Published online Oct 19, 2025. doi: 10.5498/wjp.v15.i10.107936
Revised: May 7, 2025
Accepted: July 23, 2025
Published online: October 19, 2025
Processing time: 178 Days and 19.7 Hours
The glymphatic system, a recently discovered cerebrospinal fluid-mediated pathway, plays a crucial role in fluid exchange and waste clearance in the brain. Its dysfunction has been implicated in various neurological disorders, including Alzheimer’s disease and traumatic brain injury. Recent studies suggest that alcohol intake has a biphasic effect on the glymphatic system: Low doses of alcohol enhance glymphatic function, whereas high doses lead to glymphatic suppression and cognitive decline, mirroring patterns seen in alcohol-related dementia, providing valuable insights into the dose-dependent effects of alcohol on glymphatic function, but significant gaps persist, particularly regarding the mechanistic understanding and the influence of confounding factors such as sex, age, blood pressure, and wakefulness. Here, we synthesize and critically evaluate the important research findings within this field to gauge its progress and identify new research opportunities. We discuss the specific mechanisms by which alcohol affects the glymphatic system, including how alcohol influences cerebrospinal fluid-interstitial fluid exchange and waste removal. We also discuss the potential of the glymphatic system as a new target, such as through pharmacological or lifestyle interventions aimed at enhancing glymphatic function to treat alcohol use disorder and other neurological disorders associated with glymphatic dysfunction.
Core Tip: The glymphatic system, a critical pathway for fluid exchange and waste clearance in the brain, is linked to neurological disorders when dysfunctional. Alcohol has a biphasic effect: Low doses enhance glymphatic function, while high doses suppress it and cause cognitive decline, mirroring alcohol-related dementia. Studies explore how alcohol affects cerebrospinal fluid-interstitial fluid exchange and waste removal. Despite progress, gaps remain in understanding mechanisms and confounding factors like sex, age, and blood pressure. The significance of this review lies in deepening the understanding of the relationship between alcohol and glymphatic system disorders and offering possible targets for developing new treatments.