Displaying publications 1 - 20 of 39 in total

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  1. 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*
  2. 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*
  3. Teah MK, Chan GK, Wong MTF, Yeap TB
    BMJ Case Rep, 2021 Jan 08;14(1).
    PMID: 33419751 DOI: 10.1136/bcr-2020-238318
    Prolonged exposure to benzodiazepines (BDZ) may contribute towards physical dependence, which is manifested by iatrogenic Benzodiazepine Withdrawal Syndrome (BWS), a condition often underdiagnosed. Current evidence recommends precluding BDZ infusion as sedation in the intensive care unit to avoid possible withdrawal and delirium issues. Administration of dexmedetomidine should be considered to facilitate weaning in patients with BWS.
    Matched MeSH terms: Substance Withdrawal Syndrome/diagnosis*; Substance Withdrawal Syndrome/etiology*; Substance Withdrawal Syndrome/therapy
  4. Khoo BH
    Med J Malaysia, 1978 Jun;32(4):297-301.
    PMID: 732626
    Matched MeSH terms: Substance Withdrawal Syndrome/diagnosis*
  5. Motlagh F, Ibrahim F, Menke JM, Rashid R, Seghatoleslam T, Habil H
    J Neurosci Res, 2016 Apr;94(4):297-309.
    PMID: 26748947 DOI: 10.1002/jnr.23703
    Neuroelectrophysiological properties have been used in human heroin addiction studies. These studies vary in their approach, experimental conditions, paradigms, and outcomes. However, it is essential to integrate previous findings and experimental methods for a better demonstration of current issues and challenges in designing such studies. This Review examines methodologies and experimental conditions of neuroelectrophysiological research among heroin addicts during withdrawal, abstinence, and methadone maintenance treatment and presents the findings. The results show decrements in attentional processing and dysfunctions in brain response inhibition as well as brain activity abnormalities induced by chronic heroin abuse. Chronic heroin addiction causes increased β and α2 power activity, latency of P300 and P600, and diminished P300 and P600 amplitude. Findings confirm that electroencephalography (EEG) band power and coherence are associated with craving indices and heroin abuse history. First symptoms of withdrawal can be seen in high-frequency EEG bands, and the severity of these symptoms is associated with brain functional connectivity. EEG spectral changes and event-related potential (ERP) properties have been shown to be associated with abstinence length and tend to normalize within 3-6 months of abstinence. From the conflicting criteria and confounding effects in neuroelectrophysiological studies, the authors suggest a comprehensive longitudinal study with a multimethod approach for monitoring EEG and ERP attributes of heroin addicts from early stages of withdrawal until long-term abstinence to control the confounding effects, such as nicotine abuse and other comorbid and premorbid conditions.
    Matched MeSH terms: Substance Withdrawal Syndrome/physiopathology*
  6. 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*
  7. 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
  8. 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*
  9. Aida Maziha Z, Imran A, Azlina I, Harmy MY
    Malays Fam Physician, 2018;13(2):19-25.
    PMID: 30302179 MyJurnal
    Introduction: Nicotine cravings and withdrawal symptoms are associated with higher rates of relapse. It has been shown that combining behavioral therapy and pharmacotherapy leads to a higher long-term abstinence rate in those who quit smoking. Al-Quran recitation has been proven to reduce anxiety among athletes before tournaments and pulse and heart rates among patients awaiting cardiac operations. As most of the patients who wish to stop smoking experience high-anxiety states, we postulate that Al-Quran recitation will also able to reduce craving among smokers attempting to quit smoking.

    Methods: Fifty smokers from an outpatient clinic were randomly assigned to control and intervention groups. They were taught different ways of coping with smoking urges, i.e., counseling using the 12'M' method (control group) versus Al-Quran recitation (intervention group). They met for four consecutive weeks of counselling and to fill out a withdrawal scale. Carbon monoxide (CO) levels were tested at baseline and at week 4. At week 12, the number of cigarettes smoked was measured again. The decrease in the number of cigarettes considered to be clinically significant for the calculation of sample size was based on expert opinion.

    Results: The reduction in the number of cigarettes smoked was 7 cigarettes in the counselling group and 9 cigarettes in Al-Quran recitation group over 12 weeks duration. There was a statistically significant difference in the number of cigarettes smoked between the groups. There was also a statistically significant difference in the change in cravings between the groups at week 4 (p-value = 0.005). However, the difference in the changes in CO levels between the two groups was not statistically significant.

    Conclusion: Al-Quran recitation produced a statistically significant reduction in the number of cigarettes smoked at week 12 and a significant change in cravings at week 4 among smokers attempting to quit. Difference in smoking abstinence rates was not measured in this study.
    Matched MeSH terms: Substance Withdrawal Syndrome
  10. 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
  11. 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
  12. 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*
  13. Awaisu A, Samsudin S, Amir NA, Omar CG, Hashim MI, Mohamad MH, et al.
    PMID: 20492717 DOI: 10.1186/1471-2288-10-46
    The purpose of the linguistic validation of the Wisconsin Smoking Withdrawal Scale (WSWS) was to produce a translated version in Malay language which was "conceptually equivalent" to the original U.S. English version for use in clinical practice and research.
    Matched MeSH terms: Substance Withdrawal Syndrome*
  14. Vicknasingam B, Narayanan S, Beng GT, Mansor SM
    Int J Drug Policy, 2010 Jul;21(4):283-8.
    PMID: 20092998 DOI: 10.1016/j.drugpo.2009.12.003
    BACKGROUND: Ketum (krathom) has been mentioned in the literature as a traditional alternative to manage drug withdrawal symptoms though there are no studies indicating its widespread use for this purpose. This study examines the reasons for ketum consumption in the northern areas of peninsular Malaysia where it is widely used.
    METHODS: A cross-sectional survey of 136 active users was conducted in the northern states of Kedah and Penang in Malaysia. On-site urine screening was done for other substance use.
    FINDINGS: Ketum users were relatively older (mean 38.7 years) than the larger substance using group. Nearly 77% (104 subjects) had previous drug use history, whilst urine screening confirmed 62 subjects were also using other substances. Longer-term users (use >2 years) had higher odds of being married, of consuming more than the average three glasses of ketum a day and reporting better appetite. Short-term users had higher odds of having ever used heroin, testing positive for heroin and of using ketum to reduce addiction to other drugs. Both groups used ketum to reduce their intake of more expensive opiates, to manage withdrawal symptoms and because it was cheaper than heroin. These findings differ from those in neighbouring Thailand where ketum was used primarily to increase physical endurance.
    CONCLUSIONS: No previous study has shown the use of ketum to manage opioid withdrawal symptoms except for a single case reported in the US. Ketum was described as affordable, easily available and having no serious side effects despite prolonged use. It also permitted self-treatment that avoids stigmatisation as a drug dependent. The claims of so many subjects on the benefits of ketum merits serious scientific investigation. If prolonged use is safe, the potential for widening the scope and reach of substitution therapy and lowering its cost are tremendous, particularly in developing countries.
    Matched MeSH terms: Substance Withdrawal Syndrome/rehabilitation*
  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. 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*
  17. Zhang B, Zhang R, Deng H, Cui P, Li C, Yang F, et al.
    PLoS One, 2023;18(12):e0294768.
    PMID: 38051740 DOI: 10.1371/journal.pone.0294768
    BACKGROUND AND AIM: Primarily, this study compares the efficacy of probiotic and acceptance and commitment therapy (ACT) in alleviating the severity of alcohol craving and alcohol use disorder (AUD) among patients who had undergo two weeks of in-patient detoxification. Secondarily, this study compares the efficacy of probiotic and ACT in mitigating the severity of comorbid depression and anxiety symptoms; decreasing serum level of pro-inflammatory cytokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α); changing the event-related potential in electroencephalogram (EEG) and restoring microbiota flora in the gut of AUD patients.

    METHODS AND ANALYSIS: Initially, during Phase I of the study, the serum level of IL-1β, IL-6 and TNF-α; ERP changes in the EEG and fecal microbiota content will be compared between 120 AUD patients and 120 healthy controls. Subsequently in Phase II of the study, 120 AUD patients will be randomized by stratified permuted block randomization into the probiotic, ACT and placebo groups in a 1:1:1 ratio. Participants in the probiotic and placebo groups will be administered one sachet per day of Lactobacillus spp. probiotic and placebo, respectively for 12 weeks. While those in the ACT group will receive one session per week of ACT for 8 weeks. Outcome measures will be administered at four timepoints, such as t0 = baseline assessment prior to intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention and t3 = 24 weeks after intervention. Primary outcomes are the degrees of alcohol craving, alcohol withdrawal during abstinence and AUD. Secondary outcomes to be assessed are the severity of co-morbid depression and anxiety symptoms; the serum levels of IL-1β, IL-6 and TNF-α; changes in ERP and fecal microbiota content.

    TRIAL REGISTRATION NUMBER: NCT05830708 (ClinicalTrials.gov). Registered on April 25, 2023.

    Matched MeSH terms: Substance Withdrawal Syndrome*
  18. Khor BS, Jamil MF, Adenan MI, Shu-Chien AC
    PLoS One, 2011;6(12):e28340.
    PMID: 22205946 DOI: 10.1371/journal.pone.0028340
    A major obstacle in treating drug addiction is the severity of opiate withdrawal syndrome, which can lead to unwanted relapse. Mitragynine is the major alkaloid compound found in leaves of Mitragyna speciosa, a plant widely used by opiate addicts to mitigate the harshness of drug withdrawal. A series of experiments was conducted to investigate the effect of mitragynine on anxiety behavior, cortisol level and expression of stress pathway related genes in zebrafish undergoing morphine withdrawal phase. Adult zebrafish were subjected to two weeks chronic morphine exposure at 1.5 mg/L, followed by withdrawal for 24 hours prior to tests. Using the novel tank diving tests, we first showed that morphine-withdrawn zebrafish display anxiety-related swimming behaviors such as decreased exploratory behavior and increased erratic movement. Morphine withdrawal also elevated whole-body cortisol levels, which confirms the phenotypic stress-like behaviors. Exposing morphine-withdrawn fish to mitragynine however attenuates majority of the stress-related swimming behaviors and concomitantly lower whole-body cortisol level. Using real-time PCR gene expression analysis, we also showed that mitragynine reduces the mRNA expression of corticotropin releasing factor receptors and prodynorphin in zebrafish brain during morphine withdrawal phase, revealing for the first time a possible link between mitragynine's ability to attenuate anxiety during opiate withdrawal with the stress-related corticotropin pathway.
    Matched MeSH terms: Substance Withdrawal Syndrome/drug therapy*; Substance Withdrawal Syndrome/genetics; Substance Withdrawal Syndrome/metabolism; Substance Withdrawal Syndrome/psychology
  19. 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*
  20. 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
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