Alcohol Withdrawal Research Articles

ADVANCEMENTS IN UNDERSTANDING AND MANAGING ALCOHOL WITHDRAWAL SYNDROME: A COMPREHENSIVE REVIEW

Alcohol withdrawal syndrome (AWS) is a clinically significant condition that can arise upon abrupt cessation or reduction of alcohol consumption in individuals with alcohol dependence. This review article provides a comprehensive overview of AWS, encompassing its epidemiology, pathophysiology, clinical manifestations, assessment tools, and management strategies. We discuss the neurobiological mechanisms underlying AWS, including the role of neurotransmitter systems such as gamma-aminobutyric acid (GABA) and glutamate, as well as neuroadaptive changes that occur with chronic alcohol use. Furthermore, we explore the spectrum of clinical manifestations associated with AWS, ranging from mild withdrawal symptoms to severe complications such as delirium tremens and seizures. Diagnostic tools and scoring systems commonly used for assessing AWS severity are examined, along with evidence-based approaches for pharmacological and non-pharmacological management of AWS. Additionally, we highlight emerging research areas and future directions in the field of AWS, including novel treatment modalities and potential biomarkers for predicting withdrawal severity and treatment response. This comprehensive review aims to provide clinicians, researchers, and healthcare professionals with a thorough understanding of AWS to facilitate early recognition, appropriate management, and improved outcomes for individuals affected by this condition.

Evaluation of Noopept Effect on the Neurotransmitter Amino Acids in the Hippocampus in Alcohol Drinking Rats Using in Vivo Microdialysis

The aim of the present work was to study the dynamics of neurotransmitter amino acids after acute Noopept (a dipeptide analogue of piracetam used in clinical practice as a nootropic agent) administration in intact and long-term ethanol (ETOH) exposed rats. Albino male rats were given 10% (vol/vol) ETOH solution as the only source of fluid 24 h / 7 days per week (n = 5). Also we used intact rats of the same age which had no access to ethanol (n = 5). The excitatory and inhibitory amino acids in the extracellular space of the dorsal hippocampus region in freely moving intact and ETOH-exposed rats during prolonged alcohol deprivation were measured using the intracerebral microdialysis method followed by HPLC/ED. There were no significant differences in the level of neurotransmitter amino acids between ETOH-exposed and intact animals. For the first time, in vivo experiments the effect of Noopept (1.5 mg/kg, i.p.) on the level of excitatory amino acids (an increase in ASP by 2.38 times and GLU by 2.28 times) along with an increase in the level of the inhibitory amino acid GLI by 3.13 times only in intact rats was shown. Thus, in ETOH-exposed rats under the adaptive rearrangements in prolonged ethanol withdrawal, the neurochemical mechanisms of the hippocampus seem to be characterized by insensitivity to an acute Noopept administration. Animal neurochemical studies of changes in the mediator amino acids due to the long-term effect of alcohol on the CNS may be of practical importance for the development of optimal strategies and pharmacotherapy.

Severe alcohol withdrawal during pregnancy or early postpartum: maternal and fetal outcomes.

Alcohol withdrawal syndrome (AWS) during pregnancy is under-researched despite growing concerns about increased alcohol use among pregnant women. This study aims to explore the severity of AWS and its impact on maternal and fetal outcomes. This retrospective study reviewed the medical records of patients admitted to the Mayo Clinic who underwent the CIWA-Ar protocol for AWS from June 2019 through June 2022. Pregnant women identified in this cohort had their pregnancy, labor, and neonatal data analyzed for alcohol-related complications and outcomes. Out of the medical records reviewed, 8 cases involved pregnant women experiencing AWS. These cases showed a high severity of withdrawal symptoms, with a median peak CIWA-Ar score of 17 (IQR = 14). Maternal complications included a high rate of ICU admissions (37.5%; n = 3) and significant rates of miscarriage and stillbirth (37.5%; n = 3). Fetal outcomes were concerning, with 1 out of 5 (20%) neonates requiring NICU admission and experiencing conditions such as respiratory failure and neonatal abstinence syndrome. Developmental problems were noted in 2 out of 5 (40%) newborns. The findings highlight the severe implications of AWS during pregnancy, impacting both maternal and fetal health. The severity of AWS requires attentive clinical management and preventative interventions. Future research should focus on larger, prospective studies to better understand and address the risks associated with AWS in pregnant women and to improve health outcomes for mothers and their children. • Severe AWS during pregnancy leads to high ICU admissions and adverse neonatal outcomes. • 37.5% of pregnant women with AWS experienced miscarriage or stillbirth. • 20% of newborns from mothers with AWS required NICU admission for serious conditions; 40% of newborns had developmental problems. • Findings underscore the need for specialized treatment protocols to improve outcomes for pregnant women and their newborns.

Promising strategies for the prevention of alcohol-related brain damage through optimised management of acute alcohol withdrawal: A focussed literature review.

There is an increasing awareness of the link between chronic alcohol consumption and the development of cognitive, behavioural and functional deficits. Currently, preventative strategies are limited and require engagement in dedicated long-term rehabilitation and sobriety services, the availability of which is low. The acute alcohol withdrawal syndrome is an episode of neurochemical imbalance leading to autonomic dysregulation, increased seizure risk and cognitive disorientation. In addition to harm from symptoms of alcohol withdrawal (e.g. seizures), the underpinning neurochemical changes may also lead to cytotoxicity through various cellular mechanisms, which long-term, may translate to some of the cognitive impairments observed in Alcohol-Related Brain Damage (ARBD). Here we review some of the pharmacological and neurochemical mechanisms underpinning alcohol withdrawal. We discuss the cellular and pharmacological basis of various potential neuroprotective strategies that warrant further exploration in clinical populations with a view to preventing the development of ARBD. Such strategies, when integrated into the clinical management of acute alcohol withdrawal, may impact large populations of individuals, who currently face limited dedicated service delivery and healthcare resource.

Plasma neurofilament light chain levels are associated with delirium tremens in patients with alcohol use disorder

Delirium tremens (DT) is the most severe and life-threatening manifestation of alcohol withdrawal. Prompt identification and treatment are crucial in the clinical management of DT, but laboratory markers in this context are still lacking. Neurofilament light chain (NfL) has been proposed as a novel blood marker of neuroaxonal pathology. Therefore, we investigated the association between plasma NfL levels on admission and the occurrence of DT in patients with alcohol use disorder (AUD). NfL levels were measured on admission in 224 patients with AUD undergoing alcohol withdrawal treatment and in 116 healthy individuals. We monitored patients with AUD during the following 2 weeks of hospitalization and categorized them according to the prospective occurrence of DT (n = 25) or not (n = 199). Plasma NfL levels at admission were highest in patients who later developed DT, compared to AUD patients without DT, and healthy individuals (63.1 ± 47.2, 24.0 ± 22.4, 11.8 ± 6.1 pg/mL, respectively, p < 0.001). Receiver operating characteristic analysis revealed that a cut-off NfL level of 27.2 pg/mL could discriminate AUD patients who later developed DT (sensitivity: 80.0 %; specificity: 72.4 %; area under the curve: 0.84, p < 0.001), with an odds ratio of 9.43 (95 % CI 3.26–27.32; p < 0.001) for the risk of developing DT. Our findings suggest that NfL levels at admission may predict DT occurrence in patients with AUD and implicate neuroaxonal pathology in the pathophysiology of DT. Further research is needed to validate these findings and to explore the underlying neurobiological mechanisms.

Review of Attributes and Outcomes of Hospitalized Patients with Alcohol Withdrawal

Review of Attributes and Outcomes of Hospitalized Patients with Alcohol Withdrawal

Evaluating a 30-day alcohol abstinence challenge in heavy-drinking individuals with and without chronic pain: feasibility, safety, and perceived benefits

IntroductionTo combat high-risk alcohol consumption, we introduced a 30-day alcohol abstinence challenge targeted at heavy drinkers with and without chronic pain. Our study aimed to assess the challenge's feasibility and safety and to explore its perceived benefits. Our exploratory aim was to identify participants' coping strategies during the challenge. MethodsOur single-arm study recruited heavy drinkers from a pain clinic and a university setting (n = 34, 64.7% chronic pain). Participants underwent a modified community-based 30-day challenge, which included motivational interviewing, an individualized start date, and weekly phone check-ins. ResultsWe found the 30-day challenge was feasible and safe; 72.3% of eligible heavy drinkers participated in the challenge with no serious adverse events. Most challengers (94.1%) reported some benefit from the challenge, which included improvements in alcohol withdrawal symptoms, sleep, and alcohol abstinence self-efficacy, but not in pain. We identified 25 perceived benefits and 21 coping strategies. ConclusionOur study confirms that a 30-day alcohol abstinence challenge is a feasible and safe intervention for heavy drinkers with and without chronic pain, yielding notable health benefits. The challenge also facilitated the development of effective coping strategies. Future studies should explore the long-term benefits of such interventions in broader outpatient settings.

Association of bone turnover markers and craving reduction in patients with alcohol use disorder during withdrawal: Exploring the role of bone-brain axis.

Alcohol use disorder (AUD) is associated with imbalanced bone turnover and psychological symptoms, but the relationship between bone and brain remains unclear. The study analyzed serum levels of a bone formation marker, procollagen type 1 N-terminal propeptide (P1NP), and bone resorption marker, C-terminal telopeptide of type I collagen (CTX-1), in AUD patients before and after 2 weeks of alcohol withdrawal and investigated their correlation with psychological symptoms. Ninety patients with AUD and 117 healthy controls were recruited. P1NP and CTX-1 levels were measured using Enzyme-Linked Immunosorbent Assay. The Penn Alcohol Craving Scale (PACS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were assessed in the AUD group at baseline, week 1, and week 2 of withdrawal. Baseline CTX-1 levels, along with the CTX-1/P1NP and P1NP/CTX-1 ratio, were higher in the AUD group than controls. Over the 2-week withdrawal, PACS, BDI, and BAI scores demonstrated significant reductions. P1NP (p < 0.001) and P1NP/CTX-1 ratio increased (p < 0.001), while CTX-1/P1NP ratio decreased (p < 0.001), indicating a propensity toward bone formation. Univariate analysis revealed that reductions in PACS, BDI, and BAI scores during withdrawal correlated with increased P1NP levels and decreased CTX-1/P1NP ratios. However, multivariate analysis indicated that only PACS score reductions correlated with these changes. Bone metabolism shifted toward increased bone formation and decreased bone resorption during 2-week alcohol withdrawal. The correlation between improvements in bone turnover markers and reduction in craving scores during withdrawal supports the concept of the bone-brain axis.

Is alcohol use disorder associated with higher rates of depression and anxiety among people with new onset type 2 diabetes? A cohort study using linked primary care data in England

IntroductionDepression and alcohol use disorder (AUD) in people living with Type 2 diabetes mellitus (T2DM) are associated with worse health outcomes. AUD is strongly associated with depression and anxiety, but it is not known how these conditions cluster in people with T2DM. We investigated rates of new episodes of depression and anxiety following T2DM diagnosis in people with and without prior AUD among an English primary care population.MethodsThe study population was people diagnosed with T2DM between 2004 and 2019. We used the Clinical Practice Research Datalink (CPRD) Aurum database and linked Hospital Episode Statistics Admitted Patient Care (HES APC) and Office for National Statistics (ONS) mortality data. We examined incidence of new episodes of anxiety or depression in people with T2DM with and without AUD. AUD was defined as any of i) clinical diagnosis; ii) alcohol withdrawal; or iii) chronic alcohol-related harm (physical or mental) using SNOMED-CT or ICD-10 codes. People were excluded if they had codes for depression/anxiety 12 months prior to T2DM diagnosis. Poisson regression models were fitted adjusting sequentially for a) age, gender, calendar time; b) region, Index of Multiple Deprivation, ethnicity, body mass index, smoking status, Charlson co-morbidity index; and c) history of a mental health condition.ResultsOur study population was 479,447 people of whom 10,983 (2.3%) had an AUD code prior to T2DM diagnosis.After adjusting for all measured confounders except history of a mental health condition, IRR for depression was 2.00 (95% CI 1.93, 2.06) for people with AUD compared to without AUD. This reduced to 1.45 (95% CI 1.41, 1.50) after further adjustment for history of a mental health condition.Findings for anxiety were substantially similar to those for depression (adjusted for all measured confounders except history of a mental health condition, IRR 2.08 95% CI 1.99, 2.18 fully adjusted IRR 1.48 95% CI 1.41, 1.55).ConclusionsPeople with AUD have over double the rates of depression and anxiety following T2DM diagnosis than those without AUD. This was only partially explained by pre-existing diagnoses of mental health conditions. A holistic approach incorporating mental health support is needed to improve health outcomes for people with AUD who develop T2DM.Trial registrationNot applicable.

Ameliorating Effects of Nardostachys Jatamansi And Valeric Acid On Alcohol Withdrawal Induced Anxiety In Wistar Albino Rats.

Ameliorating Effects of Nardostachys Jatamansi And Valeric Acid On Alcohol Withdrawal Induced Anxiety In Wistar Albino Rats.

A Case of Cervical and Thoracic Epidural Abscess Presenting As Diabetic Ketoacidosis Amid Persistent Bacteremia and Alcohol Withdrawal

A Case of Cervical and Thoracic Epidural Abscess Presenting As Diabetic Ketoacidosis Amid Persistent Bacteremia and Alcohol Withdrawal

Relationship of Biochemical and Hematological Markers With Alcohol Withdrawal Severity

Relationship of Biochemical and Hematological Markers With Alcohol Withdrawal Severity

The Role of Propofol in Alcohol Withdrawal Syndrome: A Systematic Review.

The objective of this review was to evaluate the efficacy and safety of propofol in the treatment of critically ill patients diagnosed with alcohol withdrawal syndrome (AWS). A review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria, and Embase, MEDLINE (PubMed), Cochrane CENTRAL, and Web of Science were queried for results through June 2024. Studies providing efficacy or safety data associated with propofol with a reported diagnosis of AWS in critically ill patients were included. Studies evaluating pediatric patients, those without quantitative and qualitative outcome data, and those not readily translatable to English were excluded. Five retrospective cohort analyses of 218 patients were included in this systematic review. Patients were found to have both significant and non-significant increases in time to resolution of AWS symptoms when treated with propofol versus the AWS standard of care. Adjunct treatment with propofol was generally associated with reductions in total benzodiazepine use and increases in both ICU length of stay and duration of mechanical ventilation. The results of this systematic review provide the evidence necessary to support the use of propofol as an efficacious and safe medication in the management of severe and refractory AWS. Further investigation is required to determine optimal dosing strategies and durations of therapy. The results of this systematic review demonstrate the clinical utility of propofol as part of the management strategy for severe and refractory AWS.

How can the benefits of dietetic care be integrated into the treatment of patients undergoing alcohol withdrawal?

How can the benefits of dietetic care be integrated into the treatment of patients undergoing alcohol withdrawal?

Cross-validation of methods for the quantitative determination of phenazepam and its active metabolite in human blood plasma at various extractions

Introduction. In conducting of therapeutic drug monitoring (TDM), often such situation arises where the drug concentration has measured by different methods or in different laboratories. To combine and analyze the data obtained with different methods, it is necessary to perform cross-validation procedure. Insufficient attention is paid to the statistical approaches used for this purpose.Aim. Performing cross-validation of different analytical methods for the quantitative determination of phenazepam (PHEN) and 3-hydroxyphenazepam (3-OH-PHEN) using the Bland – Altman analysis.Materials and methods. PHEN and 3-OH-PHEN concentrations in the blood plasma of patients (n = 100) with alcohol withdrawal syndrome were measured using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). The quantification of both analytes in each sample was measure twice by two different methods: solid phase extraction (SPE) and supported liquid extraction (SLE). Both methods have been fully validated before the experiment began. Cross-validation was performed at the end of the experiment using data from study samples. The Bland – Altman analysis was used to evaluate accuracy and precision. Deming regression was also used to identify a systematic error between measurement results.Results and discussion. The regression equations have been obtained between concentrations both analytes measured by different sample preparation methods. 95 % confidence intervals (CI) of the regression coefficients of both equations included one, and 95 % CI of the intercepts included zero. 95 % CI of the geometric mean of the individual SLE/SPE ratios was within the acceptable range (0.87; 1.15). These results confirm the absence of the influence of quantitative methods on the measurement of both analytes concentration. 66.7 % CI of the percent difference between two measurements was within acceptable limits (–0.2; 0.2), not exceeding 20 % of the range of their mean value. This confirms the acceptable precision between the methods. The estimated CIs were displayed in the Bland – Altman plots.Conclusion. The statistical approaches used in the work have confirmed the reproducibility of the results of different sample preparation methods. In addition to cross-validation, the statistical algorithm from this paper using Bland – Altman analysis can be successfully employed to assess accuracy and precision during bioanalytical method validation and evaluation of the acceptance of analytical runs, as well as to determine the level of reproducibility of incurred samples.

Incidence of Hospitalizations Involving Alcohol Withdrawal Syndrome in a Primary Care Population

Alcohol withdrawal syndrome (AWS) is an important cause and complication of hospitalizations. Although common and preventable, the incidence of AWS during hospitalizations is poorly described. To evaluate the incidence and proportional incidence of hospitalizations involving AWS in an adult primary care population overall and across patient characteristics. This retrospective cohort study used electronic health records and insurance claims from Kaiser Permanente Washington (KPWA) between July 1, 2018, and June 30, 2022. The study included adults with 1 or more primary care visits during this period or the year prior, where primary care included annual standardized alcohol screening using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). Age, sex, race, Hispanic ethnicity, AUDIT-C scores, and comorbid diagnoses. Hospitalizations involving AWS were defined by diagnosis codes documented during hospitalizations (incidence numerator). Time enrolled in KPWA determined person-enrolled-years (incidence denominator). Proportional incidence was calculated as the incidence of hospitalizations involving AWS divided by the incidence of all-cause hospitalizations. Proportional incidence was also estimated for hospitalizations involving other common chronic conditions (chronic obstructive pulmonary disease, diabetes, heart failure, and hypertension), which were also defined using hospital diagnosis codes. Among 544 825 adults engaged in primary care (mean [SD] age, 47.0 [17.9] years; 310 069 [56.9%] female; 3656 [0.7%] American Indian or Alaska Native, 55 206 [10.1%] Asian, 25 406 [4.7%] Black, 5204 [1.0%] Native Hawaiian or Other Pacific Islander, 365 780 [67.1%] White, 19 791 [3.6%] multiracial, 15 963 [2.9%] other races, and 53 819 [9.9%] unknown race; 33 987 [6.2%] Hispanic, 414 269 [76.0%] not Hispanic, and 96 569 [17.7%] unknown ethnicity), incidence of hospitalizations involving AWS was 169 (95% CI, 159-179) per 100 000 person-enrolled-years overall but as high as 15 347 (95% CI, 13 502-17 331) in patients with other alcohol-attributable diagnoses. The proportional incidence of hospitalizations involving AWS was 2.3% overall, with variation by age, sex, and AUDIT-C scores (eg, 9%-11% in male patients aged 30-49 years and 23%-44% in patients with high-risk AUDIT-C scores of 7-12 points). In most cases, among adults younger than 60 years, proportional incidence of hospitalizations involving AWS matched or surpassed that of other common chronic conditions (chronic obstructive pulmonary disease, diabetes, heart failure, and hypertension). In this cohort study of a large primary care population served by an integrated health system, AWS hospitalizations were common, especially in male patients, younger age groups, and individuals with high-risk alcohol use. During hospitalizations, the burden of AWS was similar to or exceeded complications of other chronic diseases that receive greater medical attention.

12475 Revisiting Myxedema Coma

Abstract Disclosure: M.H. Islam: None. D.R. Jimenez Corado: None. S. Siddiqui: None. M.F. Aquino Camey: None. S. Yeasmin: None. Background: Myxedema coma is a rare and life-threatening complication of hypothyroidism.Although it is rare in the era of better diagnostics and treatment modalities, its life-threatening nature mandates its timely recognition and better understanding. Case:81-year-old female with a history of hypothyroidism (unclear medication compliance) and alcohol use disorder was admitted due to alcohol withdrawal and treated with benzodiazepines. A few days prior to the presentation, she was found to have worsening confusion, unsteady gait, and multiple falls. On presentation, she was hemodynamically stable, tremulous, anxious, and oriented to person only. Blood work was remarkable for mild transaminitis. CT scan of the head revealed sequelae of microvascular disease. The day after admission, she was noted to be lethargic, and benzodiazepines were held. Later, she became hypothermic, hypotensive, bradycardic, and hyponatremic. Further investigation was pursued, revealing a TSH of 55 (normal 0.27 to 4.2 mlU/L), free T4 of &amp;lt;0.10 ng/dL (normal 0.8-1.7 ng/dL), free T3 of &amp;lt;1.0 pg/mL (normal 2.2-4 pg/mL), and cortisol of 10.7 ug/dL. Due to concerns of myxedema coma, she was started on stress dose steroids and IV levothyroxine. She was transferred to the ICU as her mental status continued to deteriorate; she underwent endotracheal intubation and received additional doses of IV levothyroxine and liothyronine. After a few days, her clinical condition and her cortisol, free T4, and free T3 levels improved; she was extubated and later discharged with an adjusted levothyroxine dose. Conclusion: It is of absolute importance to keep myxedema coma as a differential diagnosis when evaluating encephalopathic elderly patients, especially those with a history of thyroid disorders.There is a paucity of evidence to suggest a clear benefit of combining levothyroxine-liothyronine over levothyroxine alone. Treating initially with intravenous levothyroxine over oral is beneficial, as GI absorption and bioavailability are likely variable and unpredictable. In this case, oral liothyronine was used with IV levothyroxine to speed up clinical and biochemical recovery.Adrenal insufficiency often coexists with hypothyroidism, with considerable overlap in clinical features like hypotension, hypoglycemia, and hyponatremia. Administration of levothyroxine before steroids can lead to a rapid increase in metabolic rate and subsequent depletion of the existing reserves. Considering this, it can be said with fair confidence that patients need prior or concomitant stress doses of corticosteroids on an emergent basis. Later, biochemical testing can be done to evaluate the functioning of the hypothalamic-pituitary-adrenal axis and then adjust steroid doses accordingly. Presentation: 6/1/2024

Hemodynamic Disorders in Alcohol Withdrawal Syndrome

INTRODUCTION: The introduction of the study is determined by a high prevalence of alcoholism and a high incidence of complications from the cardiovascular system. AIM: To study the features of hemodynamics in patients with uncomplicated alcohol withdrawal syndrome (AWS) and in those with alcohol withdrawal delirium (delirium tremens). MATERIALS AND METHODS: The study enrolled 116 men, 58 of them with uncomplicated AWS, 78 with AWS and delirium. Basic hemodynamic parameters were studied: heart rate (HR), blood pressure (BP), and integral parameters — cardiac index (CI), total peripheral resistance (TPR), shock index (SI). Comparisons between the groups and correlation analysis were conducted to find relationships between hemodynamic parameters and clinical data. RESULTS: In patients with alcoholic delirium, hemodynamic parameters were statistically significantly higher than in patients with uncomplicated AWS: HR (р = 0.003), systolic BP (р = 0.02) and diastolic BP (р = 0.04), while no statistically significant differences in the integral parameters (CI, TPR, SI) were found between the groups. In patients of both groups, CI linearly decreased with age (p 0.0001). The same linearly CI decreased with increase in the duration of alcoholism (p = 0.02). With an increase in the amount of consumed alcohol during the binge period, a linear growth of CI was observed in withdrawal state (p = 0.001). The value of TPR increased with age (p = 0.005). Only in patients with delirium tremens, there was an inverse relationship between SI and partial tension of carbon dioxide in venous blood (r = -0.4; p = 0.014). Besides, only in patients with delirium tremens, by the 7th day of withdrawal, a direct relationship was established between the cardiac index and blood potassium level (r = 0.36; p = 0.03). CONCLUSIONS: There was no significant difference between hemodynamic parameters in uncomplicated AWS and in delirium tremens. CI in patients with uncomplicated AWS and in those with DT decreased with age and with increase in the alcohol load. The vessel tone was inversely proportional to CI throughout the entire period of observation. With the development of delirium, a correlation was noted between a decrease in the level of energy metabolism and the probability for decompensation of systemic circulation. At the stage of reduction of delirium tremens, a correlation was noted between CI and the blood potassium level that reflected the exhaustion of the cardiovascular system and reduction of its compensatory capacities.

Anxiolytic, memory improvement, hepatoprotective, and antioxidant effects of Thymus vulgaris on alcohol withdrawal syndrome in mice

Introduction: Thymus vulgaris is a plant used in Cameroon to alleviate and treat hangover symptoms. This study was conducted to assess the anxiolytic, memory-improving, hepatoprotective, and antioxidant effects of T. vulgaris on alcohol withdrawal syndrome. Methods: In this preclinical study 42 mice were grouped into seven equal sets of normal control, negative control, positive control (piracetam; 200 mg/kg), and test (T. vulgaris; 25, 50, 100, or 200 mg/kg) groups. All mice (except those of the normal control) were administered ethanol by gavage once daily for 28 days. After alcohol withdrawal, behavioral assessments (elevated plus maze, Y-maze, and open field) were performed from day 29 to day 31, one hour following appropriate treatments. Mice were euthanized on day 32 and the brains and the livers were used for histopathological assessment and oxidative stress parameters evaluation. Results: In the elevated plus maze test, T. vulgaris at 100 and 200 mg/kg significantly (P &lt; 0.001) increased the number of entries and the time spent in the open arms. The plant extract (200 mg/kg) significantly (P &lt; 0.001) increased the spontaneous alternation percentage in the Y maze. T. vulgaris administration decreased malondialdehyde (MDA) and nitric oxide (NO) in the brain and liver and increased glutathione (GSH) and catalase (CAT). The plant extract reduced the neuronal degeneration and hepatocyte damage induced by chronic alcohol administration. Conclusion: T. vulgaris had anxiolytic, memory-enhancing, and hepatoprotective properties against alcohol toxicity. These results may justify the use of thyme in traditional pharmacopeia in the management of alcohol use disorders (AUDs).

Serum BDNF and pro-BDNF levels in alcohol use disorders according to depression status: An exploratory study of their evolution two months after withdrawal

BackgroundAlcohol use disorders (AUDs) are complex pathologies with a myriad of molecular actors involved in both disease progression and remission. Brain-derived neurotrophic factor (BDNF) is suspected to be one such actor due to its neurotrophic effects. The BDNF precursor, pro-BDNF, has different effects, as it mainly promotes neuronal apoptosis. Both forms also play a role in depression and depressive episodes (DE). The aim of this exploratory study was to compare serum BDNF and pro-BDNF levels in patients with AUDs after withdrawal and according to DE status with those of controls without AUDs or DE. Materials and methodsNinety-nine AUD patients and 40 controls were included. Questionnaires were used to assess both alcohol and psychiatric domains: the severity of hazardous alcohol consumption was assessed using Alcohol Use Disorders Identification Test (AUDIT), craving was assessed using Obsessive and Compulsive Drinking Scale (OCDS), anxiety was assessed with Hamilton Anxiety Rating Scale (HAM-A) and depression with Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected during two visits: at the time of alcohol withdrawal (M0) and two months later (M2). ELISAs to measure serum BDNF and pro-BDNF levels were performed. AUD patients were categorized according to depression status at M2. Forty-five patients remained abstinent whereas 54 relapsed. BDNF serum levels rose after alcohol withdrawal, but pro-BDNF levels did not vary between M0 and M2. ResultsAUD subjects without DE at M2 had higher BDNF levels at both M0 and M2 than AUD subjects with DE at M2. AUD subjects showed lower MADRS and OCD scores at M2 than at M0. AUD subjects without DE had lower BDNF levels at M0 than controls but not at M2, regardless of abstinence maintenance. ConclusionBDNF serum levels were reduced in AUD patients compared to controls and were further reduced in patients with both AUDs and DE. Alcohol withdrawal treatment was sufficient to induce an increase in serum BDNF levels after 2 months, regardless of whether abstinence was maintained during this time period.