Unlabelled: Preclinical and clinical work suggests that mifepristone (glucocorticoid receptor antagonist), may be a viable treatment for alcohol use disorder (AUD). The aim of this work was to translate our preclinical mifepristone study using yohimbine (α2 receptor antagonist) stress-induced reinstatement of alcohol-seeking to a clinical setting. This was a Phase 1/2, outpatient, cross-over, randomized, double-blind, placebo-controlled trial with non-treatment-seeking individuals with AUD ( =32). We investigated the safety, alcohol craving and consumption after oral administration of mifepristone (600mg daily for a week) in a human laboratory study comprised of administration of yohimbine in a cue-reactivity procedure and alcohol self-administration. Outcomes were assessed using Generalized Estimating Equations and mediation and moderation analyses assessed mechanisms of action and precision medicine targets. We did not observe serious adverse events related to the study drugs or study procedure and mild to moderate non-serious adverse events were reported by both study conditions. Also, there was no statistically-significant difference between the mifepristone and placebo in the hemodynamic response, alcohol subjective effects and pharmacokinetics parameters. Mifepristone significantly reduced alcohol craving and increased cortisol levels. Mifepristone-induced cortisol increase was not a mediator of alcohol craving. Moderation analysis with family history density of AUD (FHDA) and mifepristone, suggested that reduced craving was present in individuals with , but not FHDA. Mifepristone, compared to placebo, did not reduce alcohol consumption in the laboratory or in a naturalistic setting. This study successfully translated a preclinical paradigm to a human laboratory study confirming safety, tolerability and efficacy of mifepristone in an alcohol paradigm. Mediation analysis showed that the effect of mifepristone on craving was not related to mifepristone-induced increases in cortisol and moderation of FHDA suggested the importance of evaluating AUD endophenotypes for pharmacotherapies.
Clinical Trial Registration: Clinicaltrials.gov ; NCT02243709.
Ind/fda: 121984, mifepristone and yohimbine (Holder: Haass-Koffler).
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http://dx.doi.org/10.1101/2023.01.02.23284122 | DOI Listing |
Ther Adv Drug Saf
January 2025
Pharmacology Department, School of Medicine, University of Valladolid, Valladolid, Spain.
In 2019, intranasal esketamine gained approval as a promising therapy for those individuals grappling with treatment-resistant depression. Both clinical trials and real-world studies have underscored its efficacy in alleviating and remitting depressive symptoms, with sustained benefits observed for nearly 4.5 years.
View Article and Find Full Text PDFSubst Use Misuse
January 2025
Psychological Sciences Department, Western Kentucky University, Bowling Green, KY, USA.
Background: Alcohol use among emerging adults is a public health concern, as it has been associated with numerous negative consequences. Poor sleep has repeatedly been associated with alcohol-related consequences in this age group, yet factors impacting this relationship and potential moderators remain largely unexplored.
Objectives: The primary objective of this study was to examine the indirect effect of poor sleep quality on alcohol-related consequences through alcohol craving and to determine whether depression moderates this association.
Drug Alcohol Depend Rep
March 2025
Radboud University, Postbus 9102, Nijmegen 6500 HC, the Netherlands.
Introduction: Ecological momentary assessment (EMA) is popular in smoking research to study time-varying processes and design just-in-time personalised cessation interventions. Yet, research examining the psychometric properties of EMA and user experiences with EMA protocols is lacking. We conducted a mixed-methods study to test the EMA component of a mobile intervention for middle to late-aged adolescents (16-20 years) who smoke cigarettes at least weekly.
View Article and Find Full Text PDFSleep Med Rev
January 2025
Faculty of Medicine, Department of Psychiatry, University of Geneva, Geneva, Switzerland.
Insomnia is prevalent among patients with alcohol use disorder (AUD), potentially undermining treatment and increasing the risk of relapse. Cognitive behavioral therapy for insomnia (CBT-I) is the recommended first-line treatment for insomnia, but its efficacy is not well-characterized in patients across the spectrum of AUD. The aim of this meta-analysis was to quantify the effectiveness of CBT-I in improving insomnia severity and alcohol-related outcomes in adults with heavy alcohol use and/or varying levels of AUD severity and comorbid insomnia.
View Article and Find Full Text PDFDigit Health
January 2025
Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Background: Advancing evidence-based, tailored interventions for substance use disorders (SUDs) requires understanding temporal directionality while upholding ecological validity. Previous studies identified loneliness and craving as pivotal factors associated with alcohol consumption, yet the precise directionality of these relationships remains ambiguous.
Objective: This study aims to establish a smartphone-based real-life intervention platform that integrates momentary assessment and intervention into everyday life.
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