Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial

The increasing prevalence of illicit stimulant use among those in opioid treatment programs poses a significant risk to public health, stimulant users have the lowest rate of retention and poorest outcomes among those in addiction treatment, and current treatment options are limited. Oxytocin administration has shown promise in reducing addiction-related behavior and enhancing salience to social cues. We conducted a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin administered twice daily for 6 weeks to male Veterans with stimulant use disorder who were also receiving opioid agonist therapy and counseling (n = 42). There was no significant effect of oxytocin on stimulant use, stimulant craving, or therapeutic alliance over 6 weeks. However, participants receiving oxytocin (vs. placebo) attended significantly more daily opioid agonist therapy dispensing visits. This replicated previous work suggesting that oxytocin may enhance treatment engagement among individuals with stimulant and opioid use disorders, which would address a significant barrier to effective care.

Measuring Treatment Attrition at Various Stages of Engagement in Opioid Agonist Treatment in Ontario Canada Using a Cascade of Care Framework

Background The cascade of care framework is an effective way to measure attrition at various stages of engagement in Opioid Agonist Treatment (OAT). The primary objective of the study was to describe the cascade of care for individuals who have accessed OAT from a network of specialized addiction clinics in Ontario, Canada. The secondary objectives were to evaluate correlates associated with retention in OAT at various stages and the impact of patients' location of the residence on retention in OAT. Design: A multi-clinic retrospective cohort study was conducted using electronic medical record (EMR) data from the largest network of OAT clinics in Canada (70 clinics) from 2014-2020. Study participants included all individuals who received OAT from the network of clinics during the study period. Measurements: In this study, four stages of the cascade of care framework were operationalized to identify treatment engagement patterns, including patients retained within 90 days, 90 to 365 days, one to two years, and more than two years. Correlates associated with OAT retention for 90 days, 90 to 365 days, one to two years, and more than two years were also evaluated and compared across rural and urban areas in northern and southern Ontario. Results A total of 32,487 individuals were included in the study. Compared to individuals who were retained in OAT for 90 days, individuals who were retained for 90 to 365 days, one to two years, or more than two years were more likely to have a higher number of treatment attempts, a higher number of average monthly urine drug screening and a lower proportion of positive urine drug screening results for other drug use. Conclusion Distinct sociodemographic and clinical factors are likely to influence treatment retention at various stages of engagement along the OAT continuum. Research is required to determine if tailored strategies specific to people at different stages of engagement have the potential to improve outcomes of OAT.

Bifunctional Opioid/Melanocortin Peptidomimetics for Use in Neuropathic Pain: Variation in the Type and Length of the Linker Connecting the Two Pharmacophores

Based on the mechanism of neuropathic pain induction, a new type of bifunctional hybrid peptidomimetics was obtained for potential use in this type of pain. Hybrids consist of two types of pharmacophores that are connected by different types of linkers. The first pharmacophore is an opioid agonist, and the second pharmacophore is an antagonist of the pronociceptive system, i.e., an antagonist of the melanocortin-4 receptor. The results of tests in acute and neuropathic pain models of the obtained compounds have shown that the type of linker used to connect pharmacophores had an effect on antinociceptive activity. Peptidomimetics containing longer flexible linkers were very effective at low doses in the neuropathic pain model. To elucidate the effect of linker lengths, two hybrids showing very high activity and two hybrids with lower activity were further tested for affinity for opioid (mu, delta) and melanocortin-4 receptors. Their complexes with the target receptors were also studied by molecular modelling. Our results do not show a simple relationship between linker length and affinity for particular receptor types but suggest that activity in neuropathic pain is related to a proper balance of receptor affinity rather than maximum binding to any or all of the target receptors.

Oliceridine as a Novel Selective mu-receptor G-protein Pathway Modulator: A Narrative review

Objective: To review the literature on equianalgesic efficacy and better safety(less respiratory depression and gastrointestinal dysfunction) of oliceridine versus opioid analgesic in moderate to severe postoperative pain. Methodology: A comprehensive literature search was conducted in PubMed (January 2021 to March 2021) using keywords as ‘oliceridine’, ‘ligand biased mu receptor agonist’, ‘acute postoperative pain’, ‘conventional opioids’ and ‘morphine’. All English language full text pre-clinical and clinical research articles were searched. In addition, other data source was from ClinicalTrial. Gov. Data Synthesis: Oliceridine is a novel selective µ (mu)-receptor G-protein pathway modulator. G protein biased mu receptor agonists are a new class of opioids exhibiting analgesic properties at par to morphine with less respiratory depressant properties. Oliceridine a first-in-class intravenous (IV) analgesic has received the US FDA approval in August 2020, for management of moderate to severe acute pain in adults. The drug can be administered in cases where the pain is severe enough to require an intravenous opioid and when alternative treatments become inadequate. Oliceridine is an opioid agonist with a rapid onset of action within two to five minutes, was administered via clinician-administered bolus dosing, patient-controlled analgesia (PCA), or a combination of the two. Bolus dosing was initiated at 1 to 2 mg, with supplemental doses of 1 to 3 mg every one to three hours, as needed, based on individual patient need and previous response to oliceridine in management of acute post-operative pain. If oliceridine was administered via PCA, the loading dose was 1.5 mg, the demand dose was 0.5 mg, and the lockout interval (repeat dose)was six minutes. The clinically relevant concentration range of 0 to 35 ng/ml. It is indicated for short-term use only & limited to hospitals or other controlled clinical settings. Oliceridine requires no dosage adjustments in patients with renal impairment as well as in patient with significant medical complications. Therefore, opioids that bias towards G-protein and away from β arrestin signaling should produce analgesia with reduced side effects.