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Neuropharmacology Nov 2023Ghrelin is a peptide that is produced by endocrine cells that are primarily localized in the stomach. Ghrelin receptors (GHSR) are expressed in the brain and periphery....
Ghrelin is a peptide that is produced by endocrine cells that are primarily localized in the stomach. Ghrelin receptors (GHSR) are expressed in the brain and periphery. Preclinical and clinical studies support a role for ghrelin in alcohol drinking and seeking. The GHSR has been suggested to be a potential pharmacotherapeutic target for alcohol use disorder (AUD). However, the role of the ghrelin system and its potential modulation by biological sex on binge-like drinking has not been comprehensively investigated. The present study tested six GHSR antagonists in an alcohol binge-like drinking procedure in male and female mice. Systemic administration of the GHSR antagonists JMV2959, PF-5190457, PF-6870961, and HM-04 reduced alcohol intake in both male and female mice. YIL-781 decreased intake in males, and LEAP2 (likely peripherally restricted) did not reduce intake in mice of either sex. We also administered LEAP2 and JMV2959 intracerebroventricularly to investigate whether the effects of GHSR blockade on alcohol intake are mediated by central receptors. The central administration of LEAP2 and JMV2959 decreased alcohol intake, particularly in high-drinking animals. Finally, in a preliminary experiment, an anti-ghrelin vaccine was examined for its potential effect on binge-like drinking and had no effect. In all experiments, there was a lack of meaningful sex differences. These findings suggest that central GHSR mediates binge-like alcohol intake. These data reveal novel pharmacological compounds with translational potential in the treatment of AUD and provide further evidence of the GHSR as a potential treatment target for AUD.
Topics: Female; Mice; Male; Animals; Receptors, Ghrelin; Alcohol Drinking; Ethanol; Alcoholism
PubMed: 37369277
DOI: 10.1016/j.neuropharm.2023.109643 -
The American Journal of Drug and... Nov 2023Previous studies have reviewed the evidence on the increase in alcohol consumption after a terrorist attack. However, an increase does not necessarily imply the... (Meta-Analysis)
Meta-Analysis Review
Previous studies have reviewed the evidence on the increase in alcohol consumption after a terrorist attack. However, an increase does not necessarily imply the presence of an alcohol use disorder. To conduct a systematic and meta-analytic review of the literature on the prevalence of increased alcohol consumption and alcohol use disorders in adult exposed to terrorism. A search of PsycINFO, MEDLINE and PTSDpubs identified 29 studies published up to March 2023 in which 38 adult samples totaling 282,753 persons exposed to terrorism were assessed. Using inverse variance heterogeneity models, pooled prevalence rates of increased alcohol use and alcohol use disorders were calculated. 6% (95% CI [2.9, 9.5]) of the adults exposed to a terrorist attack increased their alcohol consumption. The prevalence of increased alcohol use varied depending on the degree of exposure ( = .006, = .18) and the procedure for measuring increases (= .043, = .37). The prevalence of alcohol use disorders in adults exposed to a terrorist attack was 5.5% (95% CI [3.7, 7.5]), a rate that was not higher than that obtained in the general population and varied depending on the type of alcohol disorder ( = .015, = .30). A relevant number of adults exposed to terrorist attacks will subsequently increase their alcohol consumption, but this increase is not associated with an increase in the prevalence of alcohol use disorders. Effects of terrorism on people's health are potentially widespread, but concerns of excessive alcohol use after terrorist attacks may be unwarranted.
Topics: Adult; Humans; Alcohol Drinking; Alcoholism; Prevalence; Stress Disorders, Post-Traumatic; Terrorism
PubMed: 38011685
DOI: 10.1080/00952990.2023.2275526 -
Annals of Emergency Medicine Jul 2024
Review
Topics: Humans; Substance Withdrawal Syndrome; Ethanol; Alcoholism
PubMed: 38530674
DOI: 10.1016/j.annemergmed.2024.02.016 -
The Journal of Clinical Investigation Jun 2024Alcohol-related harm, a major cause of disease burden globally, affects people along a spectrum of use. When a harmful pattern of drinking is present in the absence of... (Review)
Review
Alcohol-related harm, a major cause of disease burden globally, affects people along a spectrum of use. When a harmful pattern of drinking is present in the absence of significant behavioral pathology, low-intensity brief interventions that provide information about health consequences of continued use provide large health benefits. At the other end of the spectrum, profound behavioral pathology, including continued use despite knowledge of potentially fatal consequences, warrants a medical diagnosis, and treatment is strongly indicated. Available behavioral and pharmacological treatments are supported by scientific evidence but are vastly underutilized. Discovery of additional medications, with a favorable balance of efficacy versus safety and tolerability can improve clinical uptake of treatment, allow personalized treatment, and improve outcomes. Here, we delineate the clinical conditions when pharmacotherapy should be considered in relation to the main diagnostic systems in use and discuss clinical endpoints that represent meaningful clinical benefits. We then review specific developments in three categories of targets that show promise for expanding the treatment toolkit. GPCRs remain the largest category of successful drug targets across contemporary medicine, and several GPCR targets are currently pursued for alcohol-related indications. Endocrine systems are another established category, and several promising targets have emerged for alcohol indications. Finally, immune modulators have revolutionized treatment of multiple medical conditions, and they may also hold potential to produce benefits in patients with alcohol problems.
Topics: Humans; Alcoholism; Alcohol Drinking; Animals
PubMed: 38828724
DOI: 10.1172/JCI172889 -
Scientific Reports Feb 2024This pilot study investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). Participants... (Randomized Controlled Trial)
Randomized Controlled Trial
This pilot study investigated psilocybin-induced changes in neural reactivity to alcohol and emotional cues in patients with alcohol use disorder (AUD). Participants were recruited from a phase II, randomized, double-blind, placebo-controlled clinical trial investigating psilocybin-assisted therapy (PAT) for the treatment of AUD (NCT02061293). Eleven adult patients completed task-based blood oxygen dependent functional magnetic resonance imaging (fMRI) approximately 3 days before and 2 days after receiving 25 mg of psilocybin (n = 5) or 50 mg of diphenhydramine (n = 6). Visual alcohol and emotionally valanced (positive, negative, or neutral) stimuli were presented in block design. Across both alcohol and emotional cues, psilocybin increased activity in the medial and lateral prefrontal cortex (PFC) and left caudate, and decreased activity in the insular, motor, temporal, parietal, and occipital cortices, and cerebellum. Unique to negative cues, psilocybin increased supramarginal gyrus activity; unique to positive cues, psilocybin increased right hippocampus activity and decreased left hippocampus activity. Greater PFC and caudate engagement and concomitant insula, motor, and cerebellar disengagement suggests enhanced goal-directed action, improved emotional regulation, and diminished craving. The robust changes in brain activity observed in this pilot study warrant larger neuroimaging studies to elucidate neural mechanisms of PAT.Trial registration: NCT02061293.
Topics: Adult; Humans; Alcoholism; Psilocybin; Pilot Projects; Magnetic Resonance Imaging; Brain; Cues; Ethanol
PubMed: 38326432
DOI: 10.1038/s41598-024-52967-8 -
Clinical Therapeutics Dec 2023This review will provide an overview of alcohol use and alcohol associated liver disease (ALD) prior to the coronavirus disease 2019 (COVID-19) pandemic and the impact... (Review)
Review
PURPOSE
This review will provide an overview of alcohol use and alcohol associated liver disease (ALD) prior to the coronavirus disease 2019 (COVID-19) pandemic and the impact of the pandemic on alcohol use and ALD. Furthermore, this review will explore strategies to mitigate the growing disease burden of AUD and ALD.
METHODS
A search using PubMed was performed for articles on topics related to alcohol use, ALD, and COVID-19. The literature was reviewed and pertinent sources were used for this narrative review.
FINDINGS
In the United States (US), excessive alcohol use is the third leading cause of preventable death. Prior to the COVID-19 pandemic, the increasing prevalence of alcohol use disorder (AUD) and ALD in the US had already constituted a public health crisis given the association between alcohol misuse, AUD, and ALD with significant medical, economic, and societal burdens. The COVID-19 pandemic led to increased alcohol consumption and downstream consequences, including increased prevalence of AUD, ALD, ALD-related hospitalization and death, and liver transplantation for ALD.
IMPLICATIONS
There is a critical need for additional, multi-pronged interventions to mitigate the mortality and morbidity linked to ALD.
Topics: Humans; Pandemics; COVID-19; Liver Diseases, Alcoholic; Liver Transplantation; Ethanol; Alcoholism
PubMed: 37758533
DOI: 10.1016/j.clinthera.2023.08.019 -
Pharmacology, Biochemistry, and Behavior Feb 2024Alcohol use disorder is a chronic recurrent encephalopathy, and its pathogenesis has not been fully understood. Among possible explanations, neuroinflammation caused by... (Review)
Review
BACKGROUND
Alcohol use disorder is a chronic recurrent encephalopathy, and its pathogenesis has not been fully understood. Among possible explanations, neuroinflammation caused by the disorders of brain central immune signaling has been identified as one possible mechanism of alcohol use disorder. As the basic components of cells and important bioactive molecules, sphingolipids are essential in regulating many cellular activities. Recent studies have shown that sphingolipids-mediated neuroinflammation may be involved in the development of alcohol use disorder.
METHODS
PubMed databases were searched for literature on sphingolipids and alcohol use disorder (alcohol abuse, alcohol addiction, alcohol dependence, and alcohol misuse) including evidence of the relationship between sphingolipids-mediated neuroinflammation and alcohol use disorder (formation, withdrawal, treatment).
RESULTS
Disorders of sphingolipid metabolism, including the different types of sphingolipids and regulatory enzyme activity, have been found in patients with alcohol use disorder as well as animal models, which in turn cause neuro-inflammation in the central nervous system. Thus, these disorders may also be an important mechanism in the development of alcohol use disorder in patients. In addition, different sphingolipids may have different or even reverse effects on alcohol use disorder.
CONCLUSIONS
The sphingolipids-mediated neuroinflammation plays an important role in the development of alcohol use disorder. This review proposes a potential approach to prevent and treat alcohol use disorders by manipulating sphingolipid metabolism.
Topics: Animals; Humans; Sphingolipids; Alcoholism; Neuroinflammatory Diseases; Central Nervous System; Alcohol Drinking
PubMed: 38128765
DOI: 10.1016/j.pbb.2023.173695 -
Hepatology Communications Feb 2024Alcohol-associated liver disease is a common and severe sequela of excessive alcohol use; effective treatment requires attention to both liver disease and underlying...
Alcohol-associated liver disease is a common and severe sequela of excessive alcohol use; effective treatment requires attention to both liver disease and underlying alcohol use disorder (AUD). Alcohol withdrawal syndrome (AWS) can be dangerous, is a common barrier to AUD recovery, and may complicate inpatient admissions for liver-related complications. Hepatologists can address these comorbid conditions by learning to accurately stage alcohol-associated liver disease, identify AUD using standardized screening tools (eg, Alcohol Use Disorder Identification Test), and assess risk for and symptoms of AWS. Depending on the severity, alcohol withdrawal often merits admission to a monitored setting, where symptom-triggered administration of benzodiazepines based on standardized scoring protocols is often the most effective approach to management. For patients with severe liver disease, selection of benzodiazepines with less dependence on hepatic metabolism (eg, lorazepam) is advisable. Severe alcohol withdrawal often requires a "front-loaded" approach with higher dosing, as well as intensive monitoring. Distinguishing between alcohol withdrawal delirium and HE is important, though it can be difficult, and can be guided by differentiating clinical characteristics, including time to onset and activity level. There is little data on the use of adjuvant medications, including anticonvulsants, dexmedetomidine, or propofol, in this patient population. Beyond the treatment of AWS, inpatient admission and outpatient hepatology visits offer opportunities to engage in planning for ongoing management of AUD, including initiation of medications for AUD and referral to additional recovery supports. Hepatologists trained to identify AUD, alcohol-associated liver disease, and risk for AWS can proactively address these issues, ensuring that patients' AWS is managed safely and effectively and supporting planning for long-term recovery.
Topics: Humans; Alcoholism; Substance Withdrawal Syndrome; Liver Diseases, Alcoholic; Benzodiazepines; Cognition
PubMed: 38251886
DOI: 10.1097/HC9.0000000000000372 -
Pancreatology : Official Journal of the... Sep 2023Complications in chronic pancreatitis (CP) can be grouped in inflammatory (ICC) and fibrotic (FCC) clusters and pancreatic insufficiency cluster (PIC). However, the...
BACKGROUND
Complications in chronic pancreatitis (CP) can be grouped in inflammatory (ICC) and fibrotic (FCC) clusters and pancreatic insufficiency cluster (PIC). However, the association between etiological risk factors and the development of complication clusters remains obscure. In this study, the impact of the etiology and disease duration on disease onset and development of complications was investigated.
METHODS
This cross-sectional study recruited patients with CP from Mannheim/Germany (n = 870), Gieβen/Germany (n = 100) und Donetsk/Ukraine (n = 104). Etiological risk factors, disease stage, age at disease onset, complications, need for hospitalization and surgery were noted.
RESULTS
In 1074 patients diagnosed with CP, main risk factors were alcohol and nicotine abuse. An earlier onset of the disease was observed upon nicotine abuse (-4.0 years). Alcohol abuse was only associated with an earlier onset of the definite stage of CP. Alcohol abuse was the major risk factor for the development of ICC (p < 0.0001, multiple regression modeling). Abstinence of alcohol reduced ICC, whereas abstinence of nicotine showed no association. PIC correlated with efferent duct abnormalities and the disease duration. In contrast, FCC was mainly dependent on the disease duration (p < 0.0001; t-test). The presence of any complication cluster correlated with the need for surgery (p < 0.01; X-test). However, only ICC correlated with a prolonged hospital stay (p < 0.05; t-test).
CONCLUSIONS
ICC is mainly dependent on alcohol abuse. In contrast, FCC and PIC are mainly dependent on the disease duration. The etiology and disease duration can be used as predictors of the course of disease to provide individual treatment and surveillance strategies.
Topics: Humans; Alcoholism; Nicotine; Cross-Sectional Studies; Pancreatitis, Chronic; Risk Factors; Exocrine Pancreatic Insufficiency
PubMed: 37393150
DOI: 10.1016/j.pan.2023.06.015 -
Drug and Alcohol Review Nov 2023People who enter custody have complex health issues and comorbidities may include alcohol use disorders. We investigated clinical service provision and comorbidities... (Review)
Review
INTRODUCTION
People who enter custody have complex health issues and comorbidities may include alcohol use disorders. We investigated clinical service provision and comorbidities recorded among individuals with a likely alcohol withdrawal syndrome within prison in New South Wales, Australia.
METHODS
For this clinical case series review, electronic medical data were used to identify 50 people entering custody between August and November 2018 who likely had a treated alcohol withdrawal syndrome. We aimed for a 3:2 ratio of men and women, and a 1:1 ratio of Aboriginal and non-Aboriginal individuals. Data were extracted using a purposefully designed tool which included current alcohol withdrawal management, comorbidities and alcohol relapse prevention approaches used or recommended.
RESULTS
Thirty-eight men and 12 women, of whom 22 were Aboriginal, were included. Twenty-nine individuals (58%) reported a history of medical comorbidities. Thirty-five (70%) reported using other substances and over half (60%) had a diagnosis of mental health disorders. Fourteen (28%) individuals had a record of receiving brief intervention and five (10%) of motivational interviewing. Twenty-three individuals (46%) were referred to and seen by drug and alcohol clinicians. Only seven (14%) of the sample had pre-release community care plans.
DISCUSSION AND CONCLUSIONS
Individuals treated for an alcohol withdrawal syndrome in New South Wales prisons have a high prevalence of medical comorbidities and other substance use. Clinical interventions focused on alcohol withdrawal management, and relapse prevention interventions were not recorded for most individuals. Service innovation and expansion are needed to increase the provision of post-withdrawal management.
Topics: Female; Humans; Male; Alcoholism; Australia; Delivery of Health Care; New South Wales; Prisons; Secondary Prevention; Substance Withdrawal Syndrome
PubMed: 37608431
DOI: 10.1111/dar.13741