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Non-pharmaceutical fentanyl and its analogs have driven striking increases in opioid-associated overdose deaths. These highly potent opioids can be found at low concentrations in biological specimens. Little is known regarding the concentrations of these substances among survivors of non-fatal overdoses. In a locale where fentanyl is responsible for the majority of non-fatal opioid overdoses, we compared the concentration of fentanyl in blood to naloxone dosing in the presence and absence of a concurrent sedative-hypnotic exposure. In this pilot study, we enrolled adult patients presenting to the emergency department (ED) who: (1) arrived after an overdose requiring naloxone for the reversal of respiratory depression; and (2) who required venipuncture or intravenous access as part of their clinical care. Blood specimens (n = 20) underwent comprehensive toxicology testing, including the quantitation of fentanyl, fentanyl analogs, and naloxone, as well as the detection of common sedative-hypnotics and a wide range of other illicit and pharmaceutical substances. We then compared fentanyl concentrations to naloxone dosing in participants with and without a concomitant sedative-hypnotic exposure. Nineteen of twenty participants (95%) were exposed to fentanyl prior to their overdose; the remaining participant tested positive for heroin metabolites. No participants reported pharmaceutical fentanyl use. Fentanyl analogs ��� acetylfentanyl or carfentanil ��� were present in three specimens. In 11 cases, fentanyl and its metabolites were the only opioids identified. Among the fentanyl-exposed, blood concentrations ranged from

Introduction: Despite widespread recognition of the opioid crisis, opioid overdose remains a common reason for Emergency Department (ED) utilization. Treatment for these patients after stabilization often involves the provision of information for outpatient treatment options. Ideally, an ED visit for overdose would present an opportunity to start treatment for opioid use disorder (OUD) immediately. Although widely recognized as effective, opioid agonist therapy with methadone and buprenorphine commonly referred to as “medication-assisted therapy” but more correctly as “medication for addiction treatment” (MAT), can be difficult to access even for motivated individuals due to shortages of prescribers and treatment programs. Moreover, opioid agonist therapy may not be appropriate for all patients, as many patients who present after overdose are not opioid dependent. More treatment options are required to successfully match patients with diverse needs to an optimal treatment plan in order to avoid relapse. Naltrexone, a long-acting opioid antagonist, available orally and as a monthly extended-release intramuscular injection, may represent another treatment option. Methods: We conducted a literature search of MEDLINE and PubMed. We aimed to capture references related to naltrexone and is use as MAT for OUD, as well as manuscripts that discussed naltrexone in comparison toother agents used for MAT, opioid detoxification, and naltrexone metabolism. Our initial search logic returned a total of 618 articles. Following individual evaluation for relevance, we selected 65 for in-depthreview. Manuscripts meeting criteria were examined for citations meriting further review, leading to the addition of 30 manuscripts Conclusions: Here, we review the pharmacology of naltrexone as it relates to OUD, its history of use, and highlight recent studies and new approaches for use of the drug as MAT including its potential initiation after ED visit for opioid overdose.

1.AbstractMemory formation is crucial for the survival of animals. Here, we study the effect of differentcrh-1(C. eleganshomolog of mammalian CREB1) mutations on the ability ofC. elegansto form long-term memory (LTM). Null mutants increb1/crh-1are defective in LTM formation across phyla. We show that specific isoforms of CREB1/CRH-1, CRH-1c and CRH-1e, are primarily responsible for memory related functions of the transcription factor inC. elegans. Silencing of CRH-1e expressing neurons during training for LTM formation abolishes the long-term memory of the animal. Further, CRH-1e expression in RIM or AVE neurons is sufficient to rescue long-term memory defects ofcreb1/crh-1null mutants. We show that apart from being LTM defective,creb1/crh-1null mutant animals show defects in native chemotaxis behavior. We characterize the amino acids K247 and K266 as responsible for the LTM related functions of CRH-1 while being dispensable for it’s native chemotaxis behavior. These findings provide insight into the spatial and temporal workings of a crucial transcription factor and can be further exploited to find CREB1 targets involved in the process of memory formation.

As part of the mini-symposium entitled "The Problems with Marijuana and Driving: Medical, Legal, and Public Health Perspectives," Dr. Babu describes the state of the science on measurement of marijuana in the context of driving impairment.

Background: Opioid misuse is a known public health problem, nationwide and in Massachusetts. The Massachusetts Hospital Association (MHA) developed recommendations to address opioid prescribing in the ED setting, and UMassMemorial Health Care recently implemented a system-wide opioid practice guideline mirroring the MHA policy. Little is known about methods to influence behavior change among ED providers related to opioid prescribing practices. Guideline implementation provided a unique opportunity for a natural experiment related to prescribing patterns, and we hypothesized that a simultaneous experimental intervention to provide clinicians with their individual prescribing data would alter their practices beyond any effect achieved solely by being subject to the new guidelines. Methods: As part of an ongoing, prospective, randomized trial of an intervention hypothesized to influence providers’ opioid prescribing, we developed a survey instrument consisting of graphical depictions of the distributions of three measures of opioid prescribing among all ED providers at four UMass-affiliated EDs (attending and resident physicians and advanced practice providers). Clinicians randomized to the intervention arm were asked to identify his/her perceived position on each distribution. We compared each provider’s self-perception to their actual decile. Results: Fifty-one providers were randomized to the intervention arm. Forty-eight completed the survey (94%). Providers underestimated their decile of opioid prescriptions per hundred total prescriptions by a median of one decile (p=0.0399 for difference from zero). Attendings underestimated their decile of percentage of patients dispositioned with an opioid prescription by a median of two deciles (p=0.0292), while residents did not exhibit a significant difference. Providers showed systematic disagreement with their raw number of prescriptions for extended-release opioid formulations (kappa -0.18), underestimating by a median of one. Conclusions: Based upon three measures of ED opioid prescribing, providers’ self-perceptions of their practices systematically underestimated their actual prescribing, which likely has implications related to efforts to influence clinician behavior change.