Effects of a novel GABA-B positive allosteric modulator, ASP8062, on alcohol cue-elicited craving and naturalistic alcohol consumption in a multisite randomized, double-blind, placebo-controlled trial.

Background: The γ-aminobutyric acid-B (GABA) receptor is a promising target for the development of new medications to treat alcohol use disorder (AUD). The GABA agonist baclofen has been reported to reduce alcohol consumption but is associated with some undesirable side effects, including sedation. ASP8062 is a novel compound that acts as a positive allosteric modulator at the GABA receptor and may be more tolerable than baclofen.

Complete genome sequences of sp. strain MM2321 and sp. strain MM2322, isolated from a sand sample in Harsewinkel, Germany.

We cultivated bacteria contained in a sandy soil sample, isolated DNA from a single bacterial colony, and assembled from genomic reads the full genome sequence of and strains, termed MM2321 and MM2322. Besides the genome sequences, the phylogenetic classifications of both strains are reported.

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD.

Fossilized anuran soft tissues reveal a new taphonomic model for the Eocene Geiseltal Konservat-Lagerstätte, Germany.

The Eocene Geiseltal Konservat-Lagerstätte (Germany) is famous for reports of three dimensionally preserved soft tissues with sub-cellular detail. The proposed mode of preservation, direct replication in silica, is not known in other fossils and has not been verified using modern approaches. Here, we investigated the taphonomy of the Geiseltal anurans using diverse microbeam imaging and chemical analytical techniques.

Defining Recovery From Alcohol Use Disorder: Development of an NIAAA Research Definition.

The objective of this article is to provide an operational definition of recovery from alcohol use disorder (AUD) to facilitate the consistency of research on recovery and stimulate further research. The construct of recovery has been difficult to operationalize in the alcohol treatment and recovery literature. Several formal definitions of recovery have been developed but have limitations because 1) they require abstinence from both alcohol and substance use, 2) they do not include the DSM-5 diagnostic criteria for AUD as part of the recovery process (i.

Effects of Alcohol Cue Reactivity on Subsequent Treatment Outcomes Among Treatment-Seeking Individuals with Alcohol Use Disorder: A Multisite Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline.

Background: The alcohol cue reactivity paradigm is increasingly used to screen medications for the treatment of alcohol use disorder (AUD) and other substance use disorders. Yet, its prospective association with craving and naturalistic drinking outcomes in clinical trials remains unknown. This study embedded repeated human laboratory assessments of alcohol cue reactivity within the context of a randomized controlled trial to examine the effects of varenicline tartrate (Chantix ), a partial agonist of α4β2 nicotinic acetylcholine receptors, on alcohol craving among treatment-seeking heavy drinkers with AUD.

World Health Organization risk drinking level reductions are associated with improved functioning and are sustained among patients with mild, moderate and severe alcohol dependence in clinical trials in the United States and United Kingdom.

Aims: To examine whether World Health Organization (WHO) risk-level reductions in drinking were achievable, associated with improved functioning and maintained over time among patients at varying initial alcohol dependence severity levels. Design and setting Secondary data analysis of multi-site randomized clinical trials: the US Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study and the UK Alcohol Treatment Trial (UKATT).

Participants: Individuals with alcohol dependence enrolled in COMBINE (n = 1383; 68.

Medication Development for Alcohol Use Disorder: A Focus on Clinical Studies.

Compared to other medical disorders, including other brain diseases, the number of medications approved for alcohol use disorder (AUD) is very small. Disulfiram, naltrexone (oral and long-acting), and acamprosate are approved by the US Food and Drug Administration (FDA) to treat patients with AUD. These medications are also approved in other countries, including in Europe, where the European Medicines Agency (EMA) also approved nalmefene for AUD.

Reduction in non-abstinent World Health Organization (WHO) drinking risk levels and drug use disorders: 3-year follow-up results in the US general population.

Background: To provide information on the clinical relevance of a reduction in the World Health Organization (WHO) drinking risk categories, we examined their relationship to an important indicator of how individuals feel and function: drug use disorders (DUDs), i.e., those involving substances other than alcohol.

Maintenance of World Health Organization Risk Drinking Level Reductions and Posttreatment Functioning Following a Large Alcohol Use Disorder Clinical Trial.

Background: Reductions in the World Health Organization (WHO) risk drinking levels have been proposed as an alternative primary outcome for alcohol clinical trials. Yet, little is known about whether reductions in WHO risk drinking levels can be maintained over time. The current study examined whether reductions in WHO risk drinking levels were maintained for up to 1 year following treatment, and whether reductions over time were associated with improvements in functioning.

Evaluation of Drinking Risk Levels as Outcomes in Alcohol Pharmacotherapy Trials: A Secondary Analysis of 3 Randomized Clinical Trials.

Importance: The US Food and Drug Administration recognizes total abstinence and no heavy drinking days as outcomes for pivotal pharmacotherapy trials for alcohol use disorder (AUD). Many patients have difficulty achieving these outcomes, which can discourage seeking treatment and has slowed the development of medications that affect alcohol use.

Objective: To compare 2 drinking-reduction outcomes with total abstinence and no heavy drinking outcomes.

Reduction in non-abstinent WHO drinking risk levels and depression/anxiety disorders: 3-year follow-up results in the US general population.

Background: Non-abstinent drinking reductions that predict improvement in how individuals feel or function, such as the World Health Organization (WHO) drinking risk levels, may be useful outcomes in clinical trials for alcohol use disorders (AUD).

Methods: Current drinkers in a U.S.

Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety.

Background: Several single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT ), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD).

Methods: Men and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.

Drinking Risk Level Reductions Associated with Improvements in Physical Health and Quality of Life Among Individuals with Alcohol Use Disorder.

Background: Abstinence and no heavy drinking days are currently the only Food and Drug Administration-approved end points in clinical trials for alcohol use disorder (AUD). Many individuals who fail to meet these criteria may substantially reduce their drinking during treatment, and most individuals with AUD prefer drinking reduction goals. One- and two-level reductions in World Health Organization (WHO) drinking risk levels have been proposed as alternative end points that reflect reduced drinking and are associated with reductions in drinking consequences, improvements in mental health, and reduced risk of developing alcohol dependence.

Reduction in Nonabstinent WHO Drinking Risk Levels and Change in Risk for Liver Disease and Positive AUDIT-C Scores: Prospective 3-Year Follow-Up Results in the U.S. General Population.

Background: Abstinence is often the treatment aim for alcohol use disorders (AUD), but this may deter individuals who prefer drinking reduction goals from entering treatment, and be an overly restrictive end point in alcohol clinical trials. Nonabstinent drinking reductions that predict improvement in how individuals feel or function may be useful clinical trial outcomes, for example, reductions in the 4-category World Health Organization (WHO) drinking risk levels. To investigate the clinical relevance of these reductions, we examined their relationship with 2 outcomes of interest to medical providers: liver disease, and positive scores on an alcohol screening measure.

Patterning Highly Conducting Conjugated Polymer Electrodes for Soft and Flexible Microelectrochemical Devices.

There is a need for soft actuators in various biomedical applications to manipulate delicate objects such as cells and tissues. Soft actuators are able to adapt to any shape and limit the stress applied to delicate objects. Conjugated polymer (CP) actuators, especially in the so-called trilayer configuration, are interesting candidates for driving such micromanipulators.

Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities.

Importance: Fetal alcohol spectrum disorders are costly, life-long disabilities. Older data suggested the prevalence of the disorder in the United States was 10 per 1000 children; however, there are few current estimates based on larger, diverse US population samples.

Objective: To estimate the prevalence of fetal alcohol spectrum disorders, including fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder, in 4 regions of the United States.

Advances in Pharmacotherapy Development: Human Clinical Studies.

For more than 25 years, researchers have made advances in developing medications to treat alcohol use disorder (AUD), highlighted by the US Food and Drug Administration's (FDA's) approval of disulfiram, naltrexone (oral and long-acting), and acamprosate. These medications are also approved in Europe, where the European Medicines Agency (EMA) recently added a fourth medication, nalmefene, for AUD. Despite these advances, today's medications have a small effect size, showing efficacy for only a limited number of individuals with AUD.

Change in non-abstinent WHO drinking risk levels and alcohol dependence: a 3 year follow-up study in the US general population.

Background: Alcohol dependence is often untreated. Although abstinence is often the aim of treatment, many drinkers prefer drinking reduction goals. Therefore, if supported by evidence of benefit, drinking reduction goals could broaden the appeal of treatment.

Temporal Stability of Heavy Drinking Days and Drinking Reductions Among Heavy Drinkers in the COMBINE Study.

Background: Recently, the Food and Drug Administration (FDA) proposed to expand the options for primary end points in the development of medications for alcohol use disorder to include either abstinence from alcohol or a nonabstinent outcome: no heavy drinking days (with a heavy drinking day defined as more than 3 drinks per day for women and more than 4 drinks per day for men [>3/>4 cutoff]). The FDA also suggested that 6 months would be the most appropriate length for a clinical trial to demonstrate the stability of this nonabstinent drinking outcome. However, few alcohol clinical trials have examined the stability of nonheavy drinking during and after treatment.

Differences Between Treatment-Seeking and Nontreatment-Seeking Alcohol-Dependent Research Participants: An Exploratory Analysis.

Background: Alcoholism is a chronic relapsing disorder with complex behavioral and functional heterogeneity. To date, attempts to characterize subgroups of alcohol-dependent (AD) individuals have largely been focused on categorical distinctions based on behaviors such as ability to abstain, age of onset, and drinking motives, but these have failed to yield predictors of treatment response and disease course. The distinction between AD individuals who are or are not interested in treatment holds significant implications for interpreting results of human laboratory studies with nontreatment seekers and clinical trials with treatment-seeking AD patients.

Posttreatment Low-Risk Drinking as a Predictor of Future Drinking and Problem Outcomes Among Individuals with Alcohol Use Disorders: A 9-Year Follow-Up.

Background: Treatment for alcohol use disorders (AUDs) has traditionally been abstinence oriented, but new research and regulatory guidelines suggest that low-risk drinking may also be an acceptable treatment outcome. However, little is known about long-term outcomes for patients who become low-risk drinkers posttreatment. This study explores a posttreatment low-risk drinking outcome as a predictor of future drinking and psychosocial outcomes over 9 years.