Novel Opioid

In this paper, we present the development and the validation of a novel index of nociception/anti-nociception (N/AN) based on skin impedance measurement in time and frequency domain with our prototype AnspecPro device. The primary objective of the study was to compare the Anspec-PRO device with two other commercial devices (Medasense, Medstorm). This comparison was designed to be conducted under the same conditions for the three devices. This was carried out during total intravenous anesthesia (TIVA) by investigating its outcomes related to noxious stimulus...

Opioid administration is particularly challenging in the perioperative period. Computerized-based Clinical Decision Support Systems (CDSS) are a promising innovation that might improve perioperative pain control. We report the development and feasibility validation of a knowledge-based CDSS aiming at optimizing the management of perioperative pain, postoperative nausea and vomiting (PONV), and laxative medications. This novel CDSS uses patient adaptive testing through a smartphone display, literature-based rules, and individual medical prescriptions to produce direct medical advice for the patient user...

Sternal wound complications following sternotomy need a multidisciplinary approach in high-risk postoperative cardiac surgical patients. Poorly controlled pain during surgical management of such wounds increases cardiovascular stress and respiratory complications. Multimodal analgesia including intravenous opioids, non-opioid analgesics, and regional anesthesia techniques, like central neuraxial blocks and fascial plane blocks, have been described. Pecto-intercostal fascial plane block (PIFB), a novel technique, has been effectively used in patients undergoing cardiac surgery...

BACKGROUND: The opioid crisis continues to pose significant challenges to global public health, necessitating the development of novel interventions to support individuals in managing their substance use and preventing overdose-related deaths. Mobile health (mHealth), as a promising platform for addressing opioid use disorder, requires a comprehensive understanding of user perspectives to minimize barriers to care and optimize the benefits of mHealth interventions. OBJECTIVE: This study aims to synthesize qualitative insights into opioid users' acceptability and perceived efficacy of mHealth and wearable technologies for opioid use disorder...

Preclinical research has demonstrated the efficacy of CB1 receptor (CB1R) antagonists in reducing drug-taking behavior. However, clinical trials with rimonabant, a CB1R antagonist with inverse agonist profile, failed due to severe adverse effects, such as depression and suicidality. As a result, efforts have shifted towards developing novel neutral CB1R antagonists without an inverse agonist profile for treating substance use disorders. Here, we assessed AM6527, a CB1R neutral antagonist, in addiction animal models...

BACKGROUND AND AIMS: Xylazine is a non-opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. METHODS: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co-detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner...

The surge in opioid-related deaths, driven predominantly by fentanyl and its synthetic derivatives, has become a critical public health concern, which is particularly evident in the United States. While the situation is less severe in Europe, the European Monitoring Centre for Drugs and Drug Addiction reports a rise in drug overdose deaths, with emerging concerns about the impact of fentanyl-related molecules. Synthetic opioids, initially designed for medical use, have infiltrated illicit markets due to their low production costs and high potency, with carfentanil posing additional threats, including potential chemical weaponization...

Hydrogen Peroxide (H2 O2 ) is a central oxidant in redox biology due to its pleiotropic role in physiology and pathology. However, real-time monitoring of H2 O2 in living cells and tissues remains a challenge. We address this gap with the development of an optogenetic hydRogen perOxide Sensor (oROS), leveraging the bacterial peroxide binding domain OxyR. Previously engineered OxyR-based fluorescent peroxide sensors lack the necessary sensitivity and response speed for effective real-time monitoring. By structurally redesigning the fusion of Escherichia coli (E...

BACKGROUND: Affecting >20million people in the U.S., including 4 % of all hospitalized patients, substance use disorder (SUD) represents a growing public health crisis. Evaluating a national cohort, we aimed to characterize the association of concurrent SUD with perioperative outcomes and resource utilization following elective abdominal operations. METHODS: All adult hospitalizations entailing elective colectomy, gastrectomy, esophagectomy, hepatectomy, and pancreatectomy were tabulated from the 2016-2020 National Inpatient Sample...

Understanding the function of the kappa opioid receptor (KOP) is crucial for the development of novel therapeutic interventions that target KOP for the treatment of pain, stress-related disorders and other indications. Activation of KOP produces diuretic effects in rodents and man. Sex is a vital factor to consider when assessing drug response in pre-clinical and clinical studies. In this study, the diuretic effect of the KOP agonist, U50488 (1-10 mg/kg), was investigated in both adult female and male Wistar rats that were either normally hydrated or water-loaded...

Painful musculoskeletal disorders such as intervertebral disc (IVD) degeneration associated with chronic low back pain (termed "Discogenic back pain", DBP), are a significant socio-economic burden worldwide and contribute to the growing opioid crisis. Yet there are very few if any successful interventions that can restore the tissue's structure and function while also addressing the symptomatic pain. Here we have developed a novel non-viral gene therapy, using engineered extracellular vesicles (eEVs) to deliver the developmental transcription factor FOXF1 to the degenerated IVD in an in vivo model...

BACKGROUND: Considering the enormous burden represented by the opioid use disorder (OUD), it is important to always consider, when implementing opioid agonist therapy (OAT), the potential impact on patient's adherence, quality of life, and detoxification. Thus, the purpose of the study is to evaluate how the introduction of a novel OAT approach influences these key factors in the management of OUD. CASE PRESENTATION: This article marks the pioneering use of OAT through buprenorphine implant in Europe and delves into the experience of six patients diagnosed with OUD at a relatively young age...

BACKGROUND: Long-acting injectable buprenorphine (LAIB) formulations are a novel treatment approach in opioid agonist treatment (OAT), which provide patients with a steady dose administered weekly or monthly and thus reduce the need for frequent clinic visits. Several studies have analyzed patient experiences of LAIB but the perspective of OAT staff is unknown. This study aimed to explore how healthcare staff working in OAT clinics in Sweden perceive and manage treatment with LAIB. METHODS: Individual qualitative interviews were conducted with OAT physicians (n = 10) in tandem with nine focus group sessions with OAT nurses and other staff categories (n = 41)...

Some new hemorphin-4 analogs with structures of Xxx-Pro-Trp-Thr-NH2 and Tyr-Yyy-Trp-Thr-NH2 , where Xxx is 2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoic acid or 2-amino-3-(4-dibenzylamino-2,6-dimethylphenyl)propanoic acid, and Yyy is (2S,4S)-4-amino-pyrrolidine-2-carboxylic acid, were synthesized and characterized by electrochemical and spectral analyses. In vivo anticonvulsant and antinociceptive activities of peptide derivatives were studied after intracerebroventricular injection in mice. The therapeutic effects of the modified peptides on seizures and pain in mice were evaluated to provide valuable insights into the potential applications of the novel compounds...

The complex impacts of prolonged morphine exposure continue to be a significant focus in the expanding area of addiction studies. This research investigates the effectiveness of a combined treatment using Cabergoline and Mdivi-1 to counteract the neuroadaptive changes caused by in vitro morphine treatment. The impact of Methadone, Cabergoline, and a combination of Cabergoline and Mdivi-1 on the cellular and molecular responses associated with Morphine-induced changes was studied in human Neuroblastoma (SK-N-MC) and Glioblastoma (U87-MG) cell lines that were exposed to prolong Morphine treatment...

INTRODUCTION: Neuropathic pain (NP) significantly impacts quality of life and often coexists with affective disorders such as anxiety and depression. Addressing both NP and its psychiatric manifestations requires a comprehensive understanding of therapeutic options. This study aimed to review the main pharmacological and non-pharmacological treatments for NP and comorbid affective disorders to describe their mechanisms of action and how they are commonly used in clinical practice. METHODS: A review was conducted across five electronic databases, focusing on pharmacological and non-pharmacological treatments for NP and its associated affective disorders...

Fentanyl, a critical component of illicit drugs, poses a severe threat to public health, exacerbating the drug problem due to its potential fatality. Herein, we present two novel haptens designed with different attachment sites conjugated to keyhole limpet hemocyanin (KLH), aiming to develop an efficacious vaccine against fentanyl. KLH-Fent-1 demonstrated superior performance over KLH-Fent-2 in antibody titer, blood-brain distribution, and antinociceptive tests. Consequently, we immunized mice with KLH-Fent-1 to generate fentanyl-specific monoclonal antibodies (mAbs) using the hybridoma technique to compensate for the defects of active immunization in the treatment of opioid overdose and addiction...

BACKGROUND: Communities That HEAL (CTH) is a novel, data-driven community-engaged intervention designed to reduce opioid overdose deaths by increasing community engagement, adoption of an integrated set of evidence-based practices, and delivering a communications campaign across healthcare, behavioral-health, criminal-legal, and other community-based settings. The implementation of such a complex initiative requires up-front investments of time and other expenditures (i.e., start-up costs)...

Opioid drugs are potent analgesics that mimic the endogenous opioid peptides, endorphins and enkephalins, by activating the µ-opioid receptor. Opioid use is limited by side effects, including significant risk of opioid use disorder. Improvement of the effect/side effect profile of opioid medications is a key pursuit of opioid research, yet there is no consensus on how to achieve this goal. One hypothesis is that the degree of arrestin-3 recruitment to the µ-opioid receptor impacts therapeutic utility...

BACKGROUND: Olanzapine/Samidorphan (Lybalvi®) is a novel oral agent for the treatment of schizophrenia and bipolar I disorder. It was designed to reduce weight gain associated with olanzapine. Samidorphan is an analog of naltrexone, initially intended to treat substance use disorders by antagonizing mu, delta, and kappa opioid receptors. CASE REPORT: We present the case of a 36-year-old who took their first dose of olanzapine/samidorphan shortly before calling for emergency services...