Long-Term Effects of Alcohol on the Brain

Published February 23, 2026 – 12:44 p.m. | Reading time: 2 min

Alcohol’s detrimental effects extend beyond the liver and heart, deeply impacting the brain’s biological control mechanisms. New research illuminates the genetic-level changes that occur in the brains of individuals with chronic alcohol use, offering insights into addiction and potential treatment avenues.

The Endocannabinoid System and Alcohol Addiction

Alcohol addiction is a leading cause of illness and death globally, yet effective treatment options remain limited. A research team from the Spanish National Research Council and Miguel Hernández University in Elche, Spain, investigated the impact of decades of alcohol consumption on the human brain at a genetic level. Their study, published in the journal “Addiction”, focused on the endocannabinoid system – a crucial signaling network regulating mood, stress responses, memory, motivation, and reward.

This system includes receptors like CB1 and CB2, the body’s own messenger substances, and enzymes such as FAAH and MGLL, which break down these substances.

Analyzing Brain Tissue of Chronic Alcohol Users

Researchers analyzed brain tissue from deceased individuals who had chronically consumed alcohol for an average of 35 years, ensuring none had used other drugs. This allowed for a focused investigation into the specific effects of alcohol. “This approach provides a much clearer picture of how alcohol alone alters gene expression in brain regions central to addiction,” stated study author María Salud García-Gutiérrez.

Key Brain Regions Affected

The study examined two central areas of the mesocorticolimbic system: the prefrontal cortex and the nucleus accumbens. The prefrontal cortex controls judgment, planning, and impulse control, while the nucleus accumbens plays a vital role in reward processing and habit formation.

Gene Expression Changes

Analysis revealed significant changes in gene expression – the activity of genes and their production of proteins.

• CB1 Receptor: Activity increased by 125% in the prefrontal cortex and 78% in the nucleus accumbens. Increased CB1 activity is closely linked to reinforcing addictive behaviors and the risk of relapse.
• CB2 Receptor: Gene activity decreased by approximately 50% in both brain regions. Reduced CB2 activity suggests a weakening of the brain’s defense mechanisms against alcohol-related damage, as CB2 has anti-inflammatory functions.
• GPR55 Receptor: Gene activity increased by 19% in the prefrontal cortex but decreased by 51% in the nucleus accumbens.
• FAAH Enzyme: Activity decreased in the prefrontal cortex but increased by 24% in the nucleus accumbens.

Implications for Addiction Treatment

These findings provide a deeper understanding of the neurological changes associated with long-term alcohol use and may pave the way for more targeted addiction treatments. Further research is needed to identify the specific molecules involved and develop therapies that interrupt the cycle of negative reinforcement, potentially weakening the brain’s link between alcohol cues and stress relief.

Recent studies also highlight the long-term effects of alcohol abuse on specific brain regions and circuits involved in decision-making. Research from Johns Hopkins University demonstrates that chronic alcohol exposure can lead to impairments in value computations in the striatum, contributing to poor decision-making even after prolonged withdrawal. A study by Scripps Research identified a brain circuit involving the paraventricular nucleus of the thalamus (PVT) that drives addiction by linking alcohol to relief from withdrawal pain.