Scientists have discovered the impact chronically drinking alcohol can have on the brain.
We already know booze is bad from our health, including waking up with hangxiety and putting our liver through its paces.
Even 'moderate drinking' can rapidly increase the risk of dementia.
But a Spanish post-mortem study examining the brains of people who were dependent on alcohol for an average of 35 years has revealed the true damage it could cause.
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Alcohol use disorder (AUD) is defined by the National Institute on Alcohol Abuse and Alcoholism as 'an impaired ability to stop or control alcohol use despite adverse social, occupational, or health consequences'.
The study, funded by the Spanish Ministry of Health and published in the Addiction journal, looked at the brains of 18 people with AUD.
Samples of brain tissue were provided by the New South Wales Tissue Resource Centre in Australia, from people with chronic AUD who did not take other illegal drugs.
"This approach provides a much clearer picture of how alcohol alone reshapes gene expression in brain regions central to addiction,” professor María Salud García-Gutiérrez, first author of the study, said.
It looked into the endocannabinoid system, which helps regulate mood, pleasure, stress, memory and motivation.
Compared to people without alcohol addiction, those with long-term alcohol use showed major gene changes that make people more vulnerable to addiction.
The CB1 receptor, linked to craving and relapse, was much higher in key decision-making and reward areas, making addictive behavior more likely to be rewarded.
At the same time, CB2, which helps protect the brain and reduce inflammation, was halved, suggesting the brain may be less able to defend itself against alcohol-related damage.
Other changes included GPR55, which increased in the decision-making region but decreased in the reward centre - something never before shown in humans with alcohol addiction.
Meanwhile, the FAAH enzyme shifted in opposite directions in these areas, likely disrupting levels of a 'feel-good' brain chemical.
Together, these shifts suggest alcohol rewires brain signalling in ways that may increase cravings, impair control, and alter mood and stress responses.
Jorge Manzanares, senior author of the study and professor at The Miguel Hernández University, said: "Alcohol use disorder is one of the leading causes of disease and death worldwide, yet despite its enormous social and health impact, available treatment options remain limited.
"Understanding what changes in the brain after decades of alcohol consumption is essential for developing more effective therapies."
The American Medical Association recommends a two-drink daily limit for men, with heavy drinking defined as five or more drinks in one day or 15 or more drinks in a week.
Women should limit drinking to one a day.
Topics: Science, Alcohol, Food and Drink, Health
Ellie Kemp