The effects of pioglitazone, a PPARγ receptor agonist, on the abuse liability of oxycodone among nondependent opioid users

Aims: Activation of PPARγ by pioglitazone (PIO) has shown some efficacy in attenuating addictive-like responses in laboratory animals. The ability of PIO to alter the effects of opioids in humans has not been characterized in a controlled laboratory setting. The proposed investigation sought to examine the effects of PIO on the subjective, analgesic, physiological and cognitive effects of oxycodone (OXY). Methods: During this investigation, nondependent prescription opioid abusers (N = 17 completers) were maintained for 2-3 weeks on ascending daily doses of PIO (0 mg, 15 mg, 45 mg) prior to completing a laboratory session assessing the aforementioned effects of OXY [using a within-session cumulative dosing procedure (0, 10, and 20 mg, cumulative dose = 30 mg)]. Results: OXY produced typical mu opioid agonist effects: miosis, decreased pain perception, and decreased respiratory rate. OXY also produced dose-dependent increases in positive subjective responses. Yet, ratings such as: drug "liking," "high," and "good drug effect," were not significantly altered as a function of PIO maintenance dose. Discussion: These data suggest that PIO may not be useful for reducing the abuse liability of OXY. These data were obtained with a sample of nondependent opioid users and therefore may not be applicable to dependent populations or to other opioids. Although PIO failed to alter the abuse liability of OXY, the interaction between glia and opioid receptors is not well understood so the possibility remains that medications that interact with glia in other ways may show more promise

Multi-informant Implementation and Intervention Outcomes of Opioid Overdose Education and Naloxone Distribution in New York City

Overdose Education and Naloxone Distribution (OEND) is an effective public health intervention to reduce opioid overdose fatalities (McDonald and Strang, Addiction 111:1177–1187, 2016). However, we know little about OEND implementation outcomes (i.e., indicators of implementation success), specifically the fidelity of training delivery, and how these may relate to intervention outcomes (i.e., indicators of the success or effectiveness of an intervention), such as overdose knowledge and attitudes. This study evaluated 16 OEND trainings conducted at different Opioid Overdose Prevention Programs in New York City. Trainees (N = 75) completed the Opioid Overdose Knowledge and Attitude Scales before and after training (intervention outcomes). Implementation outcomes were fidelity (competence and adherence of the trainer, N = 10; modified Fidelity Checklist) and acceptability of OEND (Acceptability of Intervention Measure), assessed from multiple perspectives (trainees, trainers, and an independent observer). Trainees’ overdose knowledge, t(71) = − 8.12, p < 0.001, 95% CI [− 6.54, − 3.96], and attitudes, t(65) = − 6.85, p < 0.001, 95% CI [− 0.59, − 0.33], improved significantly from pre- to post-training. Stepwise multiple regression models indicated that adherence of the trainer rated from the observer perspective added significantly to the prediction of changes in overdose knowledge, F(1, 67) = 9.81, p = 0.003, and explained 13% of the variance in outcome. However, fidelity measures from the perspective of trainees or trainers and acceptability of OEND were not associated with changes in trainees’ overdose knowledge or attitudes. OEND implementation outcomes and their relationship with intervention outcomes differed depending on the role of the fidelity rater in relation to the intervention. Specifically, our findings indicate that fidelity should be measured from an independent perspective (i.e., an individual who is experienced with fidelity rating but not directly involved in the intervention)

Opioid overdose reversals using naloxone in New York City by people who use opioids:Implications for public health and overdose harm reduction approaches from a qualitative study

BACKGROUND: Adverse reactions to naloxone, such as withdrawal symptoms and aggression, are widely recognised in the literature by pharmaceutical manufacturers and clinical practitioners as standard reactions of individuals who are physically dependent upon opioid drugs following the reversal of potentially fatal opioid overdose. This paper seeks to provide a differentiated view on reactions to naloxone that may have important implications for public health and harm reduction approaches. METHODS: Analyses from a qualitative investigation embedded within a 5-year Randomized Controlled Trial (RCT) examined the risks and benefits of Overdose Education and Naloxone Distribution (OEND) training models (brief or extended training) in various populations of people who use opioids in New York City. The qualitative experiences (obtained through semi-structured interviews) of 46 people who use opioids and who were each involved in the delivery of naloxone, during 56 separate overdose events that occurred throughout 2016–2018, were studied. Situational analysis and inductive content analysis of interview data focused upon overdose reversals in an attempt to provide understandings of the various adverse effects associated with naloxone from their perspective. These analyses were supplemented by data sessions within the research team during which the findings obtained from situational analysis and inductive content analysis were reviewed and complemented by deductive (clinical) appraisals of the various physical and psychological effects associated with the overdose reversals. RESULTS: People who use opioids recognise three distinct and interconnected outcomes that may follow a successful opioid overdose reversal after intramuscular or intranasal administration of naloxone. These outcomes are here termed, i) ‘rage’ (describing a wide range of angry, hostile and/or aggressive outbursts), ii) ‘withdrawal symptoms,’ and iii) ‘not rage, not withdrawal’ (i.e., a wide range of short-lived, ‘harmless’ conditions (such as temporary amnesia, mild emotional outbursts, or physical discomfort) that do not include rage or withdrawal symptoms). CONCLUSION: Physical and psychological reactions to naloxone should not be understood exclusively as a consequence of acute, opioid-related, withdrawal symptoms. The three distinct and interconnected reversal outcomes identified in this study are considered from a harm reduction policy perspective and are further framed by concepts associated with ‘mediated toxicity’ (i.e. harm triggered by medicine). The overall conclusion is that harm reduction training programmes that are aligned to the policy and practice of take home naloxone may be strengthened by including awareness and training in how to best respond to ‘rage’ associated with overdose reversal following naloxone administration by people who use opioids and other laypersons

A qualitative study of repeat naloxone administrations during opioid overdose intervention by people who use opioids in New York City.

BACKGROUND: Take-home naloxone (THN) kits have been designed to provide community members (including people who use drugs, their families and/or significant others) with the necessary resources to address out-of-hospital opioid overdose events. Kits typically include two doses of naloxone. This 'twin-pack' format means that lay responders need information on how to use each dose. Advice given tends to be based on dosage algorithms used by medical personnel. However, little is currently known about how and why people who use drugs, acting as lay responders, decide to administer the second dose contained within single THN kits. The aim of this article is to explore this issue. METHODS: Data were generated from a qualitative semi-structured interview study that was embedded within a randomised controlled trial examining the risks and benefits of Overdose Education and Naloxone Distribution (OEND) training in New York City (NYC). Analysis for this article focuses upon the experiences of 22 people who use(d) opioids and who provided repeat naloxone administrations (RNA) during 24 separate overdose events. The framework method of analysis was used to compare the time participants believed had passed between each naloxone dose administered (‘subjective response interval’) with the ‘recommended response interval’ (2-4 minutes) given during OEND training. Framework analysis also charted the various reasons and rationale for providing RNA during overdose interventions. RESULTS: When participants’ subjective response intervals were compared with the recommended response interval for naloxone dosing, three different time periods were reported for the 24 overdose events: i. ‘two doses administered in under 2 minutes’ (n=10); ii. ‘two doses administered within 2-4 minutes’ (n=7), and iii. ‘two doses administered more than 4 minutes apart’ (n=7). A variety of reasons were identified for providing RNA within each of the three categories of response interval. Collectively, reasons for RNA included panic, recognition of urgency, delays in retrieving naloxone kit, perceptions of recipients’ responsiveness/non-responsiveness to naloxone, and avoidance of Emergency Response Teams (ERT). CONCLUSION: Findings suggest that decision-making processes by people who use opioids regarding how and when to provide RNA are influenced by factors that relate to the emergency event. In addition, the majority of RNA (17/24) occurred outside of the recommended response interval taught during OEND training. These findings are discussed in terms of evidence-based intervention and ‘evidence-making intervention’ with suggestions for how RNA guidance may be developed and included within future/existing models of OEND training