Molecular targets of oleoylethanolamide in the pathogenesis of alcohol use disorder: Mechanisms of central and peripheral action.

Alcohol use disorder (AUD) is a complex disease whose pathogenesis involves profound neurobiological disturbances in reward, stress, and cognitive control systems, as well as systemic peripheral pathological processes, including inflammation and organ damage. Oleoylethanolamide (OEA) - an endogenous lipid mediator synthesized from oleic acid, with the nuclear receptor PPAR-α as its primary target. Accumulated evidence indicates the multi-level therapeutic potential of OEA in correcting key aspects of AUD. Its central action importantly involves the ability to modulate dopaminergic transmission in the reward system and influence the balance of orexin and oxytocin signaling pathways, contributing to a reduction in motivation to consume alcohol. A significant aspect of its activity is its antidepressant and anxiolytic properties, associated with the normalization of monoaminergic neurotransmitter activity and the hypothalamic-pituitary-adrenal (HPA) axis during withdrawal. A substantial contribution to OEA's therapeutic profile is its pronounced anti-inflammatory and neuroprotective action, including strengthening of the intestinal barrier, suppression of neuroinflammatory cascades, and stimulation of neurotrophic support. Furthermore, OEA demonstrates hepatoprotective potential aimed at reducing steatosis, oxidative stress, and inflammation in the liver. Thus, the multi-organ mechanism of action of OEA corresponds to the multifactorial nature of AUD, justifying its consideration as a promising basis for developing comprehensive therapeutic strategies.