Severe alcohol withdrawal syndrome (SAWS) can lead to significant morbidity and mortality. The Prediction of Alcohol Withdrawal Severity Scale (PAWSS) has been validated in general acute care environments, but its efficacy in withdrawal management settings remains underexplored. This study aimed to assess the utility of a modified PAWSS and identify appropriate cutoff scores in a community withdrawal management setting in Vancouver, Canada.

From October 2019 to September 2022, we reviewed charts at Vancouver Detox Centre. Modified PAWSS versions replaced question 9 on the original PAWSS with: (i) breath analysis readings; (ii) alcohol consumption in the previous 24 h; and (iii) clinical assessments. We performed receiver operating characteristic analysis and used Youden's index to determine modified PAWSS' diagnostic accuracy against SAWS presentation, defined by a score of 15 or greater on the Clinical Institute Withdrawal Assessment Alcohol, Revised, seizures or delirium tremens and/or benzodiazepine administration.

Among 228 individuals (165 male, 63 female), 175 (75%) met SAWS criteria during admission. For breath analysis readings, an optimal PAWSS cutoff score had 55% sensitivity (95% confidence interval [CI] 46%-63%) and 74% specificity (95% CI 54%-87%). For alcohol consumption in the last 24 h, a cutoff score of 7 had 44% sensitivity (95% CI 36%-51%) and 85% specificity (95% CI 70%-93%). For clinical assessment, a cutoff score of 6 had 53% sensitivity (95% CI 45%-61%) and 71% specificity (95% CI 58%-85%).

Within a community withdrawal setting, the prevalence of SAWS was high, rendering the modified PAWSS less valuable. Although higher cutoff scores improved specificity, poor sensitivity hindered identification of low-risk SAWS individuals.

Substance Use Disorders (SUDs) involve diminished control, risky use, impaired social interactions, and physical dependence. Despite their global prevalence and burden, treatment options remain limited. Ketamine (KET), an NMDA receptor antagonist, may aid SUD treatment by modulating glutamatergic neurotransmission. This systematic review evaluates KET's role in SUD treatment.

This review surveyed three databases until June 2024, including 14 studies with 551 participants.

Among the 14 studies, 6 focused on alcohol, 3 on cocaine, 4 on opioids, and 1 on cannabis. Seven studies (50 %) combined KET with psychotherapy, while seven (50 %) focused solely on KET's pharmacological effects. KET dose ranges varied from 0.11 mg/kg to 2.0 mg/kg and study primary endpoints ranged from less than a day to two years. The results of the included studies demonstrated KET's efficacy across various SUDs. In Alcohol Use Disorder (AUD), KET reduced withdrawal symptoms and benzodiazepine requirements. In Cocaine Use Disorder (CUD), KET decreased craving and increased abstinence rates. In Opioid Use Disorder (OUD), high-dose KET psychotherapy (KPT) improved abstinence and reduced craving. In Cannabis Use Disorder (CNUD), KET reduced weekly use and increased abstinence confidence.

Conclusion: While preliminary studies suggest that KET may have short-term benefits in treating SUDs, the evidence remains limited by small sample sizes and a lack of randomized trials. Further research with larger, well-controlled studies is needed to determine optimal dosing, clarify mechanisms of action, and assess long-term efficacy and potential risks, including abuse liability, before broader clinical implementation can be recommended.

Older adults with acute mental health concerns represent a large and growing population presenting to emergency departments (EDs). An organized approach to seniors experiencing a mental health crisis, grounded in a life course perspective, is essential. A structured approach to suicide risk assessment is a key part of ED practice. Mania, psychosis, anxiety, trauma, substance use, and the neuropsychiatric complications of Parkinson's disease are described in this article.

Alcohol dependence (AD) confers susceptibility to distressing withdrawal symptoms that often lead to relapse. While neuroadaptation during withdrawal influences symptoms, the genetic factors behind it have not been thoroughly investigated. We utilized propensity score matching and investigated connections between AD, OXT rs6133010, and withdrawal symptoms to address confounding variables. By elucidating the OXT rs6133010-AD interaction, we aim to gain insights into alcohol withdrawal variability and contribute to personalized treatment approaches.

A cross-sectional study design was employed involving a total of 389 AD patients and 184 healthy controls who were genotyped for the OXT rs6133010 polymorphism. Psychiatric symptoms were evaluated using standardized scales during early withdrawal. Propensity score matching mitigated age and education differences.

A two-way ANOVA demonstrated a significant AD x OXT rs6133010 interaction effect on hostility and anxiety. Further analysis revealed that the regulatory impact of OXT rs6133010 was exclusively in AD patients. Specifically, AD patients with the AA homozygote showed robust protection against hostility and anxiety. Path analysis unveiled the underlying mechanism of OXT symptom regulation.

This study presents novel evidence that OXT rs6133010 specifically modulates psychiatric symptoms in AD. The G allele may heighten hostility and anxiety vulnerability during alcohol withdrawal. These findings emphasize considering environmental factors when studying and utilizing oxytocin therapeutically. Additionally, OXT may not directly act as an anxiolytic but instead regulates anxiety by modulating hostility.

Caffeine Use Disorder (CUD) is not currently recognized as a formal diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). However, recent studies within the DSM-5 context have explored this issue. Also, this disorder is closely associated with caffeine withdrawal symptoms, which are formally recognized as a diagnosis in the DSM-5. Additionally, there is limited evidence regarding the connection between caffeine-related issues and psychiatric symptoms. The main aim of the present study was to determine the network structure of CUD and caffeine withdrawal symptoms among the general population. Also, the bridge symptoms among CUD, psychiatric symptoms, and caffeine withdrawal have been estimated.

Participants were 1228 adults (50.3% females, Mean age (x̄±sd) 35.49 ± 11.70 years) who completed Caffeine Use Disorder Questionnaire (CUDQ), Caffeine Withdrawal Symptoms Questionnaire (CWSQ), and Symptom Checklist-25 (SCL-25). All estimations were conducted according to the Gaussian Graphical Model.

"Excessive consumption" and "role obligations" were central symptoms in the CUD network. Difficulty in concentration was the most central node in the caffeine withdrawal network. Also, the obsessive-compulsive symptom emerged as a central and highly influential node in the relationship between caffeine-related nodes and psychiatric symptoms.

Mental health providers should target these specific symptoms in clinical interventions to mitigate caffeine-related problems among individuals in the general population effectively.

Although safety and effectiveness of medications for alcohol use disorder (AUD) are well established for adults, literature on these medications in pregnancy is limited. Given known adverse effects of untreated AUD during pregnancy, clinicians and researchers have recently begun to call for reconsidering use of medications for AUD in pregnancy. Thus, we sought to estimate the proportion of birthing people with an alcohol-related diagnosis who received a prescription for medication related to AUD treatment.

Data were from Meritive MarketScan, a national private insurance claims database. The study cohort included birthing people aged 25-50 who gave birth to a singleton in the United States between 2006 and 2019 and were matched with an infant. Variables included an alcohol-related diagnosis within a year of birth and receiving a prescription for a medication related to AUD treatment. We calculated proportions with alcohol-related diagnoses who received any AUD medication and each medication type.

Of 1,432,979 birthing person-infant dyads, 2517 (0.18%) had an alcohol-related diagnosis. Of those with an alcohol-related diagnosis, 8.70% (n = 219) received any medication. The most common was gabapentin (4.69%, n = 118), with benzodiazepines for withdrawal as the second most common (2.19%, n = 55). Approximately 2% received naltrexone (1.91%, n = 48) and/or disulfiram (1.39%, n = 35); 0.56% (n = 14) received acamprosate. No one with an alcohol-related diagnosis received phenobarbital. Almost all medications were received postpartum.

Very few pregnant/postpartum people with alcohol-related diagnoses are prescribed medications related to AUD treatment. Research is needed to examine whether benefits of these medications during pregnancy outweigh harms.

Acute encephalopathy is a common presenting symptom in the emergency room and complicates many hospital and intensive care unit admissions. The evaluation of patients with encephalopathy poses several challenges: limited history and examination due to the patient's mental status, broad differential diagnosis of systemic and neurologic etiologies, low yield of neurodiagnostic testing due to the high base rate of systemic causes, and the importance of identifying less common neurologic causes of encephalopathy that can be life-threatening if not identified and treated. This article discusses the differential diagnosis of acute encephalopathy, presents an approach to the history and examination in a patient with encephalopathy, reviews the literature on the yield of neurodiagnostic testing in this population, and provides a diagnostic framework for the evaluation of patients with altered mental status.

Anxiety is a part of the human condition and has been managed by psychoactive substances for centuries. The current medical need and societal demand for anxiolytic medicines has not abated. The present overview provides a brief historical introduction to the discovery of modern age anxiolytics that include the benzodiazepines together with a discussion of the continuing medical need for new antianxiety medications. The paper also discusses the use and impact of behavioral pharmacology in the preclinical development of anxiolytics. The review then highlights the diversity of mechanisms for creating a new generation of anxiolytics through mechanisms beyond the potentiation of GABAA receptors and the blockade of monoamine uptake. A discussion then follows on the behavioral specificity of action of anxiolytics that includes the concept of creating an anxioselective drug, one that targets anxiety without producing untoward effects that include sedation and dependence. The use of anxiolytics in the treatment of other conditions such as substance use disorder is also briefly reviewed. Finally, a brief summary of the current status of anxiolytic drug development is provided. The review concludes with the idea that despite a host of anxiolytic drugs, the lack of efficacy in some patients and the side-effects and safety issues associated with some of these medications demands alternative medicines. Current preclinical and clinical research is ongoing with the goal of identifying such compounds.

Alcohol withdrawal is a common reason for admission to acute care hospitals. Prescription of medications for alcohol-use disorder (AUD) and close outpatient follow-up are commonly recommended, but few studies report their effects on postdischarge outcomes.

The objective of this study is to evaluate the effects of medications for AUD and follow-up appointments on readmission and abstinence.

This retrospective cohort study evaluated veterans admitted for alcohol withdrawal to medical services at 19 Veteran Health Administration hospitals between October 1, 2018 and September 30, 2019. Factors associated with all-cause 30-day readmission and 6-month abstinence were examined using logistic regression.

Of the 594 patients included in this study, 296 (50.7%) were prescribed medications for AUD at discharge and 459 (78.5%) were discharged with follow-up appointments, including 251 (42.8%) with a substance-use clinic appointment, 191 (32.9%) with a substance-use program appointment, and 73 (12.5%) discharged to a residential program. All-cause 30-day readmission occurred for 150 patients (25.5%) and 103 (17.8%) remained abstinent at 6 months. Medications for AUD and outpatient discharge appointments were not associated with readmission or abstinence. Discharge to residential treatment program was associated with reduced 30-day readmission (adjusted odds ratio [AOR]: 0.39, 95% confidence interval [95% CI]: 0.18-0.82) and improved abstinence (AOR: 2.50, 95% CI: 1.33-4.73).

Readmission and return to heavy drinking are common for patients discharged for alcohol withdrawal. Medications for AUD were not associated with improved outcomes. The only intervention at the time of discharge that improved outcomes was discharge to residential treatment program, which was associated with decreased readmission and improved abstinence.

Psychedelics have recently (re)emerged as therapeutics of high potential for multiple mental health conditions, including substance use disorders (SUDs). Despite early mid-20th century anecdotal reports and pilot studies demonstrating the possibility of these substances in efficaciously treating conditions such as alcohol and opioid use disorders, legal restrictions and social stigma have historically hindered further research into this area. Nevertheless, concurrent with the rise in SUDs and other mental health conditions, researchers have again turned their attention to these compounds, searching for differing pharmacological targets as well as more holistic treatments that might increase patient adherence and efficacy. The aim of this review is to examine the emerging evidence-based data with regards to the therapeutic treatment of SUDs with the psychedelic compounds psilocybin, ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), ayahuasca, ibogaine and peyote.

Alcohol withdrawal can occur following the abrupt cessation or marked reduction of alcohol use in a person with alcohol dependence. This article provides an overview of the assessment and management of acute unplanned alcohol withdrawal, and discusses the crucial role of nurses in addressing this complex condition. It outlines the pathophysiology, signs and symptoms of alcohol withdrawal and explains the need for a multifaceted approach to its management, often involving a combination of pharmacological treatment and supportive care. The article aims to equip nurses with the knowledge and skills necessary to improve outcomes for people experiencing alcohol withdrawal.

Delirium is a common complication in acute stroke patients, occurring in 15-35% of all stroke unit admissions and is associated with prolonged hospital stay and a poor post-stroke prognosis. Managing delirium in acute stroke patients necessitates an intensive and multiprofessional therapeutic approach, placing a significant burden on healthcare staff. However, dedicated practical recommendations for delirium management developed for the population of acute stroke patients are lacking. For this purpose, the Austrian Stroke Society, in cooperation with the Austrian Society of Neurology, the Austrian Society of Neurorehabilitation, and the Austrian Society of Psychiatry, Psychotherapy, and Psychosomatics has formulated an evidence-based position paper addressing the management of delirium in acute stroke patients. The paper outlines practical recommendations on the three pillars of care in stroke patients with delirium: (a) Key aspects of delirium prevention including stroke-specific delirium risk factors and delirium prediction scores are described. Moreover, a non-pharmacological delirium prevention bundle is presented. (b) The paper provides recommendations on timing and frequency of delirium screening to ensure early diagnosis of delirium in acute stroke patients. Moreover, it reports on the use of different delirium screening tools in stroke populations. (c) An overview of non-pharmacological and pharmacological treatment strategies in patients with delirium and acute stroke is presented and summarized as key recommendation statements.

This study investigated the effects of zonisamide treatment on cerebellar tissues in an experimental alcohol addiction (AA) model and its potential mechanisms of action, particularly regarding apoptotic protease activating factor-1 (APAF-1) and tumor necrosis factor-alpha (TNF-α) expression. Thirty rats were divided into three groups: sham, ethanol (EtOH), and EtOH + zonisamide. AA was induced by administering 6 cc of EtOH orally every 8 h for 4 days. Zonisamide (100 mg/kg) was given to rats once daily before EtOH administration. Motor defects were evaluated using an open field maze. Serum TNF-α levels were measured from blood samples. Cerebellar sections were processed for histological examination and immunostained for APAF-1 and TNF-α. Protein interaction networks were constructed using Cytoscape, and functional annotations were performed with ShinyGO (version 0.80) software. The traveled area in the EtOH group was significantly reduced compared to the sham group (p = 0.0005). Rats in the EtOH + zonisamide group covered a larger area, with zonisamide treatment significantly improving locomotor ability compared to the EtOH group (p = 0.0463). Serum TNF-α levels were significantly elevated in the EtOH group compared to the sham group (p < 0.0001) and were significantly decreased in the EtOH + zonisamide group compared to the EtOH group (p = 0.0309). Regular cerebellar histological layers were observed in the sham group, while EtOH induction caused loss of cerebellar tissue integrity, neuronal degeneration, vascular dilatation and congestion, reduced myelin density, and neuropils in the EtOH group. Zonisamide treatment improved these pathologies, enhancing myelination and neuropil formation. Negative APAF-1 and TNF-α expressions were observed across cerebellar layers in the sham group. Due to EtOH toxicity, APAF-1 and TNF-α expression were upregulated in the EtOH group compared to the sham group (p < 0.001 for both). Zonisamide treatment downregulated these protein expressions in the EtOH + zonisamide group compared to the EtOH group (p < 0.001 and p = 0.0087, respectively). APAF-1 was primarily associated with AA through antifolate resistance, endopeptidases, and the interleukin-1 pathway, while TNF-α was predominantly enriched in infections and choline-binding, indicating zonisamide's impact on immune and inflammatory pathways. In conclusion, zonisamide treatment significantly mitigated ethanol-induced cerebellar damage and inflammation in an AA model. Zonisamide improved locomotor function and reduced serum TNF-α levels, as well as APAF-1 and TNF-α expression in cerebellar tissues. These findings suggest that zonisamide exerts its protective effects by modulating immune and inflammatory pathways, thereby preserving cerebellar integrity and function.

Alcohol use disorder (AUD) is a significant risk factor, accounting for approximately 13% of all deaths in the US. AUD not only destroys families but also causes economic losses due to reduced productivity, absenteeism, and healthcare expenses. Statistics revealing the sustained number of individuals affected by AUD over the years underscore the need for further understanding of the underlying pathophysiology to advance novel therapeutic strategies. Previous research has implicated the limbic brain regions N-methyl-D-aspartate glutamate receptors (NMDAR) in the emotional and behavioral effects of AUD. Given that aerobic exercise can modulate NMDAR activity and sensitivity to alcohol, this review presents a summary of clinical and basic science studies on NMDAR levels induced by alcohol consumption, as well as acute and protracted withdrawal, highlighting the potential role of aerobic exercise as an adjunctive therapy for AUD. Based on our findings, the utility of exercise in the modulation of reward-linked receptors and AUD may be mediated by its effects on NMDA signaling. These data support further consideration of the potential of aerobic exercise as a promising adjunctive therapy for AUD.

Background: Delirium Tremens (DT) is known to be a serious complication of alcohol withdrawal syndrome (AWS). Neurotransmitter abnormalities, inflammation, and increased permeability are associated with the pathogenesis of AWS and DT. However, the biomarkers of these conditions are still poorly understood. Methods: In this work, biochemical, hematologic, inflammatory, and gut permeability biomarkers were investigated in the following three groups: healthy controls (n = 75), severe AWS patients with DT (n = 28), and mild/moderate AWS without DT (n = 97). Blood sampling was performed after resolution of the acute condition (on 5 ± 1 day after admission) to collect clinical information from patients and to investigate associations with clinical scales. Biomarker analysis was performed using automated analyzers and ELISA. Inflammatory biomarkers included the erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), and platelet-to-lymphocyte ratio (PLR). Results: Among the biochemical biomarkers, only glucose, total cholesterol, and alanine aminotransferase (ALT) changed significantly in the analyzed groups. A multiple regression analysis showed that age and ALT were independent predictors of the CIWA-Ar score. Hematologic biomarker analysis showed an increased white blood cell count, and the elevated size and greater size variability of red blood cells and platelets (MCV, RDWc, and PDWc) in two groups of patients. Gut permeability biomarkers (FABP2, LBP, and zonulin) did not change, but were associated with comorbid pathologies (alcohol liver disease and pancreatitis). The increase in inflammatory biomarkers (ESR and PLR) was more evident in AWS patients with DT. Cluster analysis confirmed the existence of a subgroup of patients with evidence of high inflammation, and such a subgroup was more frequent in DT patients. Conclusions: These findings contribute to the understanding of biomarker variability in AWS patients with and without DT and support the heterogeneity of patients by the level of inflammation.

Delirium tremens (DT) is a severe condition resulting from alcohol withdrawal. This review highlights the challenges in diagnosing and managing DT and emphasizes the importance of early recognition and intervention to prevent complications and ensure optimal patient outcomes. The discussion of the pathophysiology of DT, focusing on the neurochemical imbalances involving the neurotransmitters gamma-aminobutyric acid and glutamate, explains how chronic alcohol dependence leads to these imbalances and contributes to the hyperexcitability seen in DT. The management of DT involves ensuring patient safety and alleviating symptoms, primarily through pharmacological approaches, such as benzodiazepines. Closely monitoring vital signs and electrolyte imbalances is necessary due to autonomic dysregulation associated with DT. The mention of the potential complexity of DT when coexisting with other conditions emphasizes the need for additional research to advance comprehension, identify predictive factors, and enhance its management.

New approaches for the treatment of alcohol dependence (AD) may improve patient outcomes. Substitution maintenance therapy is one of the most effective treatment options for opioid and nicotine use disorders. So far, there has been little attention to substitution therapy for the treatment of AD. Here, we explain the mechanistic foundations of alcohol substitution maintenance therapy. Alcohol has many primary targets in the brain (and other organs) and the physical interaction of ethanol molecules with these specific ethanol-sensitive sites on a variety of ionotropic receptors (e.g. GABA-A, NMDA, and nicotinic acetylcholine (nACh) receptors) and ion channels provides the rationale for substitution. As such, a variety of compounds can interact with those ethanol-sensitive sites and can thus substitute for some of the effects of alcohol. For some of these compounds, alcohol discrimination studies have shown their substitution potential. Accordingly, potential substitution treatments include agonists acting at GABA receptors such as sodium oxybate, baclofen and benzodiazepines, NMDA receptor antagonists such as ketamine and memantine, or nAChRs agonists such as varenicline. All these compounds are already approved for other indications and we present clinical evidence for these drugs in the treatment of alcohol withdrawal syndrome (AWS) and in the long-term treatment of AD, and outline future steps for their acceptance as substitution treatment in AD. Finally, we discuss the substitution approach of managed alcohol programs for the most severely affected homeless populations. Results showed that sodium oxybate is probably the closest to a substitution therapy for AD and is already approved for the treatment of AWS and in the long-term treatment of AD in some countries. In conclusion, we argue that better AD treatment can be provided if substitution maintenance treatments for alcohol are implemented at a similar scale as for opioid and nicotine use disorder.

To investigate variations in intended utilization in cases of an acute psychotic episode, an alcohol related or depressive disorder depending on different case characteristics.

A telephone survey with case vignettes was conducted (N=1,200). Vignettes varied in terms of urgency of symptoms, daytime, sex of the afflicted person and age/mental disorder. The respondents were asked to indicate whom they would contact first in the described case.

Outpatient physicians were named most frequently as the first point of contact (61.1%) while only 6.5% of the respondents named emergency medicine including the medical on call service (8.1% in high urgency cases, i. e. emergencies that did not tolerate any delay). Intended utilization varied by urgency and age/mental illness.

More Information about the need to seek medical help immediately in cases of mental illnesses with high urgency should be provided.

Delirium is an acute reversible neuropsychiatric syndrome caused by multiple factors. It is associated with many adverse clinical outcomes including cognitive impairment, functional decline, prolonged hospitalization, and increased nursing service. The prevalence of delirium was high in department of cardiology, geriatric, and intensive care unit of hospital. With the increase in the aged population, further increases in delirium seem likely. However, it remains poorly recognized in the clinical practice. This article comprehensively discusses the latest research perspectives on the epidemiological data, risk factors, preventive interventions, overlapping symptoms, and clinical measures of delirium, including specific measures to manage delirium in clinical real-world situations. This article helps readers improve their knowledge and understanding of delirium and helps clinicians quickly identify and implement timely therapeutic measures to address various delirium subtypes that occur in the clinical settings to ensure patients are treated as aggressively as possible.

Background: A better understanding of factors associated with not ready to stop using substances may inform provider engagement with clients who have an unmet treatment need.Objectives: This study explores how treatment barriers, the number of SUD symptoms, and types of substances used are associated with not ready to stop using substances among adults with an unmet treatment need.Methods: The data came from the 2015-2019 National Survey on Drug Use and Health. Eligible adults met DSM-IV criteria for substance abuse and dependence and reported an unmet need for treatment. Among our sample (N = 1,017), a majority self-identified as male (weighted 59.3%). We employed multivariable logistic regression to examine individual-level factors associated with not being ready to stop using substances.Results: About 38% of the respondents reported that they were not ready to stop using substances. Reporting access barriers (aOR = 0.44, 95% CI: 0.29, 0.68) and attitudinal barriers (aOR = 0.47, 95% CI: 0.28, 0.80) was associated with a lower odds of not ready to stop using. Each additional increase in SUD symptoms was associated with 23% higher odds of not being ready to stop using (aOR = 1.22, 95% CI: 1.12, 1.34). Having a diagnosis of alcohol and/or marijuana abuse or dependence was associated with higher odds of not being ready to stop using when compared to respondents without these diagnoses (aOR = 2.13, 95% CI: 1.33, 3.40; aOR = 1.82 95% CI: 1.11, 2.99).Conclusion: Not ready to stop using substances may be impacted by the type of SUD, number of SUD symptoms, and certain barriers like access and attitude to care.

Several β-lactam derivatives upregulate astrocytic glutamate transporter type 1expression and are known to improve measures in models of mood and alcohol use disorders (AUD) through normalizing glutamatergic states. However, long-term, and high doses of β-lactams may cause adverse side effects for treating mood disorders and AUD. Studies suggest that MC-100093, a novel β-lactam lacking antimicrobial activity, rescues GLT1 expression. Thus, we sought to investigate whether MC-100093 improves affective behaviors and reduces voluntary ethanol drinking. We intraperitoneally administered MC-100093 (50 mg/kg) or vehicle once per day to C57BL/6J male and female mice (8-10 weeks old) over 6 days. We employed the open field test and the elevated plus maze to examine the effect of MC-100093 on anxiety-like behaviors. We assayed MC-100093's effects on depressive-like behaviors using the tail suspension and forced swim tests. Next, utilizing a separate cohort of male and female C57BL6 mice, we assessed the effects MC100093 treatment on voluntary ethanol drinking utilizing the 2-bottle choice continuous access drinking paradigm. After screening and selecting high-drinking mice, we systematically administered MC-100093 (50 mg/kg) or vehicle to the high-drinking mice over 6 days. Overall, we found that MC-100093 treatment resulted in sex-specific pharmacological effects with female mice displaying reduced innate depressive-like behaviors during the tail suspension and force swim testing juxtaposed with male treated mice who displayed no changes in tail suspension and a paradoxical increased depressive-like behavior during the forced swim testing. Additionally, we found that MC100093 treatment reduced female preference for 10% EtOH during the 2-bottle choice continuous access drinking with no effects of MC100093 treatment detected in male mice. Overall, this data suggests sex-specific regulation of innate depressive-like behavior and voluntary EtOH drinking by MC100093 treatment. Western blot analysis of the medial prefrontal cortex and hippocampus revealed no changes in male or female GLT1 protein abundance relative to GAPDH.

Ethanol remains one of the most frequently abused agents by adolescents, exceeding all others except for vaping nicotine, and use is rising. With increased ethanol use comes a greater risk for dependence and potential for alcohol withdrawal syndromes (AWS). Pediatric AWS is extremely rare and poorly characterized in the literature. Pediatric acute care practitioners may have limited exposure to AWS. We report the case of a 16-year-old male with a history of polysubstance abuse who presented with mild AWS and progressed rapidly to delirium tremens. His withdrawal was initially refractory to high dose benzodiazepine therapy but responded well to phenobarbital. This case highlights how rapidly and dangerously AWS can progress if not aggressively treated. Given the rise in adolescent alcohol use and potential for life threatening symptoms, practitioners, especially in acute care specialties such as emergency medicine, critical care, and hospital medicine, would benefit from additional familiarity with AWS diagnoses and management strategies.

Despite the teratogenic effects of alcohol, little is known about the safety of pharmacotherapies such as acamprosate for the treatment of alcohol use disorders in pregnancy. The aims of this study were to investigate, in a mouse model, the effects of maternally administered acamprosate on maternal and neonatal health, offspring neurodevelopment and behaviour, as well as examine whether acamprosate reduces the neurological harm associated with alcohol consumption in pregnancy.

Dams were randomly allocated to one of four treatment groups: (i) control (water), (ii) acamprosate (1.6 g/L), (iii) alcohol (5% v/v) or (iv) acamprosate and alcohol (1.6 g/L; 5% v/v ethanol) and exposed from 2-weeks pre-pregnancy until postpartum day 7. Gestational outcomes including litter size and sex ratio were assessed, in addition to early-life markers of neurodevelopment. At 8 weeks of age, motor coordination, anxiety, locomotion, and memory of the adult offspring were also examined.

Exposure to acamprosate did not affect maternal and birth outcomes (mating success, gestational weight gain, litter size, sex ratio), neonatal outcomes (head and body length, postnatal weight) or neurodevelopmental markers (righting reflex and negative geotaxis). Acamprosate exposure did not affect offspring motor control, locomotion or anxiety, however the effects on short-term memory remain uncertain. Prenatal alcohol exposed offspring exhibited various alterations, such as lower postnatal weight, smaller head (p = 0.04) and body lengths (p = 0.046) at postnatal day 70 (males only), increased negative geotaxis speed (p = 0.03), an increased time spent in the inner zone of the open field (p = 0.02). Acamprosate mitigated the effects of alcohol for negative geotaxis at postnatal day 7 (p = 0.01) and female offspring weight at postnatal day 70 (p = 0.03).

Overall, we show that prenatal acamprosate exposure was not associated with poor maternal or neonatal health outcomes or impaired neurodevelopment and behaviour. However, acamprosate's effects on short-term memory remain uncertain. We present preliminary evidence to suggest acamprosate displayed some neuroprotective effects against damage caused by in utero alcohol exposure.

Alcohol is one of the most widely consumed psychoactive drugs globally. Hazardous drinking, defined by quantity and frequency of consumption, is associated with acute and chronic morbidity. Alcohol use disorders (AUDs) are psychiatric syndromes characterized by impaired control over drinking and other symptoms. Contemporary aetiological perspectives on AUDs apply a biopsychosocial framework that emphasizes the interplay of genetics, neurobiology, psychology, and an individual's social and societal context. There is strong evidence that AUDs are genetically influenced, but with a complex polygenic architecture. Likewise, there is robust evidence for environmental influences, such as adverse childhood exposures and maladaptive developmental trajectories. Well-established biological and psychological determinants of AUDs include neuroadaptive changes following persistent use, differences in brain structure and function, and motivational determinants including overvaluation of alcohol reinforcement, acute effects of environmental triggers and stress, elevations in multiple facets of impulsivity, and lack of alternative reinforcers. Social factors include bidirectional roles of social networks and sociocultural influences, such as public health control strategies and social determinants of health. An array of evidence-based approaches for reducing alcohol harms are available, including screening, pharmacotherapies, psychological interventions and policy strategies, but are substantially underused. Priorities for the field include translating advances in basic biobehavioural research into novel clinical applications and, in turn, promoting widespread implementation of evidence-based clinical approaches in practice and health-care systems.

Moderate alcohol consumption is widespread but its impact on brain structure and function is contentious. The relationship between alcohol intake and structural and functional neuroimaging indices, the threshold intake for associations, and whether population subgroups are at higher risk of alcohol-related brain harm remain unclear. 25,378 UK Biobank participants (mean age 54.9 ± 7.4 years, 12,254 female) underwent multi-modal MRI 9.6 ± 1.1 years after study baseline. Alcohol use was self-reported at baseline (2006-10). T1-weighted, diffusion weighted and resting state images were examined. Lower total grey matter volumes were observed in those drinking as little as 7-14 units (56-112 g) weekly. Higher alcohol consumption was associated with multiple markers of white matter microstructure, including lower fractional anisotropy, higher mean and radial diffusivity in a spatially distributed pattern across the brain. Associations between functional connectivity and alcohol intake were observed in the default mode, central executive, attention, salience and visual resting state networks. Relationships between total grey matter and alcohol were stronger than other modifiable factors, including blood pressure and smoking, and robust to unobserved confounding. Frequent binging, higher blood pressure and BMI steepened the negative association between alcohol and total grey matter volume. In this large observational cohort study, alcohol consumption was associated with multiple structural and functional MRI markers in mid- to late-life.

Alcohol use disorder (AUD) is a chronic, relapsing brain disorder, characterized by compulsive alcohol seeking and disrupted brain function. In individuals with AUD, abstinence from alcohol often precipitates withdrawal symptoms than can be life threatening. Here, we review evidence for nutritional ketosis as a potential means to reduce withdrawal and alcohol craving. We also review the underlying mechanisms of action of ketosis. Several findings suggest that during alcohol intoxication there is a shift from glucose to acetate metabolism that is enhanced in individuals with AUD. During withdrawal, there is a decline in acetate levels that can result in an energy deficit and could contribute to neurotoxicity. A ketogenic diet or ingestion of a ketone ester elevates ketone bodies (acetoacetate, β-hydroxybutyrate and acetone) in plasma and brain, resulting in nutritional ketosis. These effects have been shown to reduce alcohol withdrawal symptoms, alcohol craving, and alcohol consumption in both preclinical and clinical studies. Thus, nutritional ketosis may represent a unique treatment option for AUD: namely, a nutritional intervention that could be used alone or to augment the effects of medications.