Editorial reviews clinical, epidemiological and preclinical evidence on alcohol use disorder targets

A 2026 editorial concludes that research on alcohol use disorder has identified several emerging pharmacological targets, while emphasizing that the condition’s biological and environmental complexity complicates therapeutic development. The article summarizes a Research Topic spanning epidemiological modeling, a clinical study of acute alcohol withdrawal and multiple animal experiments involving neurotransmitter systems implicated in alcohol reward, craving and relapse. Most mechanistic findings were obtained in rodent models, and the editorial does not present them as evidence of clinical efficacy in people.

Alcohol use disorder is described in the editorial as a cycle of dysregulation involving brain reward and anti-reward systems. Repeated alcohol use can reduce reward sensitivity and contribute to negative emotional states, compulsive drinking and loss of control despite adverse consequences. The editors also identify it as a public health concern associated with functional impairment and increased risk of chronic diseases, including stroke, cirrhosis and heart disease, as well as accidents, injuries and violence.

One article summarized in the Research Topic assessed trends in the burden of alcohol use disorder among people aged 15–64 from 1990 through 2021 at global, regional and national levels and projected future trends. Cui and colleagues concluded that the disorder remained a substantial contributor to global disease burden in both the historical and projected periods. The authors reported a decline over the preceding 30 years, but also emphasized persistent differences among regions, sexes and age groups. Their analysis therefore supports the need for targeted prevention and treatment strategies, although the projected results are model-based rather than observed future outcomes.

Chen and colleagues conducted a clinical study of 553 patients with excessive alcohol consumption who were hospitalized with acute alcohol withdrawal at a psychiatric hospital in western China between 2014 and 2023. The researchers examined relationships among blood-based indices associated with sarcopenia, pneumonia and delirium. They found that the blood indices were associated with the risk of these complications during acute withdrawal. These observations were drawn from one hospital population and identify an association; the editorial does not establish that such indices are validated clinical tools or that addressing sarcopenia would prevent complications.

Experimental work summarized by the editorial focused on neurotransmitter mechanisms that may contribute to alcohol-related behavior. Cadeddu and colleagues found that GABA-rho receptors in the nucleus accumbens contributed to the alcohol-induced increase in dopamine and in the endogenous glycine-receptor agonists glycine and taurine. The study positions GABA-rho receptors as a potential pharmacological target, but the editorial presents the result as mechanistic research rather than a demonstration of improved treatment outcomes in people with alcohol use disorder.

In a separate animal study, Cantero-García and colleagues administered a single intranasal infusion of neuropeptide galanin (1–15) to male adult Sprague-Dawley rats. The treatment reduced alcohol self-administration and depressive-like behavior in the tested model, with a favorable safety profile reported by the authors. The intervention and outcomes were confined to this preclinical setting; the study did not test a clinical galanin treatment for alcohol use disorder or establish how the result would translate to people.

Broccoli and colleagues combined in vivo pharmacology, genetic targeting and behavioral studies to examine an interaction between dopamine receptor 1 and corticotropin-releasing hormone receptor 1 in intercalating cell masses of the amygdala. The researchers reported that this interaction was involved in maladaptive stress coping, alcohol-related behavior and relapse in their experimental models. The work identifies a circuit-level mechanism that could be relevant to pharmacological intervention, but the editorial does not report a clinical test of a compound acting on that interaction.

Two rodent studies examined fenofibrate, a peroxisome proliferator-activated receptor alpha agonist already used to treat dyslipidemia. In one study, León and colleagues found that fenofibrate treatment during withdrawal reversed symptoms of ethanol-induced depression in male Sprague-Dawley rats. In another, Isla and colleagues reported that fenofibrate restored homeostasis of monoaminergic, glutamate and dopamine systems in the nucleus accumbens and significantly reduced relapse in rats selectively bred for high alcohol consumption. These findings support further investigation of PPAR-alpha activation, but the evidence presented is preclinical.

Taken together, the Research Topic points to a broader set of potential targets than the classical neurotransmitter systems alone, including GABA-rho receptors, galanin signaling, dopamine and corticotropin-releasing hormone receptor interactions, and PPAR-alpha activation. The editorial also highlights persistent regional and demographic disparities in alcohol use disorder burden and complications observed during acute withdrawal. Its overall conclusion is cautious: the collection identifies biologically plausible targets and leads for pharmacological research, but the mixture of modeled burden estimates, an observational clinical study and animal experiments does not demonstrate that interventions at these targets are effective treatments for alcohol use disorder.

Subject of Research: Pharmacological targets and disease burden of alcohol use disorder

Article Title: Editorial: Potential therapeutic targets in alcohol use disorder: insights from recent preclinical studies

Article References: Morella, I., Vázquez-León, P., Vengeliene, V., & Miranda-Páez, A. (2026). Editorial: Potential therapeutic targets in alcohol use disorder: insights from recent preclinical studies. Frontiers in Pharmacology, 17, Article 2015630. https://doi.org/10.3389/fphar.2026.2015630

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.2015630

Keywords: alcohol use disorder, preclinical research, animal models, neurotransmitter systems, acute alcohol withdrawal, GABA-rho receptors, galanin, PPAR-alpha, dopamine, global disease burden, Editorial, Potential