Do the lockdown-imposed changes in a wastewater treatment plant catchment's socio-demographics impact longitudinal temporal trends in psychoactive pharmaceutical use?

Wastewater-based epidemiology (WBE) includes the analysis of human metabolic biomarkers of xenobiotics in influent wastewater. WBE complements existing drug utilization approaches and provides objective, spatio-temporal information on the consumption of pharmaceuticals in the general population. This approach was applied to 24-h composite influent wastewater samples from Leuven, Belgium. Daily samples were analysed from September 2019 to December 2019 (n = 76), and on three days of the week (Monday, Wednesday, Saturday) from January 2020 to April 2022 (n = 367). Sample analysis consisted of 96-well solid-phase extraction and liquid chromatography coupled to tandem mass spectrometry. Measured concentrations of 21 biomarkers for antidepressant and opioid use were converted to population-normalized mass loads (PNML) by considering the flow rate and catchment population. To capture population movements, mobile phone data was used. Amitriptyline, hydroxy-bupropion, norcitalopram, citalopram, normirtazapine, trazodone, O-desmethylvenlafaxine, codeine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), methadone, morphine, O-desmethyltramadol, and tramadol were included in the temporal assessment since concentrations were above the lower limit of quantification. The PNML of most biomarkers increased (with 3-119 %) throughout the sampling period. The population disruption during the COVID-19 pandemic led to a major change in the socio-demographics of the catchment area, resulting in temporal differences in the PNML of the different biomarkers. As such, higher PNML were observed during the different lockdown phases, which were characterized by the outflow of university students and a decreasing commuting in and out the catchment area. The effects of the fluctuating socio-demographics of the catchment population were further evidenced by the different week-weekend pattern of PNMLs over the course of the sampling campaign. Mean parent/metabolite ratios (i.e., citalopram/norcitalopram, tramadol/O-desmethyltramadol, venlafaxine/O-desmethylvenlafaxine, and methadone/EDDP) remained relatively stable throughout the entire sampling campaign (RSD% below 25 % for all ratios, except for methadone/EDDP) and therefore were not affected by this population change.

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.Contribution: This research contributes to the limited data around short-acting tramadol for opioid withdrawal management in the African context, with specific focus on the need for increased access to opioid agonists for those who need them, in primary care settings.

Impact of COVID-19 on the characteristics of opioid overdose deaths in Arkansas.

BACKGROUND: In the US, spikes in drug overdose deaths overlapping with the COVID-19 pandemic create concern that persons who use drugs are especially vulnerable. This study aimed to compare the trends in opioid overdose deaths and characterize opioid overdose deaths by drug subtype and person characteristics pre-COVID (2017-2019) and one-year post-COVID-19 emergence (2020). METHODS: We obtained death certificates on drug overdose deaths in Arkansas from January 1, 2017, through December 31, 2020. Our analyses consisted of an interrupted time-series and segmented regression analysis to assess the impact of COVID-19 on the number of opioid overdose deaths. RESULTS: The proportion of opioid overdose deaths increased by 36% post-COVID emergence (95% CI: 14%, 59%). The trend in overdose deaths involving synthetic narcotics other than methadone, such as fentanyl and tramadol, has increased since 2018 (74 in 2018 vs 79 in 2019; p=0.02 and 79 in 2019 versus 158 in 2020; p = 0.03). Opioid overdose deaths involving methamphetamine have more than doubled (36 in 2019 vs 82 in 2020; p = 0.06) despite remaining steady from 2018 to 2019. Synthetic narcotics have surpassed methamphetamine (71% vs. 37%) as the leading cause of opioid overdose deaths in Arkansas during the pandemic. This study found that synthetic narcotics are the significant drivers of the increase in opioid overdose deaths in Arkansas during the pandemic. CONCLUSIONS: The co-occurrence of the COVID-19 pandemic and the drug abuse epidemic further highlights the increased need for expanding awareness and availability of resources for treating substance use disorders.

The plausible mechanisms of tramadol for treatment of COVID-19.

Currently, no single medication has been approved for the management of coronavirus disease-2019 (COVID-19) caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, drug repositioningby investigating the use of existing drugs for management of COVID-19 patients is considered a desperate need. Tramadol is a commonly prescribed analgesic drug for treatment of moderate to severe pain with less potential for dependence and respiratory depression. Multiple evidence support that tramadol is a promising drug for treatment of COVID-19 patients. Herein, we discuss the possible beneficial effects of using tramadol against SARS-CoV-2 infection and their underlying mechanism of action. The anti-inflammatory effect of tramadol may help to suppress the COVID-19 related cytokine storm through decreasing interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP). Besides, tramadol activates natural killer (NK) and T-cells and enhances IL-2 secretion, which produce immune-enhancing effect against SARS-CoV-2. Recent studies confirmed that COVID-19 patients with acute respiratory failure showed increased fibrin formation and polymerization that may lead to thrombosis. Tramadol owing to its hypocoagulable effect may protect against venous thromboembolism in these patients. Moreover, tramadol can exert a cardioprotective effect via decreasing lactate dehydrogenase (LDH) level which is elevated in most of patients with COVID-19. Furthermore, the severity and mortality of COVID-19 have been correlated with old age patients, which may be due to the lack of antioxidant mechanisms and increased oxidative damage. Tramadol could protect COVID-19 patient from disease complications by increases the antioxidant enzymes superoxide dismutase and glutathione peroxidase while diminished malondialdehyde. More interestingly, tramadol as an effective analgesic and antitussive may have a beneficial effect on COVID-19 patients suffering from cough, headache, ache, and pain. The tramadol anti-psychotic effect may also protect against psychiatric disorders associated with SARS-CoV-2 infection. Moreover, tramadol has bactericidal activity against a wide range of pathogens including Pseudomonas aeruginosa which is common in severe COVID-19 patients leading to pneumonia with worse clinical outcomes. Therefore, we hypothesize that tramadol might be a promising adjuvant therapeutic option against SARS-CoV-2 infection. Based on that, tramadol should be considered as adjuvant therapy for COVID-19 clinical trials.