Use and Efficacy of Ketamine for Alcohol Use Disorder

"The potential use of ketamine for AUD was first suggested in 1972 (32, 33). Possible hypotheses for ketamine use in AUD include balancing cortical glutamate homeostasis and enhancing neuroplasticity which may facilitate learning and acquiring new skills, especially those that help individuals cope with drinking (29, 34). Acute alcohol exposure stimulates the GABA receptors and inhibits the NMDA-glutamate receptors. Chronic alcohol use decreases the concentration of GABA receptors and upregulates NMDA-glutamate receptors. This new balance of inhibitory and excitatory neurotransmitters requires continued regulation with alcohol. Abrupt cessation of alcohol use causes enhanced signaling of the glutamatergic system manifesting as fear, anxiety, and restlessness resulting in a syndrome of alcohol withdrawal. Additionally, the dysregulation of glutaminergic tone results in individuals experiencing alcohol craving. Ketamine mimics some of the mechanisms of action of alcohol through antagonism of the NMDA receptor which may reduce alcohol cravings. Ketamine additionally upregulates the mu and kappa-opioid receptor. The downstream effects are to enhance dopamine secretion which has been described as a mechanism to address depression. For individuals who have AUD, depression is a common comorbidity and may explain some of the potential effects of ketamine on alcohol use (35, 36). Like any substance use, alcohol use can change the neuronal plasticity and lead to formation of maladaptive memories that contribute to increased drug craving and seeking behavior. This neuronal plasticity is partly modulated by the NMDA-glutamate receptor (glutamatergic system) which can be potentially reversed by the inhibitory action on this receptor by ketamine (37, 38). Ketamine can also serve as a potential adjunct in the management of AWS. Ketamine may serve as an adjunct to benzodiazepines in AWS because it acts as an NMDA antagonist and may help to balance cortical glutamate homeostasis faster with decreased sedation time than with benzodiazepines alone (39)."