Xylazine potentiates the lethal but not the rewarding effects of fentanyl in mice.

BACKGROUND: Fentanyl is commonly laced with xylazine. People who use this combination report heightened effects, but it also increases death risk. Although no medication has been approved to counteract overdoses produced by fentanyl and xylazine, naloxone is frequently used. This paper studies the preclinical rewarding and lethal effects of fentanyl combined with xylazine and the efficacy of yohimbine or naloxone to prevent death. METHODS: Male Swiss Webster mice were treated with (in mg/kg, i.p.) xylazine (0.3, 1, 3, or 5.6), fentanyl (0.01, 0.3, or 0.1), or 1 xylazine plus 0.01 (non-effective) or 0.1 (effective) fentanyl doses during the conditioned-place preference (CPP) test. In addition, independent groups received (in mg/kg, i.p.): xylazine (31.6, 60, 74.2, or 100), fentanyl (3.1 or 10), or both substances at two doses: 31.6 xylazine + 3.1 fentanyl, or 60 xylazine + 10 fentanyl to analyze lethal effects. We determined whether yohimbine or naloxone (each medication tested at 10 or 30mg/kg) could prevent the lethality produced by fentanyl/xylazine combinations. Female mice were also tested in key experiments. RESULTS: Xylazine neither induced CPP nor altered fentanyl's rewarding effects. In contrast, lethality was potentiated when fentanyl was combined with xylazine. Naloxone, but not yohimbine, effectively prevented the lethality of the fentanyl/xylazine combinations. CONCLUSIONS: At the doses tested, xylazine does not increase the rewarding effect of fentanyl on the CPP in male mice but potentiates the risk of fatal overdose in male and female mice. A high naloxone dose prevents death induced by coadministration of fentanyl and xylazine in both sexes.

Non-Fatal Opioid Overdose and Abuse Visits to a University Hospital Emergency Department in Puerto Rico, 2009-2018.

OBJECTIVE: The objective was to describe opioid-use trends (2009-2018) at a university hospital emergency department (ED) in metropolitan San Juan, Puerto Rico. METHODS: The ED database of the University of Puerto Rico - Dr. Federico Trilla Hospital provided the data for the study. RESULTS: Non-fatal opioid overdoses surged 7.5-fold, increasing from 12.1 (±2.5) per 100,000 ED encounters for 2009 through 2016 to 91.2 (±8.7) per 100,000 ED encounters for 2017 through 2018 (P < .0001). Starting in summer 2017, the surge reached its peak in October after two major hurricanes. The opioid-related ED cases comprised 15.8% from 2009 through 2016, increasing to 67% in 2017 through 2018. Prior to October 2015, multiple drugs were mentioned in 65% of the opioid-related cases, decreasing to 37% of the total cases, thereafter. Cocaine was reported in combination with opioids in 53% of all opioid-related cases from August 2009 through September 2015, decreasing to 21% from October 2015 through December 2018, cannabis in 15 % and 10%, respectively, and alcohol in 10% and 6%, respectively. Amphetamines were mentioned once in combination with opioids. The overall male:female ratio for all opioid-related cases was 6.3 (rate: 8.8). CONCLUSION: The data show an increase in opioid-toxicity cases in the area served by the above-named hospital beginning in mid-2017. Opioid-related cases overwhelmingly involved male patients. More work is needed to establish islandwide trends.

Barriers to and recommendations for take-home naloxone distribution: perspectives from opioid treatment programs in New Mexico.

BACKGROUND: Naloxone is a safe and effective medication to help reverse opioid overdose. Providing take-home naloxone to patients in opioid treatment settings is a critical step to reducing opioid overdose deaths. In New Mexico, a US state with one of the highest rates of opioid overdose deaths, legislation was passed in 2017 (House Bill 370) to support take-home naloxone, and followed by naloxone training of Opioid Treatment Program staff to increase distribution. METHODS: Naloxone training was offered to all New Mexico Opioid Treatment Programs along with a baseline survey to assess current practices and barriers to take-home naloxone distribution. Focus groups were conducted approximately 1 year post-training with staff at a subset of the trained Opioid Treatment Programs to assess the impact of the legislation and training provided. RESULTS: Baseline survey results show most Opioid Treatment Program staff were unfamiliar with House Bill 370, reported conflicting understandings of their agency's current take-home naloxone practices, and reported a number of barriers at the patient, agency, and policy level. Follow-up focus groups revealed support for House Bill 370 but persistent barriers to its implementation at the patient, agency, and policy level including patient receptivity, cost of naloxone, staff time, and prohibitive pharmacy board regulations. CONCLUSIONS: In spite of targeted legislation and training, provision of take-home naloxone at remained low. This is alarming given the need for this lifesaving medication among the Opioid Treatment Program patient population, and high opioid death rate in New Mexico. Locally, important next steps include clarifying regulatory guidelines and supporting policy/billing changes to offset costs to Opioid Treatment Programs. Globally, additional research is needed to identify the prevalence of take-home naloxone distribution in similar settings, common barriers, and best practices that can be shared to increase access to this vital lifesaving medication in this critical context.