Therapeutic potential of ketamine for alcohol use disorder.

Excessive alcohol consumption contributes to one in ten deaths of U.S. working-age adults and costs the country about $250 million yearly. Alcohol Use Disorder (AUD) involves changes in synaptic plasticity, hippocampal neurogenesis, and neural connectivity. Depressed mood and stress are major relapse determinants, and AUD frequently co-occurs with depression and stress disorders. Current medications (disulfiram, naltrexone, acamprosate) have limitations. Ketamine, an NMDA receptor antagonist used in anesthesia, affects neurotransmitter systems, synaptic plasticity, neurogenesis, and neural connectivity. It has strong support for treating depression and stress disorders like PTSD, and preliminary evidence for treating substance use disorders. This review explores behavioral and neural evidence for ketamine therapy in AUD.

Study at a glance

Abstract

Excessive alcohol consumption is involved in 1/10 of deaths of U.S. working-age adults and costs the country around $250,000,000 yearly. While Alcohol Use Disorder (AUD) pathology is complex and involves multiple neurotransmitter systems, changes in synaptic plasticity, hippocampal neurogenesis, and neural connectivity have been implicated in the behavioral characteristics of AUD. Depressed mood and stress are major determinants of relapse in AUD, and there is significant comorbidity between AUD, depression, and stress disorders, suggesting potential for overlap in their treatments. Disulfiram, naltrexone, and acamprosate are current pharmacotherapies for AUD, but these treatments have limitations, highlighting the need for novel therapeutics. Ketamine is a N-methyl-D-Aspartate receptor antagonist, historically used in anesthesia, but also affects other neurotransmitters systems, synaptic plasticity, neurogenesis, and neural connectivity. Currently under investigation for treating AUDs and other Substance Use Disorders (SUDs), ketamine has strong support for efficacy in treating clinical depression, recently receiving FDA approval. Ketamine's effect in treating depression and stress disorders, such as PTSD, and preliminary evidence for treating SUDs further suggests a role for treating AUDs. This review explores the behavioral and neural evidence for treating AUDs with ketamine and clinical data on ketamine therapy for AUDs and SUDs.