Abstract

Kshama P. Mundokar*, Sagar N. Ande and Dr. Pramod V. Burakle

ABSTRACT

Alcohol withdrawal syndrome (AWS) is a complex neurobiological condition that arises from the abrupt cessation or reduction of chronic alcohol consumption. This review comprehensively examines the neurochemical alterations in central neurotransmitter systems that underpin the clinical manifestations of AWS. Chronic alcohol exposure induces neuroadaptive changes in key systems, including γ-aminobutyric acid (GABA), glutamate, dopamine, serotonin, norepinephrine, corticotropin-releasing factor (CRF), the endocannabinoid system, endogenous opioids, and acetylcholine. During withdrawal, a shift toward excitatory dominance is observed, with reduced GABAergic inhibition and elevated glutamatergic transmission contributing to anxiety, seizures, and agitation. Concurrently, dysregulation in dopaminergic and serotonergic pathways results in affective disturbances such as depression, anhedonia, and irritability. Hyperactivity of the noradrenergic and CRF systems further exacerbates autonomic and stress-related symptoms. Additionally, deficits in endocannabinoid and opioid signaling compromise reward processing and stress regulation. This review also outlines pharmacological strategies targeting these systems, including both conventional treatments (e.g., benzodiazepines, acamprosate, naltrexone) and emerging therapies (e.g., cannabidiol, CRF1 antagonists, and plant-based agents). By integrating preclinical and clinical findings, this article highlights the importance of neurotransmitter-specific interventions in both acute withdrawal management and long-term relapse prevention, advocating for a more personalized and multi-targeted approach to treating alcohol use disorder.