine-dependent rats using the same schedule-controlled behavioural task.

    METHODS: The effects of acutely administered MG and morphine were determined in rats trained to respond under fixed-ratio (FR) 10 schedule of food reinforcement. Next, the rats were administered MG and morphine twice daily for 14 consecutive days to determine if physiological dependence would develop by examining cessation of drug treatment and following antagonist-precipitated withdrawal. The study then examined the effects of MG substitution to suppress naloxone-precipitated morphine withdrawal effects on scheduled responding.

    RESULTS: Acute doses of MG did not produce dose-related decreases on FR schedules of responding compared to morphine. Unlike morphine, MG-treated rats showed no suppression of response rates following cessation of MG treatment. However, withdrawal effects were evident for MG after precipitation by either naloxone or SR141716A (rimonabant), similar to morphine-treated rats. MG in higher doses (10 and 30 mg/kg) attenuated the naloxone-precipitated morphine withdrawal effects while smaller doses of buprenorphine (0.3 and 1.0 mg/kg) were necessary to alleviate these effects.

    CONCLUSION: The findings suggest that MG does not induce physiological dependence but can alleviate the physical symptoms associated with morphine withdrawal which represent the desired characteristics of novel pharmacotherapeutic interventions for managing opioid use disorder (OUD).

    Matched MeSH terms: Substance Withdrawal Syndrome/physiopathology; Substance Withdrawal Syndrome/psychology*
  6. Chean KY, Goh LG, Liew KW, Tan CC, Choi XL, Tan KC, et al.
    BMJ Open, 2019 07 09;9(7):e025491.
    PMID: 31289057 DOI: 10.1136/bmjopen-2018-025491
    OBJECTIVES: This qualitative study aims to construct a model of the barriers to smoking cessation in the primary care setting.

    DESIGN: Individual in-depth, semistructured interviews were audio-taped, then verbatim transcribed and translated when necessary. The data were first independently coded and then collectively discussed for emergent themes using the Straussian grounded theory method.

    PARTICIPANTS AND SETTING: Fifty-seven current smokers were recruited from a previous smoking related study carried out in a primary care setting in Malaysia. Current smokers with at least one failed quit attempts were included.

    RESULTS: A five-theme model emerged from this grounded theory method. (1) Personal and lifestyle factors: participants were unable to resist the temptation to smoke; (2) Nicotine addiction: withdrawal symptoms could not be overcome; (3) Social cultural norms: participants identified accepting cigarettes from friends as a token of friendship to be problematic; (4) Misconception: perception among smokers that ability to quit was solely based on one's ability to achieve mind control, and perception that stopping smoking will harm the body and (5) Failed assisted smoking cessation: smoking cessation services were not felt to be user-friendly and were poorly understood. The themes were organised into five concentric circles based on time frame: those actionable in the short term (themes 1 and 2) and the long term (themes 3, 4, 5).

    CONCLUSIONS: Five themes of specific beliefs and practices prevented smokers from quitting. Clinicians need to work on these barriers, which can be guided by the recommended time frames to help patients to succeed in smoking cessation.

    Matched MeSH terms: Substance Withdrawal Syndrome
  7. Lee CH, Chiang SL, Ko AM, Hua CH, Tsai MH, Warnakulasuriya S, et al.
    Addiction, 2014 Jul;109(7):1194-204.
    PMID: 24650227 DOI: 10.1111/add.12530
    Betel-quid (BQ) contains biologically psychoactive ingredients; however, data are limited concerning the symptoms and syndrome of BQ dependence among chewers. The aims of this study were to evaluate the ingredients-associated BQ dependence syndrome and country-specific chewing features and behaviour for BQ dependence among chewers from six Asian communities.
    Matched MeSH terms: Substance Withdrawal Syndrome/epidemiology
  8. Nabipour S, Ayu Said M, Hussain Habil M
    Iran J Public Health, 2014 Aug;43(8):1022-32.
    PMID: 25927032
    Addiction to the illicit and prescribed use of opiate is an alarming public health issue. Studies on addictive disorders have demonstrated severe nutritional deficiencies in opiate abusers with behavioral, physiological and cognitive symptoms. Opiate addiction is also link with a significant number of diseases including Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and other blood borne diseases generally stem from the use of needles to inject heroin. The use of medication assisted treatment for opioid addicts in combination with behavioural therapies has been considered as a highly effective treatment. Methadone is a long-lasting μ-opioid agonist and a pharmacological tool which attenuates withdrawal symptoms effectively replacement therapies. This review article aims to explain opiate addiction mechanisms, epidemiology and disease burden with emphasis on dietary and nutritional status of opiate dependent patients in methadone maintenance therapy.
    Matched MeSH terms: Substance Withdrawal Syndrome
  9. Khadijah Hasanah, A.A., Aia Harlina, A.R., Nik Ruzyanei, N.J.
    MyJurnal
    Evidence linking cannabis use and depression remains inconsistent. Variations of clinical features were observed in those with history of cannabis use presented with affective symptoms. We report a case of a 19-year-old male college student with a history of heavy cannabis use for at least seven months. A month after stopping cannabis, he presented with severe persistent depressive symptoms. He had no withdrawal symptoms prior to this. He had severe depressive symptoms with melancholic features and progressed to multiple and serious suicidal attempts. While the use of cannabis is implicated in neither the patient’s diagnosis nor management, its use has a significant role in influencing the clinical features and course of the illness. This case suggests that depression can start long after cessation of cannabis use with the history of cannabis remained as a significant risk factor.
    Matched MeSH terms: Substance Withdrawal Syndrome
  10. Singh D, Narayanan S, Vicknasingam B, Corazza O, Santacroce R, Roman-Urrestarazu A
    Hum Psychopharmacol, 2017 05;32(3).
    PMID: 28544011 DOI: 10.1002/hup.2582
    OBJECTIVE: Kratom (Mitragyna speciosa. Korth) is an indigenous medicinal plant of Southeast Asia. This review paper aims to describe the trends of kratom use in Southeast Asia.

    DESIGN: A literature review search was conducted through ScienceDirect, Scopus, ProMed and Google Scholar. Twenty-five articles illustrating kratom use in humans in Southeast Asia were reviewed.

    RESULTS: Kratom has long been used by rural populations in Southeast Asia as a remedy for common ailments, to fight fatigue from hard manual work, as a drink during social interaction among men, and in village religious functions. Studies based on self-reports suggest that prolonged kratom use does not result in serious health risks or impair social functioning. Two recent trends have also emerged: (a) Kratom is reportedly being used to ease withdrawal from opioid dependence in rural settings; whereas (b) in urban areas, adulterated kratom cocktails are being consumed by younger people to induce euphoria.

    CONCLUSIONS: Legal sanctions appear to have preceded serious scientific investigations into the claimed benefits of ketum. More objective-controlled trials and experiments on humans need to be conducted to validate self-report claims by kratom users in the community.

    Matched MeSH terms: Substance Withdrawal Syndrome/diagnosis; Substance Withdrawal Syndrome/drug therapy*; Substance Withdrawal Syndrome/epidemiology*
  11. George A, Udani JK, Yusof A
    Pharm Biol, 2019 Dec;57(1):145-153.
    PMID: 30922154 DOI: 10.1080/13880209.2019.1585460
    CONTEXT: Phyllanthus amarus Schumach. and Thonn. (Euphorbiaceae) is traditionally known to improve general liver health. However, its effect on hangover is unknown.

    OBJECTIVE: This study evaluated PHYLLPRO™, a standardized ethanol extract of P. amarus leaves for protection against oxidative stress and recovery from hangover symptoms.

    MATERIAL AND METHODS: Ten days daily oral supplementation of 750 mg/day followed by intoxication was evaluated in a randomized placebo-controlled (containing only excipient), crossover study in 15 subjects (21-50 years old), for oxidative stress, liver damage, alleviating hangover symptoms (Hangover Severity Score: HSS) and mood improvement (Profile-of-Mood-Scores: POMS).

    RESULTS: PHYLLPRO™ was able to remove blood alcohol in the active group while the placebo group still had 0.05% at 12 h post-intoxication (p  0.05) from baseline to hour 22 was reported in the placebo group using POMS. Significant anti-inflammatory group effect favouring the active group, by the upregulation of cytokines IL-8 (p = 0.0014) and IL-10 (p = 0.0492) and immunomodulatory effects via IL-12p70 (p = 0.0304) were observed. The incidence of adverse events was similar between groups indicating the safety of PHYLLPRO™.

    DISCUSSION AND CONCLUSION: Preliminary findings of PHYLLPRO™ in managing hangover, inflammation and liver functions following intoxication, is demonstrated. Future studies on PHYLLPRO™ in protecting against oxidative stress and hangover in larger populations is warranted.

    Matched MeSH terms: Substance Withdrawal Syndrome/drug therapy*; Substance Withdrawal Syndrome/etiology
  12. Fernandez DP, Kuss DJ, Justice LV, Fernandez EF, Griffiths MD
    Arch Sex Behav, 2023 May;52(4):1819-1840.
    PMID: 36652136 DOI: 10.1007/s10508-022-02519-w
    Little is known about whether withdrawal-like symptoms manifest when regular pornography users attempt to abstain from pornography. The present study used a randomized controlled design to examine whether (1) negative abstinence effects that may be potentially reflective of withdrawal-related symptoms manifest when a non-clinical sample of regular pornography users attempt to abstain from pornography for a 7-day period and (2) these negative abstinence effects would only manifest (or manifest more strongly) for those with higher levels of problematic pornography use (PPU). A total of 176 undergraduate students (64.2% female) who were regular pornography users (defined as having used pornography ≥ three times a week in the past 4 weeks) were randomly assigned to an abstinence group (instructed to attempt abstinence from pornography for 7 days, n = 86) or a control group (free to watch pornography as usual, n = 90). Participants completed measures of craving, positive and negative affect, and withdrawal symptoms at baseline and each night of the 7-day period. Contrary to the confirmatory hypotheses, there were no significant main effects of group (abstinence vs. control) or group × PPU interaction effects on any of the outcome measures, controlling for baseline scores. These findings indicate that no evidence of withdrawal-related symptoms was found for abstaining participants, and this was not dependent on level of PPU. However, exploratory analyses showed a significant three-way interaction (group × PPU × past 4-week frequency of pornography use [FPU]) on craving, where an abstinence effect on craving was found at high levels of PPU only once past 4-week FPU reached the threshold of daily use. While these exploratory findings should be interpreted with caution, they suggest that abstinence effects could potentially manifest when there is a combination of high PPU and high FPU-a hypothesis that warrants investigation in future prospective abstinence studies.
    Matched MeSH terms: Substance Withdrawal Syndrome*
  13. Kumar J, Hapidin H, Bee YT, Ismail Z
    Behav Brain Funct, 2013;9:43.
    PMID: 24279870 DOI: 10.1186/1744-9081-9-43
    Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.
    Matched MeSH terms: Substance Withdrawal Syndrome/drug therapy*
  14. Chandrasekaran PK
    Singapore Med J, 2008 Jun;49(6):e166-7.
    PMID: 18581012
    Insomnia and depression are frequently encountered in patients during withdrawal from substances. While there are no approved medications for treating them, off-label attempts to address these phenomena with mirtazapine have shown some promising results. This case describes the use of mirtazapine as an aid in benzodiazepine withdrawal and its potential benefits in alleviating insomnia and depression in a 32-year-old man. It was found to ameliorate sleep myoclonus that was thought to be associated with his withdrawal syndrome. It is hoped this report will generate interest and stimulate further research in this area of psychopharmacology.
    Matched MeSH terms: Substance Withdrawal Syndrome/drug therapy*
  15. Rahman A, Nik Mohamed MH, Mahmood S
    J Pharm Pharm Sci, 2021;24:200-209.
    PMID: 33909555 DOI: 10.18433/jpps31243
    PURPOSE: Evidence for the complete nicotine cessation is inadequate among electronic cigarettes (ECs) single users (SUs, use only ECs), and dual users (DUs, use both ECs and conventional cigarettes (CCs). The primary aim of this study was to evaluate the nicotine cessation among SUs and DUs who used ECs over one year.

    METHODS: We observed 70 SUs and 148 DUs for 52 weeks and tested their exhaled carbon monoxide and saliva cotinine to confirm their complete nicotine cessation status through cotinine in saliva. Safety issues were to be identified through self-report. Smoking cessation, CCs reduction of ≥ 50%, and relapsed to CCs smoking and safety issues were also documented.

    RESULTS: The nicotine cessation rate was higher in SUs then DUs (15.9% vs. 6.8%; P = 0.048; 95% CI (2.328-0.902). A similar result for smoking cessation (34.8% SUs vs. 17.1% DUs; P = 0.005; 95% CI: 2.031-0.787), whereas CCs ≥ 50% reduction was 23.3% DUs vs 21.7% SUs (P = 0.863; 95% CI :1.020-0.964). Relapse to CC smoking was 47.3% in DUs versus 30.4% in SUs (P = 0.026; 95% CI: 1.555-0.757). The adverse effects reported were coughing and breathing problems, whereas craving smoking was documented as a major withdrawal symptom. Smoking-related diseases were also identified, five in DUs and two in SUs, during the one-year study period.

    CONCLUSIONS: Study showed SUs achieved higher complete nicotine and smoking cessation rates as compared to DUs. However, the rates of reduced CC use were not different between both the groups. No serious adverse effects related to the sole use of ECs were detected. However, the safety of the sole use of ECs in absolute terms needs to be further validated in different populations.

    Matched MeSH terms: Substance Withdrawal Syndrome/epidemiology*
  16. Blebil AQ, S Sulaiman SA, A Hassali M, Dujaili JA, Zin AM
    Value Health Reg Issues, 2014 May;3:19-23.
    PMID: 29702926 DOI: 10.1016/j.vhri.2013.09.001
    OBJECTIVES: Assessment of nicotine withdrawal symptoms is an essential part of tobacco dependence treatment. This study aimed to evaluate the psychometric properties of a Malay translated version of the Minnesota Nicotine Withdrawal Scale (MNWS).

    METHODS: The original scale was translated into Malay following the standard guidelines proposed for translation studies. The reliability and validity of the Malay version scale were evaluated on the basis of data collected from 133 participants. The Cronbach's alpha coefficient was calculated to assess the reliability. To validate the psychometric properties of the scale, factor analysis and construct validity were used. This study was conducted at the Quit Smoking Clinic at Penang General Hospital, Penang, Malaysia.

    RESULTS: The translated scale has excellent reliability, with total Cronbach's alpha of 0.91. The test-retest reliability for the scale presented an excellent reliability and stability of the translated scale with Spearman's rank correlation coefficient (r = 0.876; P < 0.001). There was a significant positive correlation between the exhaled carbon monoxide level, Fagerstrom Test for Nicotine Dependence total score, and number of cigarettes smoked per day and the MNWS total score (r = 0.72, 0.68, and 0.68, respectively; P < 0.001). A principal-components analysis with orthogonal rotation yielded a unidimensional model that includes all the items of the MNWS.

    CONCLUSIONS: The Malay version of the MNWS is a reliable and valid measure of withdrawal symptoms as well as the smoking urge, and it is applicable to clinical practice and research study.

    Study site: Quit Smoking Clinic at Penang General Hospital, Penang, Malaysia.
    Matched MeSH terms: Substance Withdrawal Syndrome
  17. Suhaimi FW, Zul Aznal AN, Mohamad Nor Hazalin NA, Teh LK, Hassan Z, Salleh MZ
    Behav Brain Res, 2023 May 28;446:114411.
    PMID: 36997094 DOI: 10.1016/j.bbr.2023.114411
    Kratom (M. speciosa Korth) is an herbal plant native to Southeast Asia. The leaves have been widely used to alleviate pain and opioid withdrawal symptoms. However, the increasing trend of recreational use of kratom among youth is concerning because substance abuse may render the adolescent brain more susceptible to neuropathological processes, causing dramatic consequences that persist into adulthood. Therefore, the present study aimed to investigate the long-term effects of mitragynine, the main alkaloid and lyophilized kratom decoction (LKD) exposure during adolescence on cognitive behaviours and brain metabolite profiles in adult rats. Adolescent male Sprague-Dawley rats were given mitragynine (3, 10 or 30 mg/kg) or LKD orally for 15 consecutive days during postnatal days 31-45 (PND31-45). Behavioural testing was performed during adulthood (PND70-84) and the brains were subjected to metabolomic analysis. The results show that a high dose of mitragynine impaired long-term object recognition memory. Social behaviour and spatial learning were not affected, but both mitragynine and LKD impaired reference memory. Brain metabolomic study revealed several altered metabolic pathways that may be involved in the cognitive behavioural effects of LKD and mitragynine exposure. These pathways include arachidonic acid, taurine and hypotaurine, pantothenate and CoA biosynthesis, and tryptophan metabolism, while the N-isovalerylglycine was identified as the potential biomarker. In summary, adolescent kratom exposure can cause long-lasting cognitive behavioural deficits and alter brain metabolite profiles that are still evident in adulthood. This finding also indicates that the adolescent brain is vulnerable to the impact of early kratom use.
    Matched MeSH terms: Substance Withdrawal Syndrome*
  18. 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.
    Matched MeSH terms: Substance Withdrawal Syndrome/diagnosis; Substance Withdrawal Syndrome/epidemiology*; Substance Withdrawal Syndrome/psychology
  19. Prozialeck WC, Avery BA, Boyer EW, Grundmann O, Henningfield JE, Kruegel AC, et al.
    Int J Drug Policy, 2019 08;70:70-77.
    PMID: 31103778 DOI: 10.1016/j.drugpo.2019.05.003
    Kratom (Mitragyna speciosa) is a tree-like plant indigenous to Southeast Asia. Its leaves, and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. Evidence suggests kratom is being increasingly used by people in the United States and Europe for the self-management of opioid withdrawal and treatment of pain. Recent studies have confirmed that kratom and its chemical constituents have potentially useful pharmacological actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule I Controlled Substances, a move that triggered a massive response from pro-kratom advocates. The debate regarding the risks, and benefits and safety of kratom continues to intensify. Kratom proponents tout kratom as a safer and less addictive alternative to opioids for the management of pain and opioid addiction. The anti-kratom faction argues that kratom, itself, is a dangerous and addictive drug that ought to be banned. Given the widespread use of kratom and the extensive media attention it is receiving, it is important for physicians, scientists and policy makers to be knowledgeable about the subject. The purpose of this commentary is to update readers about recent developments and controversies in this rapidly evolving area. All of the authors are engaged in various aspects of kratom research and it is our intention to provide a fair and balanced overview that can form the basis for informed decisions on kratom policy. Our conclusions from these analyses are: (a) User reports and results of preclinical studies in animals strongly suggest that kratom and its main constituent alkaloid, mitragynine may have useful activity in alleviating pain and managing symptoms of opioid withdrawal, even though well-controlled clinical trials have yet to be done. (b) Even though kratom lacks many of the toxicities of classic opioids, there are legitimate concerns about the safety and lack of quality control of purported "kratom" products that are being sold in the US. (c) The issues regarding the safety and efficacy of kratom and its mitragynine constituent can only be resolved by additional research. Classification of the Mitragyna alkaloids as Schedule I controlled substances would substantially impede this important research on kratom.
    Matched MeSH terms: Substance Withdrawal Syndrome/drug therapy
  20. Bruce RD, Govindasamy S, Sylla L, Kamarulzaman A, Altice FL
    Am J Drug Alcohol Abuse, 2009;35(2):68-72.
    PMID: 19212931 DOI: 10.1080/00952990802585406
    Diversion of buprenorphine (BPN) has been described in settings where it is legally prescribed and has resulted in increasing concern. To address this concern, co-formulation of buprenorphine/naloxone (BPN/NLX) replaced buprenorphine alone in Malaysia in December 2006.
    Matched MeSH terms: Substance Withdrawal Syndrome/epidemiology
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