The opioid epidemic continues to be a major public health crisis in the United States, and nalmefene has recently emerged as an alternative opioid overdose reversal agent. However, little is known about pharmacists' awareness and beliefs regarding nalmefene use and distribution. Therefore, the purpose of this study was to assess Alabama pharmacists' knowledge, perceptions, and behavioral intentions related to nalmefene. This study used a cross-sectional survey design. Practicing pharmacists in the state of Alabama were eligible to participate, and were recruited through the Alabama Board of Pharmacy email listserv. An anonymous online survey was distributed via email, and respondents were eligible to enter a lottery for one of five $100 electronic gift cards. The survey instrument was developed by the investigators, adapted from prior overdose reversal literature and informed by the Theory of Planned Behavior. Primary outcome measures included: knowledge of nalmefene (12 items); perceived barriers regarding nalmefene stocking and recommendations (19 items); and Theory of Planned Behavior concepts including attitudes (15 items), subjective norms (perceived social support) (six items), perceived behavioral control (confidence in ability to stock or recommend nalmefene) (11 items), and behavioral intentions surrounding nalmefene stocking and recommendations (13 items). Outcomes were measured via multiple-choice (objective knowledge) and Likert-type scale (1 = strongly disagree, 5 = strongly agree) questions. Differences in mean scale scores across pharmacy setting (pharmacists employed in inpatient versus outpatient settings), community pharmacy type (chain vs. independent), and geographic location (rural vs. urban) were analyzed using two-sided Mann-Whitney U tests for non-parametric data or t-tests for parametric data, as appropriate. Multiple linear regression analyses examined associations between TPB constructs and pharmacists' intentions to stock or recommend nalmefene over the next six months. All data were analyzed using SPSS statistical software version 29 with an alpha of 0.05. There were 119 pharmacist respondents (n = 25 inpatient, n = 94 outpatient). The majority were female (68.1%), White (94.1%), and worked in community settings (35.3% independent, 10.9% corporate, 10.1% big-box, 5.0% grocery). Median age was 42 years (IQR: 36-51). Awareness of nalmefene was low: only 39.5% had heard of it and 5.9% had seen it in practice. Inpatient versus outpatient pharmacists reported higher subjective norms external to the workplace (median [IQR]: 3.00 [2.33, 3.58] vs. 2.33 [1.67, 3.00]; p = 0.004) as well as subjective knowledge (mean [SD]: 2.96 [0.94] vs. 2.55 [0.74]; p = 0.023), while outpatient versus inpatient pharmacists reported higher perceived barriers related to fiscal/logistical concerns (mean [SD]: 3.45 [0.59] vs. 3.07 [0.66]; p = 0.009). Among community pharmacists, stocking and procurement confidence was higher among independent versus chain pharmacists (3.75 [3.00-4.17] vs. 3.17 [2.67-3.92]; p = 0.026). Furthermore, external workplace norms among urban pharmacists were higher than among rural pharmacists (2.50 [2.00-3.00] vs. 2.33 [1.67, 2.67]; p = 0.027), while stocking and procurement confidence was higher among rural than urban pharmacists (3.83 [2.83-4.50] vs. 3.17 [2.67-4.00]; p = 0.034). In adjusted reduced regression models, perceived behavioral control regarding nalmefene stocking and procurement (B = 0.189, 95% CI: 0.049, 0.329; p = 0.009), subjective norms external to the workplace (B = 0.232, 95% CI: 0.047, 0.418; p = 0.015), and interprofessional recommendation attitudes (B = 0.237, 95% CI: 0.037, 0.437; p = 0.021) positively predicted nalmefene implementation intentions. These findings suggest practice-setting differences that could be further explored for optimal implementation of nalmefene distribution and access, and highlight the need for targeted education, interprofessional collaboration, procurement guidance, and workflow tools to improve pharmacist preparedness for nalmefene services.

Opioid receptor antagonists, particularly naltrexone and nalmefene, are among the best-supported pharmacotherapies for alcohol use disorder (AUD), yet their clinical efficacy remains modest and highly heterogeneous. The mechanisms through which transient opioid receptor blockade produces sustained therapeutic benefit remain incompletely understood. Classical explanations emphasize attenuation of alcohol reward and suppression of craving, whereas extinction-based models propose that therapeutic effects emerge when alcohol consumption occurs under opioid receptor blockade, leading to weakening of conditioned drinking behavior. Clinical findings from targeted or "as-needed" treatment paradigms are broadly consistent with this interpretation. However, available observations are not fully explained by extinction alone. Preclinical animal studies suggest that subsequent alcohol drinking may depend critically on the timing of antagonist administration relative to alcohol exposure, including effects observed when opioid antagonists are administered immediately after drinking. Such findings raise the possibility that post-reward memory processes, including interference with reward-memory consolidation or reconsolidation, may contribute to therapeutic effects. Alternative explanations, including conditioned taste aversion, must also be considered, although the broader human literature more strongly supports modulation of reward and craving than generalized aversion. This mini-review integrates preclinical, clinical, and contemporary memory-neuroscience perspectives on opioid antagonist treatment in AUD. Improved understanding of these timing-dependent mechanisms, and their potential translational relevance to humans, may help explain clinical heterogeneity and guide the development of more targeted pharmacotherapeutic strategies.

Long-acting injectable buprenorphine is one option for the management of opioid use disorder. The United States Food and Drug Administration has approved two brands for monthly injection, Sublocade ® (Indivior, North Chesterfield, VA, USA) and Brixadi® (Braeburn, Plymouth Meeting, PA, USA). We report the development of encephalopathy following administration of Brixadi®. Consent was obtained from the patient. A 62-year-old patient with a history of current methamphetamine and prior fentanyl abuse, chronic pain due to lumbar radiculopathy presented to the emergency department with three days of altered mental status. She received subcutaneous Brixadi® 128 mg monthly formulation three days prior at an outpatient addiction medicine clinic, reportedly to treat simultaneously presumptive incidental opioid dependence from contaminated methamphetamine use due to serial positive urine fentanyl testing over the prior three visits, most recently 3 months prior, and chronic low back pain. Urine fentanyl testing on the date of presentation was negative. She developed persistent altered mentation and somnolence starting two hours after injection.

Background: Alcohol use disorder (AUD) is a grave mental health condition that can result in significant health and social consequences. The medications Naltrexone and Nalmefene are indicated for the treatment of AUD, with Naltrexone having received the most extensive research attention. Methods: The majority of papers assessing universal measures of alcohol consumption employed two primary metrics: total alcohol consumption (TAC) and the number of days per month where individuals engaged in heavy drinking (HDD). Indicators pertaining to the maintenance of complete abstinence were excluded due to the absence of sufficient data. The safety of both substances was also assessed, as were the frequency of side effects and independent patient dropout. The study also incorporated practical factors of the therapy, such as the route of administration, dosage regimen, and the drug's patient convenience, which can have a significant impact on adherence to therapy. Results: Nalmefene, administered in an "as needed" regimen, demonstrated statistically significant activity in reducing HDD and total alcohol consumption (TAC) among patients with AUD, particularly those with elevated World Health Organization (WHO) DRL risk. Preliminary findings from the ESENSE1 (Efficacy of Nalmefene in Alcohol Dependence; the first phase III study), ESENSE 2 (Efficacy of Nalmefene in Alcohol Dependence, the second phase III study), and SENSE (the final phase III long term-safety and cost-effectiveness study) studies indicate a substantial decrease in HDD and TAC following the initial month of treatment. These effects persist throughout the subsequent follow-up period. Several Japanese studies have corroborated the effectiveness of Nalmefene, demonstrating its efficacy across both short-term and long-term applications. Furthermore, these studies have substantiated its safety profile, indicating that there is no inherent risk of addiction or the emergence of withdrawal symptoms. The mild nature of adverse events (most commonly nausea and dizziness) led to a relatively low discontinuation rate of Nalmefene treatment. A subsequent study, employing a recognized methodology, corroborated the efficacy of psychosocial support in enhancing treatment outcomes. Meta-analyses demonstrate that Naltrexone exhibits comparable efficacy in reducing the frequency and severity of alcohol consumption. In select populations, the injectable form (LAI) of this pharmaceutical agent facilitates less frequent dosing, which is advantageous for the treatment process. A comparison of Nalmefene and Naltrexone reveals that the latter does not demonstrate a significant impact on the likelihood of individuals returning to heavy alcohol consumption. Conclusions: In the treatment of AUD, both naltrexone and nalmefene have been shown to yield positive outcomes, particularly in terms of reducing the HDD and TAC. According to the World Health Organization (WHO) classification, Nalmefene is indicated for individuals with a high risk of developing serious conditions. It has been demonstrated to produce rapid and sustained results while exhibiting a favorable safety profile, characterized by the absence of significant adverse effects. Naltrexone is a medication that has proven to be effective. LAI may have a positive impact on the efficacy of treatment.

Gambling disorder or pathological gambling is a psychiatric disorder with severe and wide-ranging consequences for the affected individual and their surroundings. While no pharmacological treatment has yet been officially approved for treatment, various drugs have been investigated to date. An electronic literature search was conducted in PubMed to identify open-label trials, randomized controlled trials, meta-analyses, other reviews and case reports. In addition, the ClinicalTrials.gov registry was reviewed to identify recent advancements, investigational drug candidates, and ongoing or forthcoming clinical research related to this topic. In this review we summarize and compare Fluvoxamine, Paroxetine, Sertraline, Citalopram, Bupropion, Nefazodone, Naltrexone, Nalmefene, Naloxone, Lithium, Valproate, Topiramate, Olanzapine, N-acetylcysteine, Disulfiram, Acamprosate, Memantine, Amantadine, Gabapentinoids, Modafinil, GLP-1 receptor agonists and Ketamine/Esketamine. From the above-mentioned substances, many have shown promising results in the treatment of gambling disorder, particularly opioid antagonists. However, the small number of studies on the respective drugs, as well as inconsistent designs and contradictory results, limit the significance and clinical applicability of the findings. Here we discuss the most promising drugs, neurobiological pathomechanisms of gambling disorder and potential methodological designs for future studies on this topic.

Nalmefene is an opioid antagonist used in OPVEE[®] nasal spray approved for use in patients 12 years of age and older. To support future clinical studies in younger pediatric populations, 2 GLP juvenile rat studies were conducted to assess the safety of nalmefene and its associated systemic exposure. Nalmefene was administered daily via intranasal instillation from postnatal day (PND) 7 to PND 28 (corresponding to birth through approximately 3 years) with recovery to PND 91, or from PND 22 to PND 70 (2 years to adolescent) with recovery to PND 114. Exposures on PND 7 were 28-40 times higher than those on PND 28, and exposures on PND 22 were 3-5 times higher than those on PND 70. Exposures on PND 28 were comparable to those on PND 70, attaining adult levels. Considering the extensive metabolism and urinary clearance of nalmefene, these findings are consistent with the maturation of metabolic and urinary clearance pathways during early development. No effects were observed on clinical signs, ophthalmology, food consumption, femur length, sperm parameters, immune responses, or neurodevelopment as assessed by neurohistopathology and neurobehavioral testing for locomotor activity, sensory function, or learning and memory. There were no macroscopic or microscopic findings indicative of target organ, systemic, or neurotoxicity. The NOAELs were 4.25 mg/dose, the highest doses tested. On PND 28, Cmax (224 ng/mL) and AUC (311 ng·hr/mL) were 21- and 8-fold higher than those reported in human adults, respectively. The AUC-based safety margins in pediatric patients were estimated to range from 1.5 to 12, depending on the age group (birth-12 years; 3-40 kg).

Alcohol use disorders are common and contribute significantly to the global burden of disease. The treatment of alcohol dependence includes the acute withdrawal phase and the post-acute rehabilitation phase. The primary goal of post-acute treatment is long-term abstinence, although reduction of alcohol consumption is also recognized as an intermediate goal. In addition to psychosocial and psychotherapeutic interventions, the use of medications is recommended. In Switzerland, four medications (acamprosate, naltrexone, nalmefene, and disulfiram) are approved for post-acute treatment. Their efficacy in reducing relapse risk, drinking days, and overall alcohol consumption is well established. Baclofen, topiramate, and gabapentin are used "off-label", but sufficient evidence of their effectiveness is still lacking. Innovative approaches such as cannabidiol, psilocybin, and glucagon-like peptide-1 receptor agonists show promising therapeutic potential, which needs to be confirmed in further clinical studies. The use of pharmacological interventions can help improve patient outcomes, reduce the need for inpatient treatment, and lower healthcare costs.