Novel Opioid

PURPOSE OF REVIEW: Opioid use disorder (OUD) presents a serious public health concern, with dramatic increases in opioid-overdose mortality in recent years and a small percentage of those with OUD accessing or remaining engaged with available treatments. Efforts are currently underway to identify and vaccines targeting opioids, which could provide a novel and complimentary approach. The current review provides an overview of existing literature, practical considerations for designing and conducting clinical trials with vaccines for opioids, and future directions...

BACKGROUND: Postoperative pain management is crucial for improving patient outcomes following posterior cervical spine surgery. Opioids are effective but carry a risk of respiratory depression. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used but may not provide adequate pain relief and have potential complications. The inter-semispinalis plane (ISPB) block is a novel technique for postoperative analgesia in cervical spine surgery. OBJECTIVES: This study aims to evaluate and compare the efficacy of the ISPB with general anesthesia in terms of analgesia, postoperative Visual Analog Scale (VAS) pain scores, patient-surgeon satisfaction levels, and the occurrence of postoperative complications...

OBJECTIVE: This study aimed to explore and identify motivational factors and barriers for pharmacy personnel participation in specific opioid mitigation programs, using the Theory of Planned Behavior (TPB) as an investigational framework. METHODS: A naturalistic inquiry method was employed involving semi-structured interviews with pharmacy personnel to assess their intentions, attitudes, normative beliefs, and behaviors towards participating in naloxone dispensing and provision of at-home drug disposal solutions...

BACKGROUND: Opioid and substance misuse has become a widespread problem in the United States, leading to the "opioid crisis." The relationship between substance misuse and mental health has been extensively studied, with one possible relationship being that substance misuse causes poor mental health. However, the lack of evidence on the relationship has resulted in opioids being largely inaccessible through legal means. OBJECTIVES: This study aims to analyze social media posts related to substance use and opioids being sold through cryptomarket listings...

The increased prevalence of opioid use disorder (OUD) has made it imperative to disentangle the biological mechanisms contributing to individual differences in susceptibility to OUD. OUD shows strong heritability, however genetic variants contributing toward vulnerability remain poorly defined. We performed a genome-wide association study (GWAS) using over 850 male and female heterogeneous stock rats to identify genes underlying behaviors associated with OUD such as analgesia, as well as heroin-taking, refraining and seeking behaviors...

RATIONALE: Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is a novel molecule in development for treatment of substance use disorders, psychiatric comorbidities, and pain. OBJECTIVE: Characterize the preclinical profile of ITI-333 using pharmacological, behavioral, and physiological assays. METHODS: Cell-based assays were used to measure receptor binding and intrinsic efficacy of ITI-333; animal models were employed to assess effects on opioid reinstatement, precipitated oxycodone withdrawal, and drug abuse liability...

Substance abuse is a widespread problem in the United States and worldwide. This use within the pregnant population is thought to reflect a pattern similar to the general population, with estimates of 10% to 15% of pregnant women experiencing substance abuse. Illicit substance use during pregnancy has increased substantially during the past decade in the United States. During the past decade, novel or atypical substances have emerged and become increasingly popular. Occurrences of toxicity and untoward fetal effects from designer drug use must be kept high on the watch list for all who practice in maternal-fetal, newborn, and emergency departments...

ETHNOPHARMACOLOGICAL RELEVANCE: Herbs of the genus Juniperus (family Cupressaceae) have been commonly used in ancestral folk medicine known as "Al'Araar" for treatment of rheumatism, diabetes, inflammation, pain, and fever. Bioassay-guided isolation of bioactives from medicinal plants is recognized as a potential approach for the discovery of novel drug candidates. In particular, non-addictive painkillers are of special interest among herbal phytochemicals. AIM OF THE STUDY: The current study aimed to assess the safety of J...

OBJECTIVES: Describing our institution's off-label use of gabapentin to treat irritability after superior cavopulmonary connection surgery and its impact on subsequent opiate and benzodiazepine requirements. METHODS: This is a single-center retrospective cohort study including infants who underwent superior cavopulmonary connection operation between 2011 and 2019. RESULTS: Gabapentin was administered in 74 subjects (74/323, 22.9%) during the observation period, with a median (IQR) starting dose of 5...

Cherubism (OMIM 118400) is a rare craniofacial disorder in children characterized by destructive jawbone expansion due to the growth of inflammatory fibrous lesions. Our previous studies have shown that gain-of-function mutations in SH3 domain-binding protein 2 (SH3BP2) are responsible for cherubism and that a knock-in mouse model for cherubism recapitulates the features of cherubism, such as increased osteoclast formation and jawbone destruction. To date, SH3BP2 is the only gene identified to be responsible for cherubism...

Genome-wide association studies (GWAS) of psychiatric disorders (PD) yield numerous loci with significant signals, but often do not implicate specific genes. Because GWAS risk loci are enriched in expression/protein/methylation quantitative loci (e/p/mQTL, hereafter xQTL), transcriptome/proteome/methylome-wide association studies (T/P/MWAS, hereafter XWAS) that integrate xQTL and GWAS information, can link GWAS signals to effects on specific genes. To further increase detection power, gene signals are aggregated within relevant gene sets (GS) by performing gene set enrichment (GSE) analyses...

OBJECTIVE: Sphincter of Oddi Disorders (SOD) are contentious conditions in patients whose abdominal pain, idiopathic acute pancreatitis (iAP) might arise from pressurization at the sphincter of Oddi. The present study aimed to measure the benefit of sphincterotomy for suspected SOD. DESIGN: Prospective cohort conducted at 14 U.S. centers with 12 months follow-up. Patients undergoing first-time ERCP with sphincterotomy for suspected SOD were eligible: pancreatobiliary-type pain with or without iAP...

UNLABELLED: The pattern of neck injuries sustained in fatal cases of external compression to the neck is recorded during Post Mortem Examinations (PME), to assist in the interpretation of the circumstances that led to death. In this study, the PMEs performed for 298 cases of hanging and strangulation occurring between 2016 and 2020 in Ireland were retrospectively reviewed for the purpose of recording and collating the external and internal neck injuries observed during each PME, as well as the toxicology results for each decedent...

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most frequent and debilitating conditions leading to gastroenterological referrals. However, recommended treatments remain limited, yielding only limited therapeutic gains. Chitin-glucan (CG) is a novel dietary prebiotic classically used in humans at a dosage of 1.5-3.0 g/d and is considered a safe food ingredient by the European Food Safety Authority. To provide an alternative approach to managing patients with IBS, we performed preclinical molecular, cellular, and animal studies to evaluate the role of chitin-glucan in the main pathophysiological mechanisms involved in IBS...

Background: There is growing evidence that the treatment of several mental disorders can potentially benefit from activation of delta-opioid receptors. In the future, delta-agonists with a safe pharmacological profile can be used for the treatment of mood disorders in pregnant women. However, the data on prenatal exposure to delta-opioid agonists are missing. The present study is aimed to test the hypothesis that the activation of delta-opioid receptors during gravidity has positive effects on the behaviour accompanied by changes in glutamate and monoamine neurotransmission...

The design of bifunctional compounds is a promising approach toward the development of strong analgesics with reduced side effects. We here report the optimization of the previously published lead peptide KGFF09 , which contains opioid receptor agonist and neuropeptide FF receptor antagonist pharmacophores and is shown to induce potent antinociception and reduced side effects. We evaluated the novel hybrid peptides for their in vitro activity at MOP, NPFFR1, and NPFFR2 and selected four of them ( DP08/14/32/50 ) for assessment of their acute antinociceptive activity in mice...

BACKGROUND AND OBJECTIVES: The provider-patient relationship is integral to medical practice and health outcomes, particularly among vulnerable patient populations. This study compared the provider-patient relationship among pregnant patients with opioid-use disorder (OUD), who did or did not have a history of moderate to severe trauma. METHODS: This was an exploratory data analysis of 119 patients enrolled in the Support Models for Addiction Related Treatment trial...

IMPORTANCE: The rise of fentanyl and other high-potency synthetic opioids across US and Canada has been associated with increasing hospitalizations and unprecedented overdose deaths. Hospitalization is a critical touchpoint to engage patients and offer life-saving opioid use disorder (OUD) care when admitted for OUD or other medical conditions. OBSERVATIONS: Clinical best practices include managing acute withdrawal and pain, initiating medication for OUD, integrating harm reduction principles and practices, addressing in-hospital substance use, and supporting hospital-to-community care transitions...

INTRODUCTION: Major depression is a common, disabling mental health condition associated with the highest disease burden for any neuropsychiatric disorder worldwide according to the WHO. Due to the imperfect efficacy and tolerability profiles of existing treatments, investigational compounds in novel treatment classes are needed. Opioid-receptor antagonists are a potential new class of treatments currently under investigation. AREAS COVERED: Major depressive disorder is first overviewed...

BACKGROUND AND AIM: Bromazolam, a novel designer benzodiazepine (NBD), exhibits potent sedative, hypnotic and anxiolytic effects, raising concerns regarding its potential for misuse and fatal outcomes, particularly when combined with opioids such as fentanyl. Despite limited documented fatalities globally, its use poses a significant threat, exacerbated by under-reporting and a lack of routine testing. This study analysed NBD-related deaths in a major US city over a 4-year period. METHODS: Analysis of accidental overdose deaths involving NBDs in San Francisco, CA, USA from 2020 to 2023, was performed utilizing medico-legal death investigations including comprehensive forensic toxicology, pathology and demographic information...