Novel Targets Explored in the Treatment of Alcohol Withdrawal Syndrome

Abstract

Alcohol Withdrawal Syndrome (AWS) is characterized as the termination of chronic and sustained alcohol use that leads to severe symptoms of distress or loss of daily functions when less or no alcohol is consumed. It is a debilitating manifestation of alcohol dependence and responds poorly to the available clinical therapies. Alcohol drinking is continuously increasing all over the world. It causes 3.3 million deaths every year (5.9% of all deaths) and 5.1% of the global burden of disease. Alcohol Withdrawal syndrome leads to various changes in the brain's neurotransmitters system, such as GABA, glutamate, non-epinephrine, serotonin. These symptoms arose from the imbalance in brain receptors between gamma-aminobutyric acid (GABA) and N methyl aspartate (NMDA) that develop on the discontinuation of alcohol. Studies from various in vivo and in vitro animal models of alcohol withdrawal explored new targets for the treatment of alcohol withdrawal syndrome. Advancements in the elucidation of the AWS mechanism have revealed a number of key targets that hypothesize to modulate clinical status. The present review discusses the pathophysiology, neurobiology, and treatment of alcohol withdrawal syndrome and its novel targets like corticotrophin-releasing factor, sigma, melanocortin-4 receptors, opioid, potassium channels, ghrelin, and endocannabinoid receptors, and gut microbiota. This review discusses the various clinical and pre-clinical aspects related to alcohol dependence. The exploration of novel pharmacological targets may provide effective therapeutic interventions for the management of alcohol withdrawal syndrome.