Therapeutic potential of ketamine for alcohol use disorder

Introduction

Excessive alcohol consumption imposes a large public-health and economic burden and current pharmacotherapies for Alcohol Use Disorder (AUD) are modestly effective. AUD is neurobiologically complex, involving dysregulation across dopaminergic, cholinergic, noradrenergic, serotonergic, opioid, GABAergic and glutamatergic systems, together with alterations in synaptic plasticity, hippocampal neurogenesis and neural connectivity. Comorbid conditions such as major depression and post-traumatic stress disorder (PTSD) commonly coexist with AUD, and negative affect and stress are important drivers of relapse. Given that ketamine has demonstrated rapid antidepressant and anxiolytic effects and modulates glutamatergic signalling, synaptic plasticity and neurogenesis, it has been proposed as a candidate pharmacotherapy to target mechanisms implicated in AUD and relapse. Worrell and colleagues set out to synthesise preclinical and clinical evidence on ketamine as a potential treatment for AUD. The review examines neurobiological rationale, mechanisms of action, results from completed and ongoing human trials of ketamine for AUD and other substance use disorders (SUDs), relevant preclinical findings including sex-specific effects, candidate biomarkers of response and risks related to ketamine’s abuse liability. The authors frame the paper as a narrative review drawing clinical-trial registry searches and PubMed queries to identify relevant studies and trials.