Methadone use for acute opioid withdrawal in Tshwane shelters during the COVID-19 lockdown

Background: Temporary shelters were established for street-based people during the national level 5 coronavirus disease 2019 (COVID-19) lockdown. However, street-based substance users' need to access substances was not addressed, resulting in large numbers of people experiencing withdrawal. The Community Oriented Substance Use Programme (COSUP) in Tshwane provided methadone to manage opioid withdrawal. Methods: A cross-sectional, descriptive study was conducted using the daily methadone dosing records from shelters in Tshwane between March 2020 and September 2020. Results: The final analysis included 495 participants, of which 64 (12.9%) were initiated on 20 mg ­ 30 mg of methadone, 397 (80.2%) on 40 mg ­ 50 mg, and 34 (6.9%) on 60 mg ­ 70 mg. A total of 194 (39.2%) participants continued their initiation dose for 1­2 months, after which 126 (64.9%) had their doses increased, and 68 (35.1%) had their doses decreased. Approximately 12 (2.4%) participants were weaned off methadone after 1­3 months and 46 (9.3%) after 4­6 months. In all, 100 (20.2%) participants left the shelter prematurely and did not continue with methadone. A total of 126 (25.5%) participants continued to stay in the shelters and received methadone for 6 months, with 125 (25.3%) participants leaving the shelter with continued follow-up at a COSUP site. Conclusion: This study demonstrates variability in methadone dosing regimens among shelter residents. As the lockdown measures eased, many chose to leave the shelters, while others remained to receive methadone and other services. The COSUP appears to be effective during periods of increased vulnerability, since a large number of participants were successfully followed up. Contribution: Opioid dependence is a persistent, lifelong disease. It is multifaceted with complex environmental and individual determinants. This study highlighted the use of opioid substitution therapy during a period of increased vulnerability.

Managing acute opioid withdrawal with tramadol during COVID-19 lockdown in a peri-urban setting

Background: The coronavirus disease 2019 (COVID-19) has highlighted the scope of heroin dependence and need for evidence-based treatment amongst marginalised people in South Africa. Acute opioid withdrawal management without maintenance therapy carries risks of increased morbidity and mortality. Due to the high costs of methadone, Tshwane's Community Oriented Substance Use Programme (COSUP) used tramadol for opioid withdrawal management during the initial COVID-19 response. Aim: To describe demographics, route of heroin administration and medication-related experiences amongst people accessing tramadol for treatment of opioid withdrawal.Setting: Three community-based COSUP sites in Mamelodi (Tshwane, South Africa). Methods: A retrospective cross-sectional study was conducted. Data were collected using an interviewer-administered paper-based tool between April and August 2020. Descriptive statistics were used to analyse data. Results: Of the 220 service users initiated onto tramadol, almost half (n = 104, 47%) were not contactable. Fifty-eight (26%) people participated, amongst whom most were male (n = 55, 95%). Participants' median age was 32 years. Most participants injected heroin (n = 36, 62.1%). Most participants experienced at least one side effect (n = 47, 81%) with 37 (64%) experiencing two or more side effects from tramadol. Insomnia occurred most frequently (n = 26, 45%). One person without a history of seizures experienced a seizure. Opioid withdrawal symptoms were experienced by 54 participants (93%) whilst taking tramadol. Over half (n = 38, 66%) reported using less heroin whilst on tramadol. Conclusion: Tramadol reduced heroin use but was associated with withdrawal symptoms and unfavourable side effects. Findings point to the limitations of tramadol as opioid withdrawal management to retain people in care and the importance of access to first-line opioid agonists.

Psychosocially-Assisted Pharmacological Treatment of Opioid Dependent Adults: A Systematic Review

Background: Opioid dependence is a conundrum that significantly contributes to global mortality, crimes, and transmission of diseases such as hepatitis (B and C), human immunodeficiency virus and perhaps, coronavirus disease 2019 (COVID-19). There are contradictory findings on the efficacy of psychosocially-assisted pharmacological treatment of opioid dependence in adults. Objective: The overall objective of this research is to investigate if psychosocially-assisted pharmacological therapy has significantly better effect than pharmacological therapy with regards treatment outcomes of opioid dependent adults. Methods: All methods employed in this study are in conformity with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) framework for systematic review which involve identification, screening, eligibility and inclusion. This systematic review involved PubMed literature search on randomized controlled trials published between 1st January 2015 to 1st October 2021. Results: PubMed search yielded 5,216 articles which were screened using inclusion and exclusion criteria resulting in 19 articled being retained for data extraction. Of the 19 articles used in this study, 13 (68.4%) articles having a combined sample size of 1,928 (60.6%) showed that addition of psychosocial intervention to pharmacotherapy significantly improved abstinence from opioid abuse. Conclusion: The outcome of evaluation of the overall evidences presented in the 19 articles used in this study is that psychosocially-assisted pharmacological therapy is significantly better than pharmacological treatment with respect to enhancement of abstinence from opioid abuse among opioid-dependent adults. Additionally, this study has provided specific combinations of psychosocial and pharmacological treatment that can produce significant beneficial effect on opioid abstinence. The huge downturn in randomized controlled trials on treatment of opioid dependence among adults has been highlighted in this study.

Analysis of brain PEBP and ERK in morphine-induced CPP model in rats / 中国药理学通报

Aim To analyze the expression of phosphatidylethanolamine-binding protein(PEBP) and ERK in critical brain regions of psychological dependence rats.Methods Morphine-induced rats conditioned place preference(CPP) model was established to mimic different stages of morphine psychological dependence, during which PEBP expression and ERK activity were assayed in different brain regions.Results PEBP expression in hippocampus, prefrontal cortex, striatum and nucleus accumbens showed no change at three stages of psychological dependence.However, ERK activity increased notably in prefrontal cortex on CPP formation, and decreased remarkably in hippocampus on CPP reinstatement.Conclusions The formation and retrieval of associated memory between morphine effects and environment involve different neural circuits, in which ERK activity is critical, and PEBP might not be involved in such a memory-related ERK regulation.

Changes and the impact on immune function of opioid-dependent subjects by Jitai tabelets during the withdrawal stage / 中华流行病学杂志

Objective To detect the changes in the immune function of opioid-dependent subjects during the withdrawal stage through the administration of Jitai tablet.Methods Subjects were treated as Jitai tablet alone,Jitai tablet plus buprenorphine and placebo,in a randomized,double-blind,placebo-controlled trial.Before and after the 14th day of withdrawal,levels of immunoglobulin (IgM,IgA,IgG),T cell subsets (CD3+,CD4+,CD8+,CD4+/CD8+) and cytokines (IL-2,IFN-γ,IL-4,IFN-γ/IL-4) were detected.Results Compared with healthy people,immunity function before withdrawal among the opioid abusers showed higher levels of IgM,IL-2,IFN-γ,IL-4 and lower level of CD3+ T,as (1.67 ± 0.87) g/L,(14.44 ± 13.50)％,(20.23 ± 15.10)％,(1.97 ± 1.59)％,(47.01 ± 13.62)％,respectively,with difference statistically significant (P＜0.05).There was no big difference of other immunity indicators between the two groups (P＞0.05).At the 14th day of withdrawal in placebo group,levels of IL-4 returned to normal while IFN-γ/IL-4 ratio increased by 3.43 times (P＜0.05).Levels of IgA,IgG,CD4+ and CD4+/CD8+ ratio fluctuated within normal range.There were no significant changes in other immunity indicators (P＞0.05).Compared with placebo group,fluctuation of IgG and IgM decreased in Jitai group during withdrawal period,together with a normal level of IgM at the 14th day.Level of IL-4 abnormally rose up by 0.54 times in Jitai tablet plus buprenorphine group,while IFN-γ/IL-4 ratio been switched back at the 14th day of withdrawal.Other immune indicators were not affected by medical interventions.Conclusion We noticed that certain impairment of the immune function might be restored by Jitai tablet during the withdrawal period.

Changes and the impact on immune function of opioid-dependent subjects by Jitai tabelets during the withdrawal stage / 中华流行病学杂志

Objective To detect the changes in the immune function of opioid-dependent subjects during the withdrawal stage through the administration of Jitai tablet.Methods Subjects were treated as Jitai tablet alone,Jitai tablet plus buprenorphine and placebo,in a randomized,double-blind,placebo-controlled trial.Before and after the 14th day of withdrawal,levels of immunoglobulin (IgM,IgA,IgG),T cell subsets (CD3+,CD4+,CD8+,CD4+/CD8+) and cytokines (IL-2,IFN-γ,IL-4,IFN-γ/IL-4) were detected.Results Compared with healthy people,immunity function before withdrawal among the opioid abusers showed higher levels of IgM,IL-2,IFN-γ,IL-4 and lower level of CD3+ T,as (1.67 ± 0.87) g/L,(14.44 ± 13.50)％,(20.23 ± 15.10)％,(1.97 ± 1.59)％,(47.01 ± 13.62)％,respectively,with difference statistically significant (P＜0.05).There was no big difference of other immunity indicators between the two groups (P＞0.05).At the 14th day of withdrawal in placebo group,levels of IL-4 returned to normal while IFN-γ/IL-4 ratio increased by 3.43 times (P＜0.05).Levels of IgA,IgG,CD4+ and CD4+/CD8+ ratio fluctuated within normal range.There were no significant changes in other immunity indicators (P＞0.05).Compared with placebo group,fluctuation of IgG and IgM decreased in Jitai group during withdrawal period,together with a normal level of IgM at the 14th day.Level of IL-4 abnormally rose up by 0.54 times in Jitai tablet plus buprenorphine group,while IFN-γ/IL-4 ratio been switched back at the 14th day of withdrawal.Other immune indicators were not affected by medical interventions.Conclusion We noticed that certain impairment of the immune function might be restored by Jitai tablet during the withdrawal period.

Effect of different extinction methods on morphine-induced conditioned place preference in mouse / 国际药学研究杂志

Objective To compare the effect of extinction using different methods and the subsequent reinstatement of morphine-primed on morphine-induced conditioned place preference (CPP). Methods Mouse received morphine(10 mg/kg, sc) or saline (10 mg/kg, sc) injections alternately for 8 days to establish CPP. Different methods were used for extinction. Program 1, withdrawal group. Extinction sessions were conducted 21 days after the CPP test at 7 days interval; Program 2, extinction test group. Extinction sessions were carried out once a day from the second day after the CPP test; Program 3, extinction training group. Extinction sessions began one day after the CPP test. Mice were treated alternately two trials daily, in compartments where they received saline instead of morphine. A test for reinstatement was performed on the 2nd or 7th day after all groups completed extinction by 5 mg/kg morphine-primed. Results Morphine injections induce strong CPP. In withdrawal group, CPP extinguished on the 35th day and maintained for at least 28 days. Six trials extinction tests and 4 trials extinction training caused morphine induced CPP extinction. The three programs mentioned above were all primed by 5mg/kg morphine. Conclusion Morphine induced mouse CPP model can maintain at least 28 days, both extinction test and training can accelerate the extinction of CPP, and reinstatement by 5 mg/kg morphine.

Effect of different extinction methods on morphine-induced conditioned place preference in mouse / 国际药学研究杂志

Objective To compare the effect of extinction using different methods and the subsequent reinstatement of morphine-primed on morphine-induced conditioned place preference (CPP).

Research progress on NM23A (expressed in non-metastatic cells) protein / 中国药理学通报

NM23A protein is a kind of multifunctional protein distributed widely in the nature and it exists in almost all the or-ganism and cells. Apart from owning the nucleoside diphosphate kinase activity, NM23A also participates in the physiological process of signal transduction, gene regulation, cell growth and development and so on. NM23A plays important roles in the pa-thology process of the tumor development and metastasis and cen-tral nerve system disease.

Burden of care and quality of life (QOL) in opioid and alcohol abusing subjects.

Background: Alcohol misuse is a major cause of morbidity and mortality and an important health care burden, the Quality of Life (QoL) of alcohol abusing subjects has been little studied to date. Aims & Objective: To assess the burden of care and quality of life of alcohol and opioid dependent subjects. Material and Methods: A cross sectional hospital based study was done. The sample consisted of 37 patients of mixed sex and their family members. The subjects were examined using a semi structured socio demographic profile performa, the WHOQOL-BREF quality of life assessment, Family Burden Interview Schedule (FBIS). Results: The overall mean scores for WHOQOL-Bref were not statistically significant between the alcohol (p=0.93) and the opioid (p=0.99) dependent groups and also the individual domains showed no significant difference between groups. Conclusion: Our study was conducted to analyse the quality of life and burden of care in alcohol and opioid dependent patients. The report of many subjects of poor quality of life during early withdrawal periods stresses the need for implementing ways of improving quality of life during this stage, to reduce relapse, and have better compliance of the detoxification and management measures. Our study also shows that the quality of life of alcohol users is equally poor when compared to that of opioid dependent subjects.

Amnesia and Pain Relief after Cardiopulmonary Resuscitation in a Cancer Pain Patient: A Case Report

The mechanism of chronic pain is very complicated. Memory, pain, and opioid dependence appear to share common mechanism, including synaptic plasticity, and anatomical structures. A 48-yr-old woman with severe pain caused by bone metastasis of breast cancer received epidural block. After local anesthetics were injected, she had a seizure and then went into cardiac arrest. Following cardiopulmonary resuscitation, her cardiac rhythm returned to normal, but her memory had disappeared. Also, her excruciating pain and opioid dependence had disappeared. This complication, although uncommon, gives us a lot to think about a role of memory for chronic pain and opioid dependence.

A Study of Psychiatric Comorbidity in Opioid Dependence.

Aim: To assess psychiatric comorbidity in patients of opioid dependence Method: All the patients of opioid dependence attending alcohol and drug deaddiction OPD and adult psychiatry OPD on specific days, were screened. Those fulfilling the selection criteria were included in the study. A detailed evaluation was done for socio-demographic variables and history of drug using semi-structured proforma especially prepared for the study. Diagnosis of opioid dependence was made according to DSM-IV-TR criteria. The patients were seen for co-morbid psychiatric illness by applying Structured Clinical Interview for DSM-IV-TR I & II (SCID I & II). Results: Out of 25 patients 19 (76.0) were found to have comorbid psychiatric illness. Axis I and Axis II comorbidity was found in 76% and 20% of the samples, respectively. Patients of cluster B personality were dominating in the sample. Patients with more than one comorbidity accounted for 60% of the sample. Conclusion: Psychiatric comorbidity in opioid dependence are very high, other substance in particular. Number of comorbid diagnoses in a person may as high as four.

Progress in agmatine inhibiting opioid dependence / 国际药学研究杂志

Opioid addiction, also termed opioid dependence, is a chronic, relapsing disorder in brain, which induces a series of severe problems in the aspects of society, economy and public health. Because the neurobiological mechanisms of opioid dependence haven't been clarified, it lacks effective medical interventions. Researches on opioid dependence are focusing on clarifying its neurobiological mechanisms and discovering effective anti-relapse drugs. Agmatine is a candidate for neurotransmitter or neuromodulator, and considered as an endogenous ligand for imidazoline receptors. Based on our previous work, its pharmacological characteristics and possible mechanisms of agmatine inhibiting opioid dependence were reviewed.

The first methadone programme in Malaysia: overcoming obstacles and achieving the impossible

Objectives: To determine the best possible programme that suits our local setting, to determine the average dose required, and to determine possible problems that can arise from implementing such a programme locally and how best to address them. Methods: The inclusion criteria were those above 18, a positive urine test, the presence of a supportive carer and willing to engage in the programme. Methadone was initiated and observations relating to dose, adverse events, relationship with carers, work performance, crime and high risk behaviours were monitored for 18 weeks. Results: Two thirds of the 45 subjects completed the trial over the 18 week period. No significant adverse events occurred and improvement in relationship with carers and work performance were noted with reduction in crime and high risk behaviours. Conclusion: Methadone is a safe and effective drug that can be used in the local Malaysian setting.

Cross-talk and molecular mechanisms between NMDA receptor and opioid receptor in opioid dependence / 中国药理学通报

Opioid dependence is based on compensatory adaptations in neurons following chronic exposure to opioids. Recent researches show antagonists of N methyl D aspartate (NMDA) receptors inhibit physical and psychic dependence on opioids. This review focuses on the interactions between opioid receptor system and NMDA receptor system, and on the molecular mechanisms of NMDA receptor contributing to opioid dependence. The clinical prospects of NMDA receptor antagonists and related substances on preventing and treating opioid dependence are aslo discussed.