Researchers at Washington University School of Medicine in St. Louis found that GLP-1 medications were associated with lower risks of developing substance use disorders involving alcohol, nicotine, cannabis, cocaine, opioids, and other substances. The drugs were also linked to fewer overdoses, hospitalizations, and drug-related deaths among people already living with addiction.

The findings were published in The BMJ.

GLP-1 Drugs and Addiction

GLP-1 receptor agonists were originally developed to help manage type 2 diabetes, but their popularity has surged in recent years because of their effectiveness for weight loss. Along the way, researchers began noticing something unexpected.

Some patients reported losing interest in alcohol and cigarettes after starting the medications. Earlier observational studies also found links between GLP-1 treatment and lower risks of alcohol and cannabis use disorders, opioid overdose, and alcohol-related hospitalization.

However, most previous studies focused on individual substances. Researchers wanted to determine whether the effects extended across multiple forms of addiction and whether the drugs could help reduce the most serious consequences associated with substance use disorders.

To investigate, the research team analyzed electronic health records from 606,434 U.S. veterans with type 2 diabetes.

Study Examines More Than 600,000 Veterans

Participants were divided into two groups. One group included people without a substance use disorder at the start of the study. The second group consisted of people who already had a diagnosed substance use disorder.

Researchers reviewed up to three years of health records after participants began taking either a GLP-1 receptor agonist, most commonly semaglutide, liraglutide, or dulaglutide, or an SGLT2 inhibitor, another type of diabetes medication.

Among the 524,817 participants who did not have a substance use disorder when the study began, those taking GLP-1 medications were less likely to develop one over time.

Compared with patients taking non-GLP-1 diabetes medications, GLP-1 users had a 14% lower risk of developing any substance use disorder. Risks were lower across every major substance examined, including alcohol (18%), cannabis (14%), cocaine (20%), nicotine (20%), and opioids (25%).

The researchers estimated that this translated to seven fewer new substance use disorder diagnoses per 1,000 GLP-1 users.

Fewer Overdoses and Drug-Related Deaths

The study also examined outcomes among the 81,617 participants who already had a substance use disorder.

In that group, GLP-1 use was associated with fewer addiction-related emergencies and serious health consequences. After three years, participants taking GLP-1 drugs experienced a 30% reduction in emergency department visits, a 25% reduction in hospitalizations, a 40% reduction in overdoses, and a 50% reduction in drug-related deaths.

Overall, the researchers estimated that GLP-1 use was associated with 12 fewer serious addiction-related events per 1,000 users.

“In addiction medicine, a lot of treatments target just one thing, for example, a nicotine patch helps with smoking, but not alcohol, but there is no medication that works across addictive substances, let alone all of them,” said senior author Ziyad Al-Aly, MD, a WashU Medicine clinical epidemiologist and Chief of the Research and Development Service at the VA Saint Louis Health Care System.

“The revelation about GLP-1 medication is that it really works against all major substances, and it works uniformly, not because it acts against alcohol or opioids or nicotine specifically, but because it is likely acting against the craving itself. It blunts that craving that pulls people toward whatever they’re addicted to.”

Targeting the Biology of Craving

Al-Aly said the study was partly inspired by patient reports describing unexpected changes in behavior after starting GLP-1 treatment.

Researchers also considered evidence showing that GLP-1 receptors are present in brain regions involved in reward processing. That raised the possibility that the drugs could influence the cravings that drive addiction.

The findings suggest that GLP-1 medications may act on a shared biological pathway underlying multiple forms of addiction. Rather than targeting a specific substance, the drugs may be affecting the craving itself.

The idea is particularly significant because some addictive substances, including methamphetamine, currently have no approved medication treatments.

“GLP-1s may offer a dual benefit for patients with chronic conditions like diabetes or obesity who are also struggling with a substance use disorder: one medication can treat both conditions at once,” Al-Aly said.

A Potential New Approach to Addiction Treatment

Millions of Americans already use GLP-1 medications, and that number continues to grow. If future studies confirm these findings, the public health implications could be substantial.

The researchers say the results support conducting clinical trials specifically designed to test GLP-1 drugs as addiction treatments, including studies capable of measuring effects on overdose and drug-related death.

“People taking these drugs for obesity often describe a quieting of ‘food noise,’ the persistent preoccupation with food that drives overeating,” Al-Aly said.

“What our study suggests is something broader: GLP-1 drugs may also quiet what I call ‘drug noise,’ the relentless craving that drives addiction across substances. That cross-substance signal points to a shared biology underlying addiction, and it opens the door to a fundamentally different approach: not treating one addiction at a time, but targeting that common biologic signal, that common craving across addictions. Moving beyond food noise to drug noise, GLP-1s are quieting the roar of addiction.”

The research was funded by the U.S. Department of Veterans Affairs. According to the authors, the funders had no role in the study’s design, data collection, analysis, interpretation, manuscript preparation, review, approval, or publication decisions. The researchers also noted that the findings do not represent the views of the Department of Veterans Affairs or the U.S. government.

“Certain bacteria seem to offer protection, which is exciting because it suggests there could be ways to support a child’s development through diet or probiotics in the future,” says senior author and gastroenterologist Francis Ka Leung Chan of The Chinese University of Hong Kong.

How Early Biology Shapes Development

The first few years of life are a critical period for both brain development and the maturation of the immune system. Previous research has shown that epigenetics and the gut microbiome can each influence long-term health, but scientists have had limited understanding of how these two systems interact during early life.

“We wanted to see how the epigenome and microbiome interact in early life and if their interaction could influence a child’s risk of developing neurodevelopmental conditions like ASD and ADHD,” says co-senior author and public health researcher Hein Min Tun of The Chinese University of Hong Kong. “We discovered a kind of conversation happening: a baby’s epigenetic setting at birth can influence their risk for neurodevelopmental disorders, but the presence of certain ‘good’ bacteria in their gut can step in and modify the risk.”

To investigate, the research team analyzed DNA methylation patterns, a common form of epigenetic modification, in umbilical cord blood from 571 infants. They combined those data with gut microbiome samples collected from 969 infants at 2, 6, and 12 months of age, along with microbiome samples from the infants’ parents during the third trimester of pregnancy.

When the children reached 36 months of age, researchers assessed their neurodevelopment using a behavioral questionnaire and looked for connections between developmental outcomes, gut microbes, and epigenetic patterns.

Factors That Influence the Infant Microbiome

The researchers found that several factors were associated with epigenetic patterns at birth, including delivery method, length of pregnancy, having older siblings, and maternal allergies. Interestingly, parental gut microbiomes did not appear to influence these birth-related epigenetic changes.

The development of the infant microbiome was linked to a different set of factors. Delivery method, antibiotic exposure, older siblings, and breastfeeding all played a role in shaping the community of microbes that developed during the first year of life.

Babies delivered by Caesarean section showed distinct DNA methylation patterns in several genes involved in immune function and brain development.

A Link Between Gene Regulation and Gut Bacteria

The study also revealed that epigenetic patterns present at birth affected how the gut microbiome evolved during infancy.

Infants who had higher levels of DNA methylation in certain immune-related genes tended to develop less diverse gut microbiomes by 12 months of age. These genes are involved in helping the body recognize and respond to pathogens.

The results suggest that biological signals present at birth may help guide the development of the gut microbial community during a child’s first year.

Gut Microbes and Neurodevelopmental Risk

When researchers examined behavioral outcomes at age three, they found that signs of ASD and ADHD were associated with specific combinations of epigenetic markers and gut microbes.

However, the findings also pointed to a potentially protective role for certain bacteria. Children who carried epigenetic patterns associated with ASD were less likely to show signs of the condition if they acquired Lachnospira pectinoschiza during infancy. Similarly, children with epigenetic patterns associated with ADHD appeared less likely to show signs of the disorder if they acquired Parabacteroides distasonis during their first year.

“The foundations for brain health are laid very early, even before birth,” says Tun. “However, we don’t want people to think this means a child’s developmental path is fixed at birth. These are complex conditions with many causes, and we’ve only uncovered a small piece of a very large puzzle.”

Future Possibilities for Probiotics and Brain Health

The researchers are continuing to follow the participating children to better understand how early-life epigenetic patterns and microbiome development influence health later in childhood. They emphasize that laboratory studies will be needed to confirm the observed relationships between gut bacteria and neurodevelopment.

“The ultimate goal is to develop safe, non-intrusive early interventions such as specific probiotics or live biotherapeutics, that could help nurture a healthy gut microbiome and potentially reduce the risk of neurodevelopmental challenges,” says first author and gastroenterologist Siew Chien Ng of The Chinese University of Hong Kong.

The study was supported by InnoHK, the Government of Hong Kong, the D. H. Chen Foundation, and the New Cornerstone Science Foundation.

Scientists call this process soil respiration, and it represents one of the largest carbon flows on Earth.

New research suggests that this natural rhythm is being disrupted by a growing and often overlooked form of pollution: excess nitrogen.

Nitrogen Pollution Is Reaching Forests Worldwide

On a cool spring morning, a forest floor may seem calm and still. Yet beneath the surface, billions of microbes are hard at work decomposing leaves, wood, and other organic matter. At the same time, tiny roots release carbon dioxide as they grow and function.

Together, these processes create a steady exchange of carbon between the land and the atmosphere.

For decades, however, forests have been exposed to increasing amounts of nitrogen pollution. Fertilizers, vehicle emissions, and industrial activities release reactive nitrogen into the air, much of which eventually returns to the ground through rain, snow, or airborne particles.

Since the Industrial Revolution, human activities have roughly tripled global nitrogen deposition.

Scientists have long known that excess nitrogen affects forest ecosystems. What remained unclear was why some studies found that nitrogen increased soil respiration while others found the opposite effect.

Solving a Longstanding Forest Mystery

To investigate, an international team of researchers assembled one of the largest datasets ever used to study soil respiration.

The analysis combined:

• 168 nitrogen addition experiments conducted in forests around the world
• 3,689 observations of natural soil respiration
• Global maps showing nitrogen limited and nitrogen saturated forests
• High resolution nitrogen deposition data
• Measurements of both root respiration and microbial respiration

The team then used machine learning to model how forests worldwide respond to increasing nitrogen inputs.

Their conclusion was surprisingly simple: forests do not all react the same way. Instead, they generally follow one of two distinct pathways.

When Nitrogen Acts Like a Fertilizer

In forests where nitrogen is scarce, additional nitrogen can initially stimulate biological activity.

These nitrogen limited forests are often found in boreal regions and remote mountain landscapes.

When nitrogen becomes available, microbes become more active, roots grow faster, and organic matter breaks down more quickly. As a result, soil respiration increases.

But the benefits do not continue indefinitely.

As nitrogen levels keep rising, the positive effects begin to fade. Toxicity can develop, readily available carbon sources become depleted, and the increase in soil respiration eventually levels off before declining.

Researchers describe this pattern as an inverted U shaped response. Soil respiration rises, reaches a peak, and then begins to fall.

When Nitrogen Pushes Forests Past Their Limits

The picture looks very different in forests that already contain high levels of nitrogen.

In these nitrogen saturated ecosystems, additional nitrogen can push the system beyond its tolerance threshold.

Microbial communities change. Sensitive species disappear. Fine roots shrink or die back. Soil acidity increases.

Rather than showing a gradual response, soil respiration can drop sharply.

According to the study, this type of abrupt decline is common in regions that have experienced heavy nitrogen pollution for decades, including parts of Europe, eastern China, and the eastern United States.

As a result, two forests receiving similar amounts of nitrogen may respond in completely different ways. One may experience increased soil activity, while another may suffer a major decline.

A Hidden Climate Connection

The findings matter because soil respiration is enormous on a global scale.

Researchers estimate that carbon released through soil respiration is seven to eight times greater than annual fossil fuel emissions produced by humans.

Even relatively small changes can have significant implications.

Overall, the study found that nitrogen deposition increases global soil respiration by roughly 5%. Most forests remain nitrogen limited enough that additional nitrogen still stimulates biological activity.

However, the decline in respiration observed in nitrogen saturated forests is not necessarily good news.

Lower carbon dioxide emissions from soil in these areas often reflect declining root activity and shrinking microbial populations. These are key components of healthy ecosystems and play important roles in building and maintaining soil carbon stores.

In other words, less carbon dioxide release may sometimes signal a loss of ecosystem resilience rather than an environmental benefit.

A New Framework for Predicting Forest Responses

By combining thousands of observations with decades of ecological research, the scientists developed a new framework that helps explain both the gradual and abrupt responses observed around the world.

The framework incorporates:

• Biochemical limits
• Species specific nitrogen tolerance
• Changes in community composition
• Ecological tipping points
• Global nitrogen deposition patterns

For the first time, researchers say they can more reliably predict how nitrogen pollution will influence soil respiration across the planet.

Why Reducing Nitrogen Pollution Matters

Efforts to reduce nitrogen pollution are already underway because of concerns about biodiversity loss and air quality.

The new findings suggest another important benefit.

Reducing nitrogen inputs from agriculture, transportation, and industry could help protect the carbon stored in forest soils.

By preventing ecosystems from crossing nitrogen saturation thresholds, forests may be better able to maintain their natural carbon cycling processes and remain resilient as the climate continues to change.

Collaborators: Land-CRAFT at Aarhus University, Stanford University, National Forestry and Grassland Administration Harbin China, Pacific Northwest National Laboratory, Chinese Academy of Sciences, Beijing Normal University, Maastricht University, SLAC National Accelerator Laboratory, Duke University, and Karlsruhe Institute of Technology.

Funding: This work was financially supported by the National Natural Science Foundation of China (32430067, 32588202, 42141004) and the National Key R&D Program of China (2023YFF1305900, 2022YFF080210102) received by N.H., and the Pioneer Center for Landscape Research in Sustainable Agricultural Futures (Land-CRAFT), DNRF grant number P2 received by K.B.B.

That water comes from a single source: Roaring Springs, a cave-fed spring on the North Rim. Although hikers can hear and glimpse the spring from the North Kaibab Trail, there is no trail leading directly to it. Roaring Springs provides water not only for park visitors but also for the plants, animals, and ecosystems that depend on it. As the region becomes hotter and drier, protecting this vital water source is becoming increasingly important.

Researchers at Northern Arizona University’s School of Informatics, Computing, and Cyber Systems are working to better understand how Roaring Springs and other cave-fed springs function. With support from a new grant funded by Grand Canyon National Park, the team will expand efforts to map these water systems and investigate how snowmelt is connected to the springs.

“Understanding where the water sinks is critical for the infrastructure, the animals, the plants and the rest of the ecosystems that rely on these springs,” said Blase LaSala, a Ph.D. student in ecoinformatics. “They’re like oases.”

Early findings from the project were recently published in Scientific Reports.

Mapping the Grand Canyon’s Hidden Caves

Most people will never enter the caves that feed Grand Canyon springs. They are closed to the public and often located far from established trails. As a result, much of what scientists know about them comes from specialized mapping projects.

For his doctoral research, LaSala worked with professor Temuulen “Teki” Sankey, an expert in remote sensing, to create detailed maps of several cave systems. Using a mobile lidar scanner, the team produced high-resolution three-dimensional models that captured cave walls, ceilings, passages, and chambers in remarkable detail.

Over 45 days, researchers, volunteers, and park staff documented more than 10 kilometers of underground passages and rooms.

“I had no idea how large and long these caves are,” Sankey said. “We have been able to produce really high-resolution 3D maps, which, from a remote sensing perspective, is what’s unique and novel about it. Grand Canyon’s caves have never been mapped in 3D like this.”

The work required major logistical effort. Team members carried packs weighing up to 55 pounds, including lidar equipment, while hiking to remote cave entrances that could take as long as two days to reach. Once inside, they climbed, rappelled, crawled, and even floated through flooded sections while recording the caves’ shapes and fracture patterns.

Those details are valuable because cave formation follows recognizable geological processes. The arrangement of passages, cracks, and openings can reveal how water travels through different layers of rock beneath the canyon.

Following Snowmelt to Roaring Springs

The simplest explanation for where the water comes from is the surface, particularly snowmelt from the Kaibab Plateau.

The more difficult question is how that water travels underground before emerging at springs like Roaring Springs.

The cave-fed springs are located within Redwall and Muav limestone formations. Several other rock layers sit between those springs and the surface above. Previous dye tracing experiments conducted by the park have shown that water can move surprisingly quickly through this underground system.

Abe Springer, a professor in NAU’s School of Earth and Sustainability and a collaborator on the project, has worked with the park on dye tracing studies. In some tests, dye poured into sinkholes on the plateau traveled roughly 20 kilometers and appeared at springs in as little as a week.

Exactly how the water moves through the subsurface remains uncertain. Factors such as fractures, faults, rock permeability, and underground pathways all influence the journey.

“The dissertation work was making the geologic connection between what we might see at the surface versus what we might see hundreds or thousands of feet belowground,” Sankey said.

“It’s like looking at a black box,” LaSala added. “You see what comes in and what comes out, but it’s very hard to quantify what’s going on in there. Now that we know what patterns are there, we can really start to relate the data to spring change over time.”

Water Quality and Contamination Risks

Understanding these underground pathways is important for more than scientific curiosity. It also has practical implications for water quality and public safety.

The Grand Canyon’s largest springs are fed by karst systems, which Sankey compares to “Swiss cheese” because of the numerous holes, channels, and openings in the rock. Water can move rapidly through these pathways, leaving little opportunity for natural filtration.

That means contaminants may travel quickly as well. Runoff from wildfire burn areas or bacteria such as E. coli could enter sinkholes connected to Roaring Springs Cave and reach the water supply. If contamination is detected, park officials may need to temporarily shut down pumping operations until the issue is addressed.

By identifying where water enters the system and tracing how it moves, researchers can help managers pinpoint contamination sources and reduce the risk of future disruptions.

New Research on Snowmelt and Sinkholes

The next phase of the project is scheduled to begin in early 2026.

Using airborne lidar surveys and satellite observations collected over several decades, LaSala and Sankey plan to map sinkholes on both sides of the Grand Canyon while examining patterns of snow accumulation and snowmelt over the last 40 years.

Much of the upcoming work will focus on surface features, although researchers remain interested in exploring newly discovered caves if opportunities arise.

The goal is to better understand the geological processes that influence sinkhole formation, disappearing streams, and underground water movement. Researchers will compare patterns observed at the surface with those documented inside caves. The findings will also guide future dye tracing experiments.

Snowmelt is an especially important focus because Arizona has experienced declining snow levels over time, and the Grand Canyon region has followed the same trend.

The project will create an extensive archive of environmental data that can be combined with lidar and other imaging resources to improve understanding of water systems throughout the region.

Why the Findings Matter Beyond Arizona

Although the research directly benefits Grand Canyon National Park, its significance extends well beyond northern Arizona.

More than one billion people around the world rely on water from karst springs. Improving scientists’ understanding of how water moves through these complex underground systems could help inform water management efforts globally.

The findings may also prove valuable for Native American tribes located within or near the park.

“It’s exciting to find patterns that verify the hypotheses made over 50 years ago,” LaSala said. “We have all this amazing data now, and we’re trying to combine it with other data to find useful things. There are so many places that could benefit from this type of analysis.”

How the Dragon Bravo Fire Affects the Study

Researchers expect the Dragon Bravo Fire to influence future observations, but they view it as another factor to incorporate into their work rather than an obstacle that changes the overall mission.

When asked how the fire might affect the project, both LaSala and Sankey acknowledged that unexpected developments are common in scientific research.

“It’s a new twist to our study,” Sankey said.

The fire’s effects on the Kaibab Plateau will likely alter some of the environmental conditions researchers are monitoring. As the project continues, those changes will be incorporated into the analysis, and the team plans to assist the park however possible in understanding the fire’s impacts.