These drugs, called Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs), could represent a hopeful new direction for addressing alcohol and other substance use disorders.

"Early research in both animals and humans suggests that these treatments may help reduce alcohol and other substance use," said lead researcher Lorenzo Leggio, M.D., Ph.D., of the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), both part of the National Institutes of Health (NIH) in Bethesda, Md. "Some small clinical trials have also shown encouraging results."

Current Treatment Options Are Limited

Substance use disorders are identified through four key patterns: physical dependence, risky behavior, social difficulties, and loss of control.

The widespread harm caused by these disorders extends far beyond individual health, affecting families, communities, and societies worldwide. Alcohol, in particular, is considered the most damaging drug overall, contributing not only to health problems but also to traffic accidents and incidents of violence, according to researchers.

Even with the scale of the problem, fewer than one in four people received treatment for alcohol or other substance use disorders in 2023.

The authors point to numerous barriers, including stigma and limited resources for patients and providers. "Current treatments for [alcohol and other substance use disorders] fall short of addressing public health needs," the study noted.

GLP-1 Drugs and Their Potential Role in Addiction

GLP-1 medications have recently gained fame for their success in reducing appetite and promoting weight loss.

Beyond their effects on digestion, GLP-1 molecules play a major role in the brain. Activation of GLP-1 receptors in the central nervous system helps regulate hunger signals, prompting people to eat when hungry and stop when satisfied.

The study highlights that some forms of obesity share biological and neurological traits with addiction, though this idea remains debated.

"Pathways implicated in addiction also contribute to pathological overeating and obesity," the study says.

Recognizing this overlap, scientists began exploring GLP-1 drugs as a possible treatment for substance use disorders. Early studies in animals and humans suggest that these drugs may influence the brain circuits that drive addictive behavior, potentially lowering cravings and use while also benefiting other coexisting health issues.

Evidence from Early Research

Studies that examine GLP-1 effects on substance use disorders include:

• Alcohol use disorder (AUD): A randomized controlled trial with exenatide, the first GLP-1receptor agonist approved for diabetes, showed no significant effect on alcohol consumption, although a secondary analysis indicated reduced alcohol intake in the subgroup of people with AUD and comorbid obesity. A more recent randomized controlled trial showed that low-dose semaglutide -- a newer GLP-1 receptor agonist approved for both diabetes and obesity -- reduced laboratory alcohol self-administration, as well as drinks per drinking days and craving, in people with AUD.
• Opioid use disorder: In rodent models, several GLP-1 receptor agonists have been shown to reduce self-administration of heroin, fentanyl and oxycodone. The studies also found that these medications reduce reinstatement of drug seeking, a rodent model of relapse in drug addiction.
• Tobacco use disorder: Preclinical data show that GLP-1 receptor agonists reduce nicotine self-administration, reinstatement of nicotine seeking, and other nicotine-related outcomes in rodents. Initial clinical trials suggest the potential for these medications to reduce cigarettes per day and prevent weight gain that often follows smoking cessation.

The Road Ahead

Leggio and his colleagues emphasize that more research is needed to confirm how effectively GLP-1 drugs treat addiction and to understand the underlying biological mechanisms.

Despite the unanswered questions, researchers remain optimistic.

"This research is very important because alcohol and drug addiction are major causes of illness and death, yet there are still only a few effective treatment options," Leggio said. "Finding new and better treatments is critically important to help people live healthier lives."

Other study authors are Nirupam M. Srinivasan of the University of Galway in Galway, Ireland; Mehdi Farokhnia of NIDA and NIAAA; Lisa A. Farinelli of NIDA; and Anna Ferrulli of the University of Milan and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) MultiMedica in Milan, Italy.

Research reported in this article was supported in part by NIDA and NIAAA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Investigating the Mystery of the 1812 Retreat

Napoleon's invasion of Russia in 1812, known as the "Patriotic War of 1812," ended in one of history's most disastrous retreats. To better understand what role disease may have played in this collapse, researchers from the Institut Pasteur's Microbial Paleogenomics Unit partnered with the Laboratory of Biocultural Anthropology at Aix Marseille University. The team analyzed the DNA of 13 French soldiers exhumed in 2002 from a burial site in Vilnius, Lithuania, uncovered during archaeological excavations led by the Aix-Marseille University group. Using next-generation sequencing technology on ancient DNA, they searched for genetic traces of infectious organisms.

The researchers detected two distinct disease agents: Salmonella enterica subsp. enterica (serovar Paratyphi C), which causes paratyphoid fever, and Borrelia recurrentis, the bacterium responsible for relapsing fever. The latter is transmitted by lice and produces alternating periods of fever and recovery. Although different, both infections can cause severe fever, exhaustion, and digestive distress. Their combined impact could have intensified the soldiers' suffering at a time when cold, hunger, and poor sanitation were already taking a heavy toll.

Genetic Evidence From Napoleonic Soldiers

Out of the 13 soldiers examined, DNA from S. enterica Paratyphi C was found in four individuals, and B. recurrentis was detected in two. This marks the first direct genetic confirmation that these pathogens were present in Napoleon's army. Their exact contribution to the enormous death toll remains uncertain, but the findings complement earlier research that identified Rickettsia prowazekii (the cause of typhus) and Bartonella quintana (responsible for trench fever), both long suspected of spreading through the ranks during the retreat.

Because only a small number of samples could be analyzed compared to the thousands of remains in Vilnius, researchers cannot yet determine how widespread these infections were. The tested soldiers represent a tiny fraction -- 13 out of more than 3,000 bodies at the site and roughly 500,000 to 600,000 troops who took part in the campaign, of whom about 300,000 died during the retreat.

Understanding the Past to Protect the Future

"Accessing the genomic data of the pathogens that circulated in historical populations helps us to understand how infectious diseases evolved, spread and disappeared over time, and to identify the social or environmental contexts that played a part in these developments. This information provides us with valuable insights to better understand and tackle infectious diseases today," explains Nicolás Rascovan, Head of the Microbial Paleogenomics Unit at the Institut Pasteur and last author of the study.

To achieve these results, the team worked in collaboration with scientists from the University of Tartu in Estonia to develop an innovative authentication workflow involving several steps, including a phylogeny-driven interpretive approach for the highly degraded genome fragments recovered. This method enables scientists to accurately identify pathogens even if their DNA only yields low coverage, in some cases even indicating a specific lineage.

"In most ancient human remains, pathogen DNA is extremely fragmented and only present in very low quantities, which makes it very difficult to obtain whole genomes. So we need methods capable of unambiguously identifying infectious agents from these weak signals, and sometimes even pinpointing lineages, to explore the pathogenic diversity of the past," he adds.

Linking History and Disease

The team's results closely match the historical descriptions of the fevers that swept through Napoleon's forces. This connection strengthens the theory that infectious diseases contributed to the disastrous outcome of the 1812 campaign, along with other factors such as exhaustion, starvation, and the brutal Russian winter.

Napoleon's 1812 campaign ultimately ended in defeat, forcing a massive withdrawal that devastated his army. The Russian forces reclaimed Moscow, marking a turning point that dealt a fatal blow to Napoleon's military ambitions.