Hydromorphone

Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes.

BackgroundThe use of opioid analgesics for patients with chronic nonmalignant pain is becoming more widely accepted, and long-acting formulations are an important treatment option.AimTo assess conversion to extended-release OROS hydromorphone from previous stable opioid agonist therapy in patients with chronic nonmalignant pain of moderate-to-severe intensity.MethodsIn this open-label multicentre trial, patients were stabilised on their previous opioid therapy before being switched to OROS hydromorphone at a ratio of 5 : 1 (morphine sulphate equivalent to hydromorphone hydrochloride). The OROS hydromorphone dose was titrated over 3-16 days to achieve effective analgesia, and maintenance treatment continued for 14 days.ResultsStudy medication was received by 336 patients; 66% completed all study phases. Stabilisation of OROS hydromorphone was achieved by 94.6% of patients, the majority in two or fewer titration steps (mean time, 4.2 days). Mean pain intensity scores, as determined by the Brief Pain Inventory, decreased during OROS hydromorphone treatment (p ConclusionPatients with chronic nonmalignant pain who had been receiving opioid therapy easily underwent conversion to OROS hydromorphone, with no loss of efficacy or increase in adverse events.

BackgroundThe North American Opiate Medication Initiative (NAOMI) clinical trial compared the effectiveness of injectable diacetylmorphine (DAM) or hydromorphone (HDM) to oral methadone maintenance treatment (MMT). This study aimed to determine participants' perceptions of treatment delivered in NAOMI.MethodsA qualitative sub-study was conducted with 29 participants (12 female): 18 (62.1%) received injectable DAM or HDM and 11 (37.9%) received MMT. A phenomenological theoretical framework was used. Semi-structured interviews were audio-recorded and transcribed verbatim. A thematic analysis was used over successive phases and was driven by the semantic meanings of the data.ResultsParticipants receiving injectable medications suggested that the supervised delivery model was stringent but provided valuable stability to their lives. Females discussed the adjustment required for the clinical setting, while males focused on the challenging clinic schedule and its impact on employment abilities. Participants receiving MMT described disappointment with being randomized to this treatment; however, positive aspects, including the quick titration time and availability of auxiliary services, were also discussed.ConclusionTreatment with injectable DAM (or HDM) is preferred by participants and considered effective in reducing the burden of opioid dependency. Engaging patients in research regarding their perceptions of treatment provides a comprehensive assessment of treatment needs and barriers.Clinical trial registrationNCT00175357.

SettingThe crisis of unregulated fentanyl-related overdose deaths presents a significant public health challenge. This article describes the implementation and evaluation of four Safer Opioid Supply programs (SSPs) in Ontario, one in London and three in Toronto.Intervention and implementationSSPs aim to curtail overdose fatalities while connecting individuals using drugs to healthcare services. The programs involve a daily dispensed prescription of immediate-release hydromorphone tablets for take-home dosing alongside an observed dose of long-acting opioids like slow-release oral morphine. Implemented within a multidisciplinary primary care framework, these programs emphasize patient-centred approaches and comprehensive health and social support.OutcomesIn our study conducted in 2020/2021, clients and service providers reported that receiving pharmaceutical opioids through these programs improved the clients' health and well-being. The regulated supply was reported to lead to decreases in overdose incidents, use of unregulated substances, and criminalized activities. Increased engagement with healthcare and harm reduction services and improvements in social determinants of health, such as food security, were also reported. Despite these positive outcomes, some implementation challenges, including capacity issues and provider burnout, were described by service providers.ImplicationsOur findings suggest that the combination of safer supply, wrap-around support, and harm reduction within primary care settings can lead to increased healthcare engagement, HIV/HCV prevention, testing, and treatment uptake, reducing the burden of infectious diseases and overdose risk. SSPs have the potential to meaningfully reduce overdose rates, address the ongoing overdose crisis, and if scaled up, influence population-level outcomes.