Naloxone

ImportanceThe US Food and Drug Administration approved Narcan, a nasal spray formulation of naloxone, for sale as an over-the-counter (OTC) medication in March 2023. The purpose of OTC approval was to improve naloxone accessibility to reduce opioid overdoses; however, research has not yet evaluated whether naloxone's availability and cost changed since this policy was implemented.ObjectiveTo evaluate whether the accessibility and cost of naloxone at North Carolina community pharmacies changed after OTC naloxone became available and whether cost and availability varied by pharmacy type and urbanicity.Design, setting, and participantsThis longitudinal telephone-based secret shopper survey study included a stratified sample of 202 North Carolina community pharmacies, including health department, independent, and chain pharmacies. There were 2 separate data collection efforts from March to April 2023 (before OTC naloxone could be sold at pharmacies) and November 2023 to January 2024 (after OTC naloxone was sold at pharmacies).ExposureOTC naloxone first became available for sale at community pharmacies in September 2023.Main outcomes and measuresThe main outcomes were same-day availability of naloxone without a clinician-issued prescription and the quoted out-of-pocket cost for cash-paying patients.ResultsData were collected from 192 pharmacies. Same-day naloxone availability increased from 42.2% (81 of 192) before OTC naloxone availability to 57.8% (111 of 192) after (P Conclusions and relevanceThe Food and Drug Administration's approval of OTC naloxone nasal spray contributed to an increase in pharmacy-based availability of naloxone and a reduction of its cost for cash-paying patients. Cost was higher at independent pharmacies compared with chain pharmacies and lower in urban pharmacies compared with suburban and rural pharmacies.

We investigated the potential role of the opioid system in modulating glutamatergic effects of ketamine administration in major depressive disorder. Twenty-six adults with major depressive disorder participated in a double-blind crossover study, receiving oral placebo or 50 mg naltrexone before an intravenous infusion of 0.5 mg per kg ketamine. Brain glutamatergic activity in the anterior cingulate cortex was measured using functional magnetic resonance spectroscopy and depressive symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale. Naltrexone attenuated the increase in glutamate + glutamine to total N-acetylaspartate ratio during ketamine infusion compared to placebo (F1,253 = 4.83, P = 0.029) and also attenuated the reduction in Montgomery-Åsberg Depression Rating Scale scores on day 1 (condition-by-time interaction, F1,74 = 5.39, P = 0.023). These findings demonstrate that the opioid system modulates the acute response to ketamine and subsequent antidepressant effects. Interactions between the glutamate and opioid systems may have implications for the development of new depression treatment strategies. ClinicalTrials.gov registration: NCT04977674 .

BackgroundIt is estimated that over 111,000 people in the U.S. died from a drug overdose in the twelve-month period ending in July 2023. More than three-quarters of those deaths were attributed to opioids. Naloxone has long been available in healthcare facilities to reverse opioid overdose rapidly and safely but is not universally accessible for use in community settings where overdoses occur. We conducted a systematic literature review and meta-analysis to assess the effectiveness of overdose education and naloxone distribution (OEND) programs in three types of community settings to reduce overdose deaths among people who use opioids nonmedically.MethodsWe systematically searched electronic databases, including Medline (OVID), Embase (OVID), Psycinfo (OVID), and Global Health (OVID), for peer-reviewed studies of OEND programs published during 2003-2018 (Group 1) that reported overdose outcomes individual level survivals or deaths immediately following naloxone administration. The PRISMA checklist guided screening, quality assessment, and data abstraction. We later identified studies published during 2018-2022 (Group 2), when drug usage and fentanyl-related overdose deaths notably increased, differed from earlier ones. We conducted meta-analyses on both Groups using random effects models to estimate summary survival proportions.ResultsAmong the 44 Group 1 studies published during 2003-2018, survival did not differ by time (year), location, naloxone dose, or route of administration, but studies of OEND programs serving people who use drugs reported 98.3% (95% CI: 97.5-98.8) survival; those serving family of people who use drugs or other community members reported 95.0% (95% CI: 91.4-97.1) survival; and those for police reported 92.4% (95% CI: 88.9-94.8) survival (p ConclusionsCommunity-based naloxone distribution programs can be effective in preventing opioid overdose deaths. The paper demonstrates that in the face of increasing overdose deaths over time, survival after naloxone administration has been sustained. The very high survival rates provide clear evidence for public health to continue efforts to expand channels for naloxone distribution in community settings.

The opioid epidemic continues to claim lives at alarming rates, disproportionately affecting marginalized communities, with structural barriers preventing equitable access to lifesaving interventions such as naloxone. Harm reduction vending machines (HRVMs) offer a promising solution to this issue, providing low-barrier access to naloxone and other harm reduction supplies. This study examines the impact of different HRVM access models on product utilization, specifically focusing on an outdoor HRVM, Project HOPE, located in Bakersfield, California. Initially, the machine required participant registration and imposed product limits; however, these restrictions were removed in August 2023 to improve access. An interrupted time series analysis of data from June to October 2023 reveal a significant increase in product utilization following the shift to unrestricted access, with increases in demand for naloxone kits, safer injection kits, wound care kits, and other basic needs supplies. The findings suggest that removing barriers to HRVM access, including registration requirements and product limits, can significantly improve the utilization of harm reduction supplies, potentially reducing opioid-related fatalities and promoting health equity. Further research is needed to evaluate the long-term impacts of unrestricted HRVM access models on overdose prevention and other health outcomes.