Therapeutic Interventions Targeted at Problematic Use of Digital Technology: Systematic Review and Meta-Analysis of Evidence

Background: Problematic use of digital technology has increased across the world. Despite growing research, evidence on treatment effectiveness across digital behaviors remains fragmented. Objective: This study aimed to systematically evaluate and compare the effectiveness of therapeutic interventions targeted at problematic use of digital technology across various behavioral domains. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines (PROSPERO: CRD420251052442). Electronic searches of PubMed, Scopus, and Embase (up to April 2025) were conducted. It identified 125 eligible studies, including 73 randomized controlled trials (RCTs), 32 non-RCTs, 14 pre-post studies, and 6 pilot studies. The interventions that were assessed in these studies included psychological therapies, digital or web-based programs, exercise-based interventions, pharmacological treatments, neuromodulation, parent-focused programs, virtual reality–based interventions, educational programs, and multicomponent approaches. Random-effects meta-analyses using standardized mean differences (SMDs) were performed. Results: For problematic internet use, psychological treatments showed a strong effect (effect size=−2.68; <.001). Digital interventions also showed significant benefit (effect size=−1.16; <.001). For smartphone addiction, psychological treatments (effect size=−1.49; <.001) and exercise-based programs (effect size=−3.07; =.001) showed significant improvement. For gaming disorder, psychological treatments showed improvement (effect size=−1.01; =.02), but results were mixed. There were limited studies to calculate pooled results for social media addiction, pornography use, gambling, screen time, and over-the-top content watching. No treatment studies were found for problematic over-the-top content watching. High heterogeneity and evidence of small-study effects were observed in several studies. Conclusions: Overall, structured psychological therapies showed the most consistent benefit. These findings support structured interventions that aim for control of use and reduce cues linked to high use. Evidence remains limited for several emerging digital behaviors. More high-quality studies are needed in clinical settings and for less-studied forms of digital addiction.

Supreme Court extends mifepristone deadline

Get your daily dose of health and medicine every weekday with STAT’s free newsletter Morning Rounds. Sign up here.

Good morning. My co-workers and pals Isabella Cueto and Lev Facher have been talking about alcohol for years. As STAT’s reporters on chronic disease and addiction, respectively, it’s right at the intersection of their beats, yet rarely covered as a public health issue. I’m happy to share that all their talking turned to reporting, and now an incredible series. The first parts are up now. Scroll down or skip ahead to start reading

Read the rest…

The Download: a Nobel winner on AI, and the case for fixing everything

This is today’s edition of The Download, our weekday newsletter that provides a daily dose of what’s going on in the world of technology.

Three things in AI to watch, according to a Nobel-winning economist

A few months before he won the Nobel Prize in economics in 2024, Daron Acemoglu published a paper that earned him few fans in Silicon Valley. He argued that AI would give only a small boost to US productivity and would not eliminate the need for human work.

Two years later, Acemoglu’s measured take has not caught on. The technology has advanced quite a bit since his cautious predictions, but the data is still largely on his side. 

MIT Technology Review spoke with him to understand if any of the latest developments have changed his thesis. Here are the three things Acemoglu is paying closest attention to in AI right now.

—James O’Donnell

This story is from The Algorithm, our weekly newsletter giving you the inside track on all things AI. Sign up to receive it in your inbox every Monday. 

The case for fixing everything

Stewart Brand, the counterculture icon and tech industry legend, considers maintenance a “civilizational” act. His new book argues that taking responsibility for maintaining something, whether a motorcycle, a monument, or the planet, can be radical.

Brand argues that maintainers haven’t gotten the laurels they deserve—and he’s right. Yet his vision of maintenance often feels solitary: profound, but more about personal fulfillment than tending to a shared world or making it better.

Read the full review of his handsome new book, Maintenance: Of Everything, Part One.

—Lee Vinsel

Lee Vinsel is an associate professor of science, technology, and society at Virginia Tech, a cofounder of The Maintainers, and the host of Peoples & Things, a podcast about human life with technology.

This story is from the latest edition of our print magazine, which is all about nature. Subscribe now to read the full issue and receive future print copies once they land.

The must-reads

I’ve combed the internet to find you today’s most fun/important/scary/fascinating stories about technology.

1 The first zero-day exploit built by AI has been discovered
Google spotted and stopped the attempted “mass exploitation event.” (CNBC)
+ The hackers used AI to discover an unknown bug. (NYT $)
+ AI-powered hacking has exploded into an industrial-scale threat. (Guardian)
+ New tools are simplifying online crime. (MIT Technology Review)

2 OpenAI just launched its answer to Claude Mythos
Daybreak patches vulnerabilities before attackers find them. (The Verge)
+ Sam Altman said it will “continuously secure software.” (Gizmodo)
+ It will rival Anthropic’s Claude Mythos, which arrived a month ago. (BBC)
+ OpenAI is allowing wider access to its cyber models than Anthropic. (CNBC)

3 Trump is heading to China to spread the gospel of American tech
While taking cues from Beijing’s more stringent approach. (Guardian)
+ But investors want Trump and Xi to stay out of AI’s way. (Reuters $)
+ Elon Musk and Tim Cook are joining him on the trip this week. (BBC)

4 Ilya Sutskever has testified on Sam Altman’s “pattern of lying”
OpenAI co-founder Sutskever took the stand in the Altman v. Musk trial. (BI)
+ He said he spent a year gathering proof of Altman’s dishonesty. (Reuters $)
+ But he also added to OpenAI’s defense. (Wired $)
+ While Satya Nadella called attempts to remove Altman “amateur city.” (FT $)
+ Here’s what happened last week in the trial. (MIT Technology Review)

5 A new hantavirus vaccine is in the works
Moderna and Korea University are developing an mRNA vaccine. (Wired $)
+ Here’s what you need to know about the cruise ship outbreak. (MIT Technology Review)

6 Texas has sued Netflix over alleged data harvesting and “addictive” design
AG Ken Paxton accuses Netflix of secretly collecting and selling user data. (Quartz)
+ And spying on children while deliberately fostering addiction. (Guardian)

7 A data center guzzled 30 million gallons of water—and no one noticed
The curious case serves as a warning for other data center projects. (Ars Technica)

8 Europe is reportedly selling spyware to human rights abusers
EU states allegedly sold the tech to countries violating rights. (Bloomberg $)

9 The US government’s AI vetting announcement has mysteriously vanished
It had detailed a security test agreement with Google, xAI, and Microsoft. (Gizmodo)

10 Amazon staff are using AI for pointless tasks just to inflate usage scores
In a bid to impress managers. (FT $)
+ An AI expert says we should stop using AI so much. (MIT Technology Review)


Quote of the day

“This is like the cheating husband complaining about the cheating wife.” 

—Anupam Chander, a professor of law and technology at Georgetown Law School, tells the New York Times that Elon Musk’s hypocrisy over OpenAI becoming a for-profit company will undermine his courtroom battle with Sam Altman.

One More Thing

""

STUART BRADFORD


How sounds can turn us on to the wonders of the universe

For decades, astronomy has relied on visual information to make sense of the cosmos: images, charts, and graphs. Now, some researchers are trying something different: listening to the universe.

Using sonification, the process of turning information into sound, they’re helping blind and visually impaired researchers explore the cosmos—and even uncover patterns that might otherwise go unnoticed. The approach is spreading beyond astronomy into fields like climate science, navigation, and education.

Discover how sound could make science more accessible—and even more revealing.

—Corey S. Powell

We can still have nice things

A place for comfort, fun, and distraction to brighten up your day. (Got any ideas? Drop me a line.)

+ This musical mashup beautifully blends LCD Soundsystem with Twin Peaks.
+ Match your speculative ideas to sci-fi stories with the Extrapolated Futures Archive.
+ A live-action animation Coyote vs. ACME is coming soon—and the first trailer just dropped.
+ Want to surf elsewhere in the galaxy? Here’s what it would be like to catch waves on distant planets.

Opinion: STAT+: Pharma and biotech leaders are destroying their own industry

In early 2025, biotech experienced a “DeepSeek moment” when biotech and pharma leaders alike realized how quickly China was gaining ground with innovation, speed of drug development, and share of licensing deals. In 2020, global pharmaceutical companies spent about $9 billion on licensed drug assets from China. In 2025, that number shot to more than $137 billion. The first two months of 2026 alone accounted for nearly $50 billion in deals. As a December 2025 report from the National Security Commission on Emerging Biotechnology put it, “in just three years, China’s biopharmaceutical industry rose from near irrelevance to dominance.”

China’s rise is happening with the blessing of U.S. pharmaceutical executives, who are allowing their own industry to be destroyed.

I am a co-chair of a working group at the Council on Foreign Relations investigating the U.S.’s generic pharmaceutical dependence on China. An estimated 60% of our generic medications have an active ingredient that originates in China; some estimates have this figure as high as 80-90%. (The exact percentage is unknown because the Food and Drug Administration doesn’t formally track this information, and because a significant percentage of our drugs are imported from India, which in turn imports chemical precursors from China.)

Continue to STAT+ to read the full story…

Integrating dual-process decision making and social dynamics: A formal modeling framework for addiction.

Psychological Review, Vol 133(4), Jul 2026, 864-891; doi:10.1037/rev0000584

Currently, formal models of addiction focus either on the complex individual decision-making processes involved in addiction or on the social dynamics of addiction. They do not integrate these two levels, which has been identified as a key shortcoming of current formal models of addiction. To address this, we propose a nonlinear dynamical modeling framework of addiction integrating both the individual level and social level of addictive behavior. The individual level of our modeling framework is a formalization of a dual-process theory, where one type of process increases the consumption of addictive goods, and another type of process limits consumption. For our formalization, we build on a well-studied model from ecology, originally used to model periodic outbreaks of the spruce budworm population. To this model, we add the process of incentive sensitization at the individual level and at the social level, we incorporate the critical processes of selection homophily and peer influence. We show that our integrated modeling framework can be used to explain key phenomena identified in addiction literature: a gradual transition to heavy use, sudden relapse and sudden quitting, relatively stable use states over time (i.e., abstinence moderate use, and heavy use), social contagion and sudden outbreaks, clustering of users, and social aid in recovery. In addition, we demonstrate how our modeling framework can be extended to include mutualistic, competitive, and more complex interactions between different addictive behaviors. Finally, we show how our framework can lead to new insights and predictions and suggest avenues for future research. (PsycInfo Database Record (c) 2026 APA, all rights reserved)

STAT+: Trump pivots on kratom derivative 7-OH, floating approval for some forms

President Trump on Monday suggested the federal government could move to approve some forms of 7-OH, an opioid derived from the naturally occurring kratom plant.  

“We’re looking very seriously at natural 7-OH and getting that approved,” Trump said. 

It was not clear what Trump meant by “natural 7-OH.” Small amounts of the compound, shorthand for 7-hydroxymitragynine, occur naturally in kratom, which is increasingly used as a recreational drug and an unapproved pain treatment. While kratom is significantly less dangerous than potent synthetic opioids like fentanyl or prescription pain pills, it can still cause addiction and overdose. 

Continue to STAT+ to read the full story…

What Is Traumatic Separation?

You may have a memory of being separated from a parent when you were a child, even just for a few minutes. Maybe you lost them in a crowd or wandered a little too far at the store and felt panicked and afraid.

A moment like this might be among your earliest memories because the feeling was so intense, says Caitlyn Downie, LCSW, the Director of Trauma and Resilience at the Child Mind Institute. That offers some insight into the fear of a child of any age who is separated from a parent or caregiver in a more serious way. The effects of this stress are so powerful they can actually change the way a child develops.

A toddler whose mother goes to prison. A kindergartener whose father is detained and deported. A teen who is placed in foster care. These are a few examples of what experts call traumatic separation, a clinical concept based on the importance of the parent-child bond and the profound effects that can result from breaking it.

What is traumatic separation?

Traumatic separation isn’t a clinical diagnosis, but research shows that it can be profoundly harmful to kids. What makes it traumatic (as opposed to routine partings, like when an adult regularly leaves their child to go to work) is the character of the separation: ones that are sudden, unexpected, or confusing, or those that come about through larger distressing events, like a natural disaster or war. It’s not defined by the time spent apart — both short and long-term separations can be harmful.

Some common examples of separation that can become traumatic include:

  • Parental deportation
  • Immigration (e.g., forced separation at the border)
  • Parental military deployment
  • Parental incarceration
  • Termination of parental rights

Separating from a parent or primary caregiver can be distressing to a child even when it’s deemed necessary for their safety, as in cases where the parent they have been separated from has abused them, says Kimberly Alexander, PsyD, a psychologist at the Child Mind Institute. “There’s still a natural attachment that occurs. And the separation disrupts that relationship, even if it’s for the support and care of the child.”

Why is traumatic separation harmful?

More than eight decades of research has shown the profound developmental importance of the parent-child bond. This is the guiding principle of attachment theory, which was pioneered by a British psychologist who studied children who were evacuated during the Blitz, the aerial bombardment of London in World War II.

Here’s what the research tells us about the harms of traumatic separation:

It can disrupt secure attachment

Think of secure attachment as a “fundamental sense of security and safety” that a child feels with a parent or caregiver, says Dylan Gee, PhD, a psychologist at Yale University who studies how early-life stress affects children’s development.

“Attachment is the lens through which children come to know what they can expect from the world around them,” she explains. “Is this going to be a safe place or a dangerous place? This is foundational to a child’s sense of their ability to navigate the world. Traumatic separation can shatter that sense of safety.”

It can affect neurobiological development

Children’s brains are especially plastic, says Dr. Gee, constantly learning to understand their environment and how to deal with stress. “Trauma that occurs in childhood can be even more consequential than trauma that occurs later in life,” she says, and experiencing these disruptions in childhood can affect the way your brain and body are primed to react to stress later on.

But heightened plasticity is a paradox, she adds. “It confers more vulnerability, but it also confers more potential for resilience — children have heightened potential for supportive intervention and for healing and recovery.”

What do the effects of traumatic separation look like?

There are acute and short-term effects that are common across kids of all ages:

Sleep problems: “It’s often one of the first things that we see: nightmares, trouble falling asleep, or a lot of crying as kids are trying to fall asleep,” Dr. Gee says.

Separation anxiety: This might look like distraction, withdrawal, or clinginess because of fear of being separated from their new caregivers, Dr. Alexander says.

But signs may take weeks or months to show up. Dr. Alexander advises caregivers to consider the child’s baseline — their typical patterns of eating, sleeping, or engaging with others. “If they’re having more trouble with sleep, they’re eating more, eating less, they’re withdrawing or expressing a lot of worried thoughts three or four months later — that’s something worth getting looked at by a clinician,” she says.

Signs of traumatic separation at different ages

“Sometimes people ask, ‘Well, when is separation the most harmful?’ It can be extremely harmful at any age,” Dr. Gee emphasizes. But there are specific signs at different developmental stages:

Infants

Babies may not be as consciously aware of being separated from a parent as older children, “but they’re fundamentally aware that their primary source of regulation and safety is missing,” Dr. Gee says. Because infants are so reliant on caregivers for nurturing and sustenance, the separation “can be experienced as a threat to their survival.” That might look like “crying a lot or becoming withdrawn,” she says. “And at any age we can see intense fear.”

Toddlers and young children (3–6)

Toddlers and young children might become extra clingy with new caregivers or show regressive behaviors like bedwetting or baby talk. Regressive behaviors happen when kids are overwhelmed by stress and can’t express themselves another way, Downie says. “It’s like your nervous system goes kind of haywire,” she explains, “so it uses the body to signal that something is wrong.”

Similarly, kids at this age might act out more, throwing more tantrums, or withdraw. They might develop selective mutism, a condition where kids are too anxious or distressed to speak, even when they want to, in certain situations or with certain people.

School-age children

School-age children might act out or experience separation anxiety. They may also struggle to understand the meaning of the separation, why it happened, or who is at fault for it. Thus, kids at this age are more prone to magical or distorted thinking and feelings of guilt, thinking or saying things like, “I’m the one that caused this” or “This is my fault.”

The weight of these distorted thoughts or other worries, Dr. Alexander says, might make it appear as though a child is struggling to concentrate or that they’re disengaged or distracted. They might withdraw in a group or be averse to stepping outside of their comfort zone.

Children who are school age or older can also experience emotional desensitization — a kind of emptiness of feeling — Downie says, which can look like spikes in irritability, a lack of empathy, not smiling or expressing positive emotions, or an inability to relate to others.

Preteens and teenagers

“I’ve seen teenagers have a lot of mistrust with systems and be very oppositional,” says Downie. “Like, ‘I don’t trust you. I don’t trust my teacher. I don’t trust this child services worker.’” It might make sense that, say, a teen in foster care would be wary of the foster care system. But Downie says it’s often a larger instinct for anger and mistrust, one that extends beyond any specific entity or person.

The teenage years are also when kids are forming their identity, and traumatic separation can fundamentally alter that process. For example, a teen with younger siblings may step into a parent role, taking on new worries and responsibilities. Conversely, teens may become more reckless in a caregiver’s absence, putting them at risk for substance abuse or incarceration.

How to help kids separated from a parent

Adults caring for a child who has been separated from a parent — family members, foster parents, teachers — “can play a profound role in supporting their mental health and resilience,” says Dr. Gee.

Validate feelings

One of the most important things caregivers can do is be present as a child reacts to their experiences, especially if and when scary feelings come up. But be careful not to lead kids or assume they feel a certain way. “You don’t want to make something more distressing to a child if it’s not presenting itself,” says Downie.

If a child expresses guilt, or says something like, “This is my fault,” there are still ways to validate the feeling without endorsing the statement, says Dr. Alexander. You might say something like: “I can understand why that thought comes to mind and how difficult it is to feel that way. When you’re ready, let’s think about other possibilities to this situation.”

Create consistency and stability

One of the hardest things about traumatic separation is the uncertainty — Where did they go? When will they come back? What is happening? Giving kids some sense of consistency and stability can help them feel safe despite the unknowns. So as much as possible, help them stick to any routines: going to school, seeing friends, doing activities they enjoy.

Dr. Alexander advises focusing on things you can control — for example, shielding kids from potentially worrying discussions in a family where a parent has been deported.

“There would likely be a lot of conversations in the home about the situation, maybe a lot of watching the news, maybe making a lot of phone calls to attorneys,” she explains. “So where are you having those conversations, and can you have them in an area or at a time of day where your kid isn’t overhearing the discussions out of context?”

For young kids, it might be as simple as asking them to play in their room. For teens, it might be better to have certain conversations when they are out of the house and invite them to participate directly in others.

Be honest but reassuring

Caregivers might not have all the answers — like knowing when a child’s parent is coming back — but they can create a sense of consistency and stability in how they respond to kids’ questions, too.

Avoid undue reassurance (“Everything is going to be fine”) or over-promising (“They’ll be back in two weeks”) by focusing on what kids can expect, says Dr. Gee. For example: “What I can tell you is that I’m here for you, and I’m going to be with you until he’s back,” or “You’re safe with me, and I’m going to stay with you through this really hard time.”

Model handling stress

Children are sensitive to tone, Dr. Alexander says. “So, if you’re having really big emotions that are out of context for a child, the child is looking at these emotions and trying to understand what’s happening. ‘Am I in danger in this specific moment?’”

She says it helps to have conversations about these moments, especially with younger kids. “Like, ‘I know you noticed mommy crying. We’re feeling really big feelings, and this is how we’re going to deal with those big feelings. I’m going to take a break. I’m going to get a sip of water. Whenever you’re having big feelings, I want you to let me know so that I can help you try doing the same things,’” Dr. Alexander says, explaining the importance of naming the emotion and then teaching kids that there are ways of dealing with it.

Long-term risks of traumatic separation

The effects of traumatic separation can persist even after a child and their caregiver are reunited. Traumatic separation, like other adverse childhood experiences, puts kids at risk for a host of long-term medical and mental health conditions, including depression, anxiety, attention issues, and post-traumatic stress disorder (PTSD).

But Downie notes that not everyone who experiences traumatic separation develops PTSD. “Just because someone’s experiencing trauma now doesn’t mean that it’s going to become a PTSD diagnosis,” she says. “A lot of the behaviors that we’re talking about are normal and expected. There’s an adjustment period when a separation happens.” But if symptoms persist or escalate over several months, a child may need more serious support.

Treatment for a trauma diagnosis

While not every child who experiences a separation may receive a trauma diagnosis or require treatment, cognitive behavioral therapy (CBT) — and the more specific trauma-focused cognitive behavioral therapy (TF-CBT) — is the “gold standard,” says Downie. TF-CBT is specifically for children experiencing trauma-related symptoms. An important component of TF-CBT is creating a trauma narrative, where kids create a story about what happened to help them process it. “But if you have a child who is not ready to process and integrate that trauma, you can’t force the pacing of the treatment,” she says.

In short, a good clinician will follow a child’s lead — even if that means just sitting in the same room with them to build trust. “People really need to feel like they’re being heard and that they can trust someone,” Downie says. Which is why a supportive caregiver or trusted adult can make a big difference.

“If people can take anything away from this, it’s that you want to make kids understand that that they’re not responsible for what’s happened and that people do care about them,” Downie says. “Kids are really resilient, and they can adapt in a good-enough environment. They don’t have to have everything to be successful.”

The post What Is Traumatic Separation? appeared first on Child Mind Institute.

<![CDATA[Psilocybin therapy shows fast, lasting relief for depression; clinicians discuss trial hurdles and emerging promise for PTSD and addiction in this podcast.]]>

Digital Therapeutic Content for Substance Use Disorder Treatment: Development and Evaluation Study

Background: Substance use disorders (SUDs) are a major public health concern, contributing to significant individual and societal costs. Despite this, the uptake of evidence-based pharmacologic and behavioral interventions remains limited. The digital delivery of SUD treatment has emerged as a potentially scalable way to reduce access barriers and increase treatment use. Existing digital therapeutic interventions are often created without clinician involvement, evidence-based materials, interdisciplinary input, or content review. The implementation of a structured and methodologically rigorous development process is needed across digital health interventions to help ensure patient-facing materials are validated, understandable, and actionable for the end user. Objective: This early report seeks to describe and evaluate an iterative, interdisciplinary, platform-agnostic process for adapting and refining existing print materials for digital therapeutic modules in SUD treatment. The a priori goal was to evaluate if a structured, human-centered approach would generate digital modules that were rated as understandable and actionable based on a validated assessment for written materials. Methods: Fourteen therapeutic modules were adapted from existing Mayo Clinic–written, patient-facing education materials originally developed by a board-certified addiction psychiatrist and a doctoral-level education specialist for clinical use. A team of 4 purposively recruited licensed alcohol and drug counselors with lived experience with a SUD, all in recovery, and a doctoral-level therapeutic specialist met weekly for one hour over a 6-month period to iteratively adapt this existing content for smartphone delivery (2‐3 hours per module). The process flow included selecting source material, restructuring content for viewing on a phone screen, simplifying language, improving organization and flow to promote understanding, and including specific actions users could take based on the content. The counselors then independently evaluated the modules using the Patient Education Materials Assessment Tool for printable materials (PEMAT-P). PEMAT-P scores for understandability and actionability were calculated as percentages, and descriptive statistics were used to summarize scores in aggregate and across modules. A target of >70% was set for each PEMAT-P domain, consistent with accepted benchmarking standards. Results: Mean understandability and actionability for all modules were 87.2% (SD 4.8%; range 81.4%‐96.9%) and 75.1% (SD 12.3%; range 57.1%‐95.0%), respectively, exceeding the recommended threshold. While all modules were adequately understandable, 35.7% (5/14) scored below the actionability threshold. Conclusions: This early report highlights the value of a human-centered, iterative process for adapting therapeutic materials for digital delivery in SUD treatment. Although the modules performed well overall on PEMAT-P benchmarks, actionability was less consistent than understandability, and aggregate scores masked weaknesses in several individual modules. This indicates that a standardized process does not guarantee actionable material across all content types. Involving current patients in this process may improve the end product by incorporating a perspective that was previously missed.

Oral Small-Molecule GLP-1s Linked to Deep Brain Activity and Reduced Cravings in Mice

Interest in glucagon-like peptide 1 receptor agonists (GLP-1s) continues to surge due to their effectiveness in reducing body weight and improving metabolic outcomes. This includes interest in small molecule oral GLP-1s which are more bioavailable and more easily manufactured than their injectable counterparts.

Now data from a new study in mice performed by scientists at the University of Virginia shows that this emerging class of weight-loss drugs suppress hedonic eating by modulating a reward circuit deep in the brain that is separate from previously described mechanisms that broadly affect appetite. The scientists believe that this pathway could be an avenue by which GLP-1s treat other dysfunctions in reward processing such as substance use disorders.

Details of the National Institutes of Health-funded study were published this week in a Nature paper titled “A brain reward circuit inhibited by next-generation weight-loss drugs in mice.” In it, the team reported that they investigated the small-molecule GLP-1s including Eli Lilly’s recently approved drug orforglipron, also known by the brand name Foundayo, as well as danuglipron, an oral GLP-1 that was being developed by Pfizer until the company decided to discontinue its development in 2025. 

Previous studies that explored the effects of larger peptide GLP-1s such as semaglutide in the brain have found that they suppress hunger-driven eating by engaging networks in the hypothalamus and hindbrain. What has been less clear is the mechanism by which small-molecule GLP-1s work. “As the accessibility of these medications continues to rise and patient uptake increases, it’s crucial that we understand the neural mechanisms underlying the effects we’re seeing,” said Lorenzo Leggio, MD, PhD, clinical director of NIH’s National Institute on Drug Abuse.

The current study gets scientists one step closer to that goal. According to the paper, the scientists first used gene editing to modify the GLP-1 receptors of mice to make them more humanlike. They then administered orforglipron or danuglipron to the mice, and identified brain regions where the drugs induced activity. The results showed that in addition to inducing activity in familiar pathways, the drugs also triggered the central amygdala, a region associated with desire that is deeper in the brain than scientists previously thought GLP-1s could directly reach. Further testing showed that once activated, the central amygdala reduced the release of dopamine into key hubs of the brain’s reward circuitry during hedonic feeding. 

“We’ve known that GLP-1 drugs suppress feeding behavior driven by energy demand,” said co-corresponding author Ali Guler, PhD, a professor of biology at the University of Virginia. “Now it seems oral small-molecule GLP-1s also dial back eating for pleasure by engaging a brain reward circuit.”

Given the effect of these drugs on eating for pleasure, future studies could explore whether small-molecule GLP-1s can also suppress cravings for other addictive substances. It is a question that the team hopes to explore in follow up studies focused specifically on substance use disorder. 

The post Oral Small-Molecule GLP-1s Linked to Deep Brain Activity and Reduced Cravings in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.