Selincro (nalmefene oral) / Lundbeck, Otsuka, Acorda - LARVOL DELTA

Safety and Persistence of Nalmefene Treatment for Alcohol Dependence. Results from Two Post-authorisation Safety Studies. (PubMed, Alcohol Alcohol) - "Despite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits."

Clinical • Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Insomnia • Psychiatry • Sleep Disorder

Use of Nalmefene in Routine Practice: Results from a French Prospective Cohort Study and a National Database Analysis. (PubMed, Alcohol Alcohol) - "In this analysis of French routine practice, patients with alcohol dependence treated with nalmefene showed reduced alcohol consumption, and nalmefene was generally well tolerated."

Clinical • Journal • Addiction (Opioid and Alcohol)

Patient Driven Recovery With Nalmefene and Coaching (clinicaltrials.gov) - P1; N=10; Completed; Sponsor: Yale University; Phase classification: P2 ➔ P1

Clinical • Phase classification

Effect of Nalmefene on the Quality of Resuscitation in Patients Under General Anesthesia (clinicaltrials.gov) - P4; N=520; Not yet recruiting; Sponsor: RenJi Hospital

Clinical • New P4 trial • Anesthesia

Title: Effect of Opioid Receptor Modulation on Alcohol Self-Administration and Neural Response to Alcohol Cues in Heavy Drinkers: Role of OPRM1 Gene Variation (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA); Trial primary completion date: Dec 2020 ➔ Dec 2021

Trial primary completion date

Four cases of alcoholic liver cirrhosis in alcohol-dependent patients treated with nalmefene (PubMed, Nihon Shokakibyo Gakkai Zasshi) - "Their alcohol consumption was reduced, which led to an improvement in liver function. Nalmefene provides a clinical benefit, constitutes a potential pharmacological treatment paradigm in terms of the treatment goal and dosing regimen, and addresses an unmet medical need in patients with alcohol dependence who need to reduce their alcohol consumption."

Clinical • Journal • Addiction (Opioid and Alcohol) • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis

Real-world effectiveness of pharmacological treatments of alcohol use disorders in a Swedish nation-wide cohort of 125 556 patients. (PubMed, Addiction) - "Naltrexone as monotherapy and when combined with disulfiram and acamprosate appears to be associated with lower risk of hospitalization due to any and alcohol-related causes, compared with no use of alcohol use disorder (AUD) medication. Acamprosate monotherapy and benzodiazepine use appear to be associated with increased risk of AUD-associated hospitalization."

Clinical • Journal • Real-World Evidence • Addiction (Opioid and Alcohol)

Morphine promotes tumorigenesis and cetuximab resistance via EGFR signaling activation in human colorectal cancer. (PubMed, J Cell Physiol) - "The cell phenotype includes proliferation, migration, invasion, and drug resistance, which may be reversed by MOR knockdown or adding nalmefene, the MOR receptor antagonist. Furthermore, we verified that EGFR inhibition by cetuximab strongly reversed the protumoral effects of morphine in vitro and in vivo. Collectively, we provide evidence that morphine-EGFR signaling might be a promising therapeutic target for CRC patients, especially for cetuximab-resistant CRC patients."

Journal • Addiction (Opioid and Alcohol) • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pain • Solid Tumor

Unique Pharmacological Properties of the Kappa Opioid Receptor Signaling Through Gαz as Shown with Bioluminescence Resonance Energy Tranfer. (PubMed, Mol Pharmacol) - "Although the full agonists U50,488, salvinorin A, nalfurafine, and dynorphin peptides were equally efficacious regardless of the Gα subunit present, the concentration-response curves were leftward shifted when the KOR was signaling through Gαz compared with other Gαi/o subunits. In contrast, the Gα subunit distinctly affected both the efficacy and potency of partial kappa agonists, such as the benzomorphans, and the classic mu opioid antagonists, naloxone, naltrexone, and nalmefene...Opioid signaling was more potent through Gαz compared with other Gα proteins. These observations suggest that Gαz may impact opioid pharmacology and cellular physiology more than previously thought."

Journal

Clinically utilized kappa-opioid receptor agonist nalfurafine combined with low-dose naltrexone prevents alcohol relapse-like drinking in male and female mice. (PubMed, Brain Res) - "Nalmefene (NMF, clinically utilized KOP-r partial agonist with MOP-r antagonism) was used as a reference compound for the effects on mouse ADE of new NFF + NTX combination. NMF prevented the ADE in both sexes, while selective KOP-r antagonist nor-BNI had no effect. Our new study suggests that a combination of clinically-utilized, potent KOP-r agonist NFF with low-dose NTX has therapeutic potential in alcohol "relapse" treatment."

Journal • Addiction (Opioid and Alcohol) • Anesthesia

Countermeasures for preventing and treating opioid overdose. (PubMed, Clin Pharmacol Ther) - "This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: 1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; 2) methocinnamox, a novel opioid receptor antagonist; 3) covalent naloxone nanoparticles; 4) serotonin (5-HT) receptor agonists; 5) fentanyl-binding cyclodextrin scaffolds; 6) detoxifying biomimetic "nanosponge" decoy receptors; and 7) antibody-based strategies. These strategies could also be applied to treat opioid use disorder (OUD)."

Journal • Review • Addiction (Opioid and Alcohol) • Allergy • CNS Disorders • Immunology • Infectious Disease

Nalmefene, Baclofen and Impulsivity in Subjects With Alcohol Use Disorder and Healthy Control Subjects (clinicaltrials.gov) - P2; N=37; Completed; Sponsor: Prof. Daniele Zullino; Recruiting ➔ Completed; N=60 ➔ 37

Clinical • Enrollment change • Trial completion

Open-label Study with Nalmefene as Needed Use in Alcohol-Dependent Patients with Evidence of Elevated Liver Stiffness and/or Hepatic Steatosis. (PubMed, Alcohol Alcohol) - "Patients treated with nalmefene for 12 weeks had reductions in alcohol consumption by ~50% relative to baseline and showed trends to improvement in liver stiffness and CAP."

Clinical • Journal • Addiction (Opioid and Alcohol)

The effects of nalmefene on emotion processing in alcohol use disorder - A randomized, controlled fMRI study. (PubMed, Eur Neuropsychopharmacol) - "Attentional bias analyses revealed an interaction effect by trend, which was driven by a significant effect in a sub-analysis showing increased attentional shift towards happy compared to fearful facial expressions under nalmefene. Nalmefene increased brain activation in areas responsible for empathy, social cognition and behavior, which might help alleviating the reinforcing properties of alcohol."

Clinical • Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Mood Disorders

Medication Development for Alcohol Use Disorder: A Focus on Clinical Studies. (PubMed, Handb Exp Pharmacol) - "Disulfiram, naltrexone (oral and long-acting), and acamprosate are approved by the US Food and Drug Administration (FDA) to treat patients with AUD. These medications are also approved in other countries, including in Europe, where the European Medicines Agency (EMA) also approved nalmefene for AUD...Therefore, research is needed to expand the armamentarium of medications that clinicians can use to treat their patients, as well as to better develop personalized approaches. This book chapter reviews other medications, beyond those approved by the FDA, that have shown efficacy in clinical trials, as well as medications which are still in the early stages of evaluation in human studies."

Clinical • Journal • Addiction (Opioid and Alcohol)

[VIRTUAL] Evaluation of the efficacy of combined, nalmefene and cognitive behavioral therapy, for gambling disorder (ECNP 2020) - "Evaluation of the patient’s comorbid conditions is important when planning a treatment approach, because naltrexone may be particularly important in GD and substance use disorders dual diagnosis, or when there is a positive familial history of alcohol dependence, while lithium may be preferred in patients with bipolar disorder and GD, and serotonin reuptake inhibitors may decrease GD severity in patients with comorbid mood or anxiety disorders [3,4]. Other therapies for GD may be extrapolated from substance use disorders available treatments, and such options may be topiramate and other mood stabilizers, anxiolytics, antipsychotics, psychostimulants, etc [3]... Nalmefene combined with cognitive-behavioral therapy is efficient and well-tolerated in patients presenting GD. The effect of nalmefene was observed over the core GD symptoms, but also the quality of life, clinical global impression, and global functionality improved after 12 weeks."

Clinical • Addiction (Opioid and Alcohol) • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review. (PubMed, Int J Mol Sci) - "Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction."

Journal • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Mood Disorders • Psychiatry • Transplantation

Nalmefene alleviates the neuroimmune response to repeated binge-like ethanol exposure: A TSPO PET imaging study in adolescent rats. (PubMed, Addict Biol) - "Nalmefene may protect against the neuroinflammatory response and overall toxicity associated with binge drinking. [ F]DPA-714 PET imaging can be used to noninvasively address the neuroimmune impact of ethanol exposure and its modulation by pharmacological strategies in vivo, with translational perspectives."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Immunology • Psychiatry • TLR4

[VIRTUAL] Modified Julia olefination of naltrexone and efficient synthesis of its reagent sulfones (ACS-Fall 2020) - "The [{MoO(O2)2}2(μ-O)]2– catalyst that was used to synthesize the sulfones has shown to be very efficient, low cost, robust, clean, and very convenient to use, even in comparison to other catalysts used for this reaction under similar conditions, such as Na2WO4Only 0.005 equivalents of catalyst was required per equivalent of sulfide to synthesize the target sulfones at yields approaching 100%. The attempted synthesis of nalmefene using these sulfones shows promise; however, more research is needed to optimize the reaction conditions."

Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry

Alcohol dependence and opioid receptor -Pharmacological profile of nalmefene (PubMed, Nihon Yakurigaku Zasshi) - "These results suggest that nalmefene modulates the alcohol-induced euphoric/dysphoric mood via opioid system and thereby contribute to reduction in alcohol consumption in patients with alcohol dependence. Here, we summarize the implications of opioid system in alcohol dependence and pharmacological profiles of nalmefene in preclinical and clinical studies."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Mental Retardation • Psychiatry

Patient Driven Recovery With Nalmefene and Coaching (clinicaltrials.gov) - P2; N=10; Completed; Sponsor: Yale University; Recruiting ➔ Completed; N=30 ➔ 10

Clinical • Enrollment change • Trial completion

Update Psychopharmacotherapy. (PubMed, Med Monatsschr Pharm) - "...Lurasidon and the new multimodal antidepressant vortioxetine demonstrating clinical efficacy in the improvement of cognition have been withdrawn from the German market due to economic reasons based on an official committee judgement „missing additional benefit“. Among new substances introduced are the selective opioid modulator nalmefene for reduction of alcohol consumption, the selective alpha-2-receptor agonist guanfacine for ADHS treatment in child and youth psychiatry, the older antidepressant milnacipran and the glucagon-like-peptide-1-receptor agonist liraglutide for treatment of adipositas. In the USA the atypical antipsychotics cariprazine and brexpiprazole have been released. The introduction of the long acting depot antipsychotics aripiprazole (1 month) and paliperidone (3 months) can be seen as major progress in the treatment of schizophrenia...Atypical antipsychotics like quetiapine are recommended now as add-on treatment for..."

Journal • Review • Biosimilar • CNS Disorders • Depression • Mood Disorders • Schizophrenia

Pharmacotherapy of alcohol withdrawal: update and new developments (PubMed, Nervenarzt) - "Apart from disulfiram, which is no longer marketed in Germany, the opioid antagonists naltrexone, nalmefene and the putative glutamate antagonist acamprosate are approved. Possible other drugs of interest for prophylaxis of alcohol dependence relapse are vareniclin, gabapentin, and topiramate, but so far none of them have received approval. In the light of the currently running revision of the German guidelines for the diagnosis and treatment of alcohol related disorders, an update on the pharmacotherapy of alcohol dependence is presented."

Journal • Review • Addiction (Opioid and Alcohol)

The recognition and management of protracted alcohol withdrawal may improve and modulate the pharmacological treatment of alcohol use disorder. (PubMed, J Psychopharmacol) - "Considering that PAW symptoms are mainly related to the neuro-adaptive changes of gamma-aminobutyric acid (GABA) and N-methyl-d-aspartate (NMDA) systems, naltrexone, nalmefene, and disulfiram may not be able to suppress the symptoms of PAW. After treatment of the acute phase of AWS, a more specifically pharmacological therapy able to suppress PAW symptoms could perhaps be used earlier and may be more helpful in preventing the risk of alcohol relapse, which remains higher during the first months of treatment. In light of this, medications acting on GABA and NMDA neurotransmitter systems to counterbalance the up-regulation of NMDA and the down-regulation of GABA could be employed in combination and started as soon as possible."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Mood Disorders

Opioid antagonists are associated with a reduction in the symptoms of schizophrenia: a meta-analysis of controlled trials. (PubMed, Neuropsychopharmacology) - "We conducted a meta-analysis of English language placebo-controlled clinical trials of naloxone, naltrexone, nalmefene, and buprenorphine in patients with schizophrenia to determine whether pan-opioid antagonists have therapeutic efficacy on positive, negative, or total symptoms...We also observed a significant effect of all drugs on all positive scales combined with both the random effects (g = 0.33; P = 0.015; k = 17; CI = 0.07-0.60) and bootstrap models (g = 0.32; P < 0.0001; k = 21; CI = 0.13-1.38). This evidence provides support for further testing in randomized clinical trials of a new class of non-D2-receptor drugs, based on opioid mechanisms, for the treatment of positive and negative symptoms of schizophrenia."

Journal • Retrospective data • CNS Disorders • Schizophrenia