Alcohol ranks among the world’s most harmful drugs. Despite being deeply embedded in our culture and rarely perceived as a drug, its long-term consequences are severe. Alcohol dependence is one of the leading causes of death globally, with approximately 3.3 million people dying annually from alcohol-related causes.
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A new study has now shown that chronic alcohol use leads to drastic changes in the endocannabinoid system. The endocannabinoid system is one of the body’s most complex regulatory mechanisms. Dysfunctions in this delicate and intricate system can trigger a range of serious health consequences.
Examining the Brains of Deceased Patients
A recently published Australian study examined brain tissue from deceased patients to understand how long-term alcohol consumption affects the endocannabinoid system. For this purpose, 18 deceased individuals were selected who had been alcohol-dependent for an average of 35 years. To isolate the effects of alcohol specifically, only individuals who consumed no other drugs alongside alcohol were studied.
This was compared against 18 individuals who had not consumed alcohol. The average age in both groups was approximately 55 years. Researchers extracted tissue samples from the brain and examined how alcohol altered the expression of various cannabinoid receptors across different brain regions. The differences discovered were striking.
Drastic Changes in Cannabinoid Receptors
Compared to the control group, alcohol-dependent individuals showed significantly higher levels of CB1 receptors. The prefrontal cortex of alcohol-dependent patients had 125% more CB1 receptors than the control group. In the nucleus accumbens, CB1 receptor levels were increased by 78%. Currently, it remains unclear to what extent these changes are reversible. Earlier studies have shown that CB1 receptor density does not decrease even after one month of abstinence.
Researchers suspect that the increased production of CB1 receptors is associated with addictive behavior and the tendency to relapse after withdrawal. Conversely, alcohol consumption dramatically reduced CB2 receptors. Alcoholics showed 50% fewer CB2 receptors in the prefrontal cortex. In the nucleus accumbens, their numbers had decreased by 49%. The CB2 receptor plays a central role in regulating numerous inflammatory processes. Researchers believe that CB2 receptor reduction contributes to the development of cognitive deficits in long-term alcohol consumption.
Neurodegenerative processes that contribute to cognitive decline occur partly through inflammatory mechanisms—a process largely controlled by the CB2 receptor. Significant changes were also observed in the GPR55 receptor. Alcohol-dependent individuals had 19% more receptors in the prefrontal cortex, while their numbers in the nucleus accumbens were reduced by 51%.
Changes in Enzymes
The enzymes of the endocannabinoid system also appear to be altered by long-term alcohol consumption. Effects on the enzyme FAAH (fatty acid amide hydrolase) were detected. In the prefrontal cortex, this enzyme’s concentration decreased by 15%, while in the nucleus accumbens it increased by 24%. FAAH plays a central role in regulating many processes within the endocannabinoid system.
Among other functions, FAAH is responsible for breaking down the endogenous cannabinoid anandamide. A decline was also observed in the enzyme MAGL. This enzyme is responsible for breaking down the endocannabinoid 2-AG. Researchers believe that the resulting elevated 2-AG levels in the blood also contribute to addictive behavior in alcohol-dependent individuals. It can increase stress-induced alcohol cravings. Simultaneously, an imbalance between 2-AG and MAGL promotes neurodegenerative processes, which are also a typical late consequence of alcohol dependence.
Research Findings Could Contribute to New Treatment Methods
Researchers hope these results will provide better understanding of how alcohol-related diseases develop. Future treatment methods could be derived from these research findings. Although alcohol abuse is a widespread health problem, therapeutic options remain relatively limited today. Excessive alcohol consumption damages virtually every organ, including the brain.
Based on these insights, researchers hope to develop new treatment methods to better counteract the neurodegenerative damage caused by alcohol. Further research is needed, but current findings suggest a connection between the endocannabinoid system, alcohol’s toxic consequences, and the development of addiction.









































