Chronic alcohol consumption profoundly alters the expression of genes in the endocannabinoid system in key brain regions

“Alcoholism is one of the leading causes of disease and death worldwide, yet despite its social and health impact, available therapeutic options remain limited”

…the study focused on analysing the neurobiological mechanisms associated with alcohol use disorder by examining post-mortem brain tissue from individuals who had consumed alcohol chronically for an average of 35 years. Specifically, the researchers investigated changes in the endocannabinoid system, which is closely linked to reward and addiction mechanisms.

The endocannabinoid system is a chemical communication network that regulates essential functions such as pleasure, memory, mood, and stress response. It is composed of receptors such as CB1 and CB2, their natural ligands, and enzymes responsible for their degradation, including FAAH and MGLL. “This system acts as a fine modulator of brain function and plays a central role in reward and motivation processes”, explains Manzanares.

The researchers analysed two core areas of the mesocorticolimbic system: the prefrontal cortex, which is associated with judgement, planning, and decision-making, and the nucleus accumbens, considered the central hub of reward and habit formation.

By comparing samples from individuals with alcohol use disorder with those from non-addicted individuals, the team observed a marked imbalance in the expression of several endocannabinoid system genes. In particular, they detected a strong increase in the CB1 receptor: expression of the gene encoding this receptor rose by 125% in the prefrontal cortex and by 78% in the nucleus accumbens. “This receptor is closely involved in the reinforcement of addictive behaviours and the risk of relapse”, notes researcher María Salud García Gutiérrez, first author of the study.

In contrast, expression of the CB2 receptor gene was reduced by approximately 50% in both regions. “Since the CB2 receptor plays neuroprotective and anti-inflammatory roles, its reduction suggests an impairment of the brain’s defence mechanisms against alcohol-induced damage”, explains the researcher.

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