STAT+: Another big deal, another sign biotech M&A is back

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Good morning! Pharma companies are on a biotech buying spree, an LSD pill just delivered unusually strong late-stage depression data, and the FDA reverses course of Regenxbio’s treatment.

Also: Today, thousands of industry players (and me!) are gathering in San Diego for BIO to talk deals, science, and whatever comes next. Check out the last item for a jaunt down memory lane about the conference.

Continue to STAT+ to read the full story…

STAT+: Definium LSD therapy helped patients with major depression in late-stage trial

Definium Therapeutics said Monday that its LSD therapy significantly helped patients with major depression in its first Phase 3 trial, bringing the psychedelic drug closer to a potential approval.

Six weeks after a single dose, patients on the pill, called DT120, experienced a 13.3-point drop on a depression test called the Montgomery-Åsberg Depression Rating Scale (MADRS), compared with a 5.2-point drop among patients taking placebo.

By 12 weeks, the effect waned a bit but was largely maintained, as patients on the pill had an 11-point drop from their baseline, compared with a 3.6-point drop in the placebo group.

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Prevalence and Predictors of Self-Reported Adverse Experiences in Digital Meditation Training: 2 Randomized Controlled Trials

Background: Digital meditation-based interventions (MBIs) reach vast global audiences with millions of active users, yet concerns persist about the frequency and nature of adverse experiences (ie, AExs) occurring during meditation training. Some researchers have argued that AExs are substantially underdetected and reflect iatrogenic harm caused by meditation (ie, adverse effects [AEfs]). Others contend that these experiences largely reflect common stressors that would be experienced without meditation. These competing perspectives underscore the need for further research, particularly in the context of digital MBIs, the most widely used form of meditation training. Objective: This study examined the prevalence, predictors, and subjective evaluations of AExs during a digital MBI and tested whether reported experiences may be caused by meditation practice via comparisons between meditation-exposed and nonexposed participants. Methods: Data were drawn from 2 trials of the Healthy Minds Program. Exploratory study 1 (n=315) consisted of a sample of distressed US undergraduate students to estimate the prevalence of AExs and identify baseline predictors. Preregistered confirmatory study 2 (n=594) sampled distressed US adults from all 50 states to replicate findings from study 1 and to examine participants’ subjective evaluations of AExs. Study 2 additionally compared AEx rates between participants who did and did not complete guided meditations to assess whether AExs could be caused by meditation exposure. Study 3 (n=87) used qualitative methods to analyze study 1 participants’ responses to an open-ended question regarding their strategies for coping with AExs. Results: In studies 1 and 2, 27.9% (88/315) and 10.1% (40/396) of participants, respectively, reported at least one AEx during the study period, with 6.7% (21/315) and 3% (12/396) reporting functional impairment, largely aligning with previous research. Critically, in study 2, rates of AExs did not significantly differ between participants who did and did not complete guided meditations, suggesting that these experiences were not caused by meditation practice. Higher baseline depression, anxiety, loneliness, experiential avoidance, and perceived barriers to meditation predicted more frequent AExs. In studies 1 and 2, 89.8% (79/88) and 90% (36/40) of participants who reported AExs, respectively, indicated that they were glad to have learned to meditate. Qualitative analyses showed that participants used diverse coping strategies, often using skills learned through the Healthy Minds Program. Conclusions: AExs were relatively common but occurred at comparable rates among participants who did and did not meditate, challenging claims that such experiences were caused by meditation practice in distressed individuals. Although a small subset of participants reported some degree of functional impairment, most evaluated their AExs as tolerable and described their overall MBI experience as positive. Together, these findings highlight the importance of distinguishing AExs that likely reflect epiphenomena of preexisting distress or symptoms from iatrogenic harm attributable to MBIs. Trial Registration: Study 1: ClinicalTrials.gov NCT04741529; https://clinicaltrials.gov/study/NCT04741529; Study 2: ClinicalTrials.gov NCT06282523; https://clinicaltrials.gov/study/NCT06282523
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Inside interoception: The hidden sense of how you feel inside

MIT Technology Review Explains: Let our writers untangle the complex, messy world of science and technology to help you understand what’s coming next. You can read more from the series here.

Your brain lives in the dark space of your skull. Yet it knows when the wind lifts the hairs on your skin, when your heart is racing, when your gut tightens with fear.

It’s also, right now, predicting what you’ll read next as your eyes move across this page. It’s picking up signals that help it make sense of what’s happening around you and prepare you to act if you need to stay safe. You aren’t usually aware that your brain is doing all that.

Our senses take in information at a staggering rate—roughly 11 million bits flood in every second from our skin, eyes, ears, and more. That’s nearly three paperback novels’ worth of data every second. Only a sliver reaches our conscious awareness.  Researchers estimate that our conscious minds can process roughly 10 to 60 bits of information per second, about the rate at which you’re reading this sentence. That’s a ratio of about one conscious bit to hundreds of thousands of unconscious bits.

And that’s a mercy. As Moriah Thomason, a neuroscientist at NYU Langone, says, “Thank goodness we’re built like this. There’s a layer of what we have access to in conscious awareness. And then we have a right-under-the-surface amount. There is only a certain amount we are meant to ‘hold in mind’ in order to function successfully.” 

What you are aware of: Your stomach growling when you’re hungry. Your palms sweating before you speak in public. The breath you just took, if you pay attention to it. Even your heartbeat, which some people can sense from the inside without feeling their pulse in their wrist.

Scientists have a word for how we sense ourselves from the inside: interoception. 

The term was coined in 1906 by the British neurophysiologist Charles Sherrington. For most of the 20th century it remained largely confined to textbooks. Today, thanks to a 2021 Nobel Prize and new tools that can map the interoceptive system across the body, the study of this facility is suddenly quite hot. As researchers decode how signals move between body and brain, a clearer picture is starting to take shape—with implications for how we understand and treat conditions from obesity to chronic pain to anxiety.

The field began to take off in the 1990s. In 1994, the neurologist Antonio Damasio published a book with a pointed title: Descartes’ Error. He challenged the historical separation of thinking and feeling, arguing that our ability to choose and act is driven by feelings, and those feelings in turn are shaped by the body’s signals, such as your gut clenching or your skin going clammy. When we lose that connection between feeling and thinking, as one of Damasio’s patients did after surgery to treat a brain tumor, we may still be able to reason with perfect logic about the pros and cons of traveling on a Tuesday or a Wednesday. But without the emotional signals that help us predict what a choice will feel like, our reason spins and circles, and we cannot decide.

A contemporary of Damasio’s, the neuroscientist Bud Craig, spent his career asking one question: How do you feel? He charted how the brain builds an inner map of the body and updates it in real time every moment you are alive.

Think of the captain’s bridge on the USS Enterprise, where a live map displays the status of the ship’s critical systems: oxygen levels, energy availability, hull integrity, shield strength. Another set of indicators senses things outside the ship: asteroid belts, enemy ships, radiation, life signs, and spatial anomalies not yet understood.

Your brain, only about the size of your two fists pressed together, creates a map like this for your entire body, along with a map of the outside world, from data streaming in through your five senses. Together, they feed into your brain’s working model of you in the world, now and across time—where you are, who you are, your expectations for what’s about to happen (based on everything you know), and what all that means for you.

When someone asks “How are you doing?” we consult our maps and report back on our status. We might say we’re happy, depleted, anxious, or energetic. These feelings are always a braid of emotional and physical sensations. They’re what your interoceptive navigational system serves up to your awareness when you sense yourself from the inside.

As we grow up, we learn to interpret what these sensations mean—interpretations that, in turn, can alter our physiology, emotions, and behavior. Research by the psychologist Alia Crum shows that people who embrace a “stress is enhancing” mindset produce more growth hormones than people who have a “stress is debilitating” mindset. They also experience more positive emotions and greater cognitive flexibility.

Language also matters. We learn words for the textures of our feelings—words that then shape how we feel and act. People low in emotional “granularity”—as the psychologist Marc Brackett calls the ability to distinguish between closely related feelings—react more impulsively under stress and are less able to find meaning in difficult experiences. But mindsets and emotional intelligence are malleable. We can learn that “anxious” is different from “terrified,” and we can even reframe how we interpret our body’s sensations. Instead of thinking of the butterflies in our bellies as annoying, we can welcome them as our body’s way of preparing us for a peak performance.

Scientists have long understood that the interoceptive information informing these lived experiences travels via two major systems: nerves and humors (blood and lymph). Now they’re actively studying a third system—the “interstitium,” a network of fluid-filled spaces woven throughout the body’s connective fascia that may also play a role in communication.

But until recently, scientific understanding of this interoceptive system looked like a high-level schematic that left out vital details—how information travels from the outside environment in, how it moves from your body to your brain, and how it is integrated and interpreted within your brain. Researchers are now racing to explore what the neuroscientist Catherine Tallon-Baudry calls this “new continent of awareness.”

The wandering highway

One of the most active areas of research centers on the vagus nerve, the main component of the parasympathetic nervous system and an information highway carrying news from your organs up to your brain and back down to your body. The vagus has become a celebrity nerve, ubiquitous in wellness podcasts and trauma therapy. “Tone your vagus nerve.” “Activate your parasympathetic system.” The language suggests a single thing you can target, like a muscle. The reality, as Steve Liberles at Harvard Medical School is discovering, is far more interesting.

Liberles has spent most of his career mapping what he calls “the great wide unknown” of one of our largest and longest nerves. He speaks the way he works—methodically, without overselling. But the questions driving him are huge. How do we sense our body’s inner state? What information flows through which channels? And how does the brain decide what to do with it?

“When I’m nervous giving a talk in front of a thousand people,” he says, “my heart might race. I might get butterflies in my stomach. I might get goosebumps on my skin.” We all know what he’s talking about.

“It’s bizarre,” he muses. “Your brain has to send a signal to the gut, and then the gut back to the brain, to tell you you’re nervous?” He pauses. “This just shows there is this intimate connectivity between the brain and the body that’s real.”

The vagus is often called the calming nerve, because it controls “rest and digest” functions that quiet our body after the sympathetic nervous system revs us up with “fight or flight” impulses to handle danger or stress. 

But it is also doing something else: It’s listening to us inside. Anatomists have known for over a century that roughly 80% of its fibers carry information upward, from body to brain. Think of it as a two-lane highway with far more traffic headed north. What scientists are just beginning to understand in detail is what those signals are saying. 

Liberles is decoding the vagus with molecular precision and finding that its messaging system is unexpectedly diverse. So far, his research has uncovered dozens of types of vagus nerve cells, each wired to a specific organ. Team Red relays information about the heart; Team Blue, the gut.

Within those teams, each courier has a unique job that’s different from those all its teammates perform. Liberles found 10 types in the lungs alone. Until then, only one lung reflex had ever been identified, in 1868. One nerve courier carries information about breathing rate; another the stretch of your lungs; yet another information about airway threats, like food going down the wrong pipe.

“It’s super exciting to think about what each of these neurons is doing,” he told me in a conversation last fall, a flash of intensity breaking through the calm. “Where does it go in the body? What is it sensing? What is it controlling?”

The doors of the cell

Liberles is mapping the vagus information highways. But highways need on-ramps for signals to enter. For years, one of neurobiology’s biggest mysteries was the molecular on-ramp for our sense of touch.

Somewhere, something in our bodies was converting physical force into an electrical signal that the nervous system could understand. But no one knew how. 

Solving that mystery required a scientist willing to trust a hunch when the data couldn’t show the way. 

Ardem Patapoutian grew up in Lebanon and fled the country’s civil war at 18, landing in Los Angeles, where he delivered pizzas and wrote horoscopes for a local newspaper before falling in love with science at UCLA.

In the 1990s, as a postdoc at the University of California, San Francisco, he became fascinated with our sense of touch—the last of the five major senses not yet understood at the molecular level. The lung stretch signal that Liberles’s vagus neurons carry to the brain? No one had ever figured out how that signal began.

“How do you feel the embrace of a loved one? How do your fingers distinguish one texture of hair from another?” Patapoutian invites us to wonder in his 2021 Nobel Prize lecture. The problem: Most cellular communication works through chemistry. But mechanical force offers no molecule to bind. How does the body translate physical pressure into the electrochemical language that neurons speak?

Scientists knew that the answer had to be an ion channel—a protein gate embedded in cell membranes that opens to let electrically charged particles into the cell. But tracking down the one responsible for touch turned out to be absurdly difficult. Ion channels are a hundred thousandth the size of a cell, invisible to ordinary microscopes. Worse, they don’t resemble each other. You can’t recognize one by its shape or its sequence of amino acids. Even with one right in front of you, nothing would tell you it was there.

At Scripps, where he works now, Patapoutian decided to try an unusual approach. He’d try to find cells that showed sensitivity to touch and destroy their internal genetic blueprint one gene at a time—hunting for the move that would make the cell go numb. It was tedious, expensive, and possibly a dead end. “A lot of people made fun of us,” he says.

Two years in, Patapoutian’s collaborator Bertrand Coste had burned through half his postdoctoral appointment with no results. Patapoutian said: Another 30 genes, and then we decide whether to continue.

What kept them going, Patapoutian told me, was informed intuition. “As you gain more experience, you have this sense of what’s going to work, what’s not going to work. Sometimes the data cannot answer the question of when to stop or when to continue. There has to be another process. If you start trusting it, it gives you an avenue to continue.”

Coste knocked out candidate gene 72. Flatline. The cell had gone numb.

They’d found it—the mechanism behind something you feel every day.

They named the protein they identified PIEZO, from the Greek piezi, meaning pressure. There are two variations, PIEZO1 and PIEZO2, each responsible for sensing different kinds of pressure in the body. They’re elegant in their design—over 2,500 amino acids folded into a three-bladed propeller-shaped gate embedded in cell membranes. When pressure stretches the membrane, the gate opens and electrically charged ions flood through, translating physical pressure into an electrical signal that the brain can understand—all within milliseconds.

Patapoutian calls scientific discovery a dream that survives reality. He won the Nobel Prize in medicine in 2021 for his discovery of PIEZO, sharing the award with David Julius of UCSF for his work on how cells sense temperature. Now researchers are finding PIEZO proteins everywhere—skin, organs, blood vessels, and even red blood cells, where they help the cells squeeze through narrow capillaries. They’re how your brain knows where your hand is in space without looking at it, a sense called proprioception. They’re in plants too, enabling roots to sense pressure as they push down into the earth.

PIEZO was just the beginning. With a $14.5 million grant from the US National Institutes of Health, Patapoutian and his collaborators are now mapping the body’s entire interoceptive system—as many internal senses as he can find, he says.8

Patapoutian has translated his discovery into a unique form of public outreach. At scientific conferences, he sometimes rolls up his sleeve mid-lecture to reveal half his arm covered in ink—a gigantic PIEZO protein in exquisite anatomical detail, its blades spreading across his biceps. Then he flexes. The tattoo flexes with him, the structure bending exactly as the real protein does when pressure opens the gate.

“At a pub or a party,” he explains, smiling, “how else would I demonstrate this beautiful structure?”

Orchestrating the field

Steve Liberles is mapping a major interoception highway. Ardem Patapoutian discovered the gates of touch. Meanwhile, Wen Chen at the National Institutes of Health is pulling the field together, putting neuroscientists, immunologists, physiologists, and clinicians into the same room. The demand, she says, has been enormous.

She tested her pitch at a dinner party with NIH colleagues a few years ago. You’re hungry right now—that’s interoception. You’re thirsty—that’s interoception. Heads nodded as she pointed around the table.

“We can’t have just the brain or just the body,” she told me. “We need to look at the whole person.”

In 2018 she organized a symposium on interoception where Liberles was one of the invitees, along with researchers and practitioners of meditation and yoga. “It was not their thing,” she says, laughing as she recalls how uncomfortable some of the researchers looked. But the practitioners were excited to finally meet scientists who were studying the inner mechanisms of what they did.

That was followed by a series of NIH workshops on interoception that spanned topics from basic science to clinical practice. Patapoutian was the keynote speaker for the first one. 

The NIH began funding scientists to chart the neural circuits of interoception and bringing them together to talk about their findings. Partway through one of these meetings, the equipment failed for an hour. More than 1,000 people stayed online, waiting for it to come back.

“We were shocked at the turnout,” she says. “There was much bigger interest than we could have imagined.”

Chen is now building infrastructure to match the demand: a formal community, funding mechanisms, a venue where cardiologists and neuroscientists and clinicians can all find each other. And she’s redefining the field as she goes; interoception is not a one-way signal from body to brain but a continuous two-way communication system, each direction shaping the other in real time.10   

Liberles’s nervousness on stage is that two-way loop in action. Signals from his racing heart and belly butterflies travel up to the brain, which weaves them into an interpretation: This is anxiety, and this is what to do to handle it. His actions produce fresh signals that the brain reads in light of its ongoing predictions about what will happen next. In the body-brain communication loop, each player constantly updates the other.

I asked Wen what her work on interoception might mean for another inner sense: intuition. “People talk about ‘gut feelings,’” I said. “How does that relate to interoception?”

 “Intuition might be the bridge where interoception moves from unconscious processing to conscious awareness,” she answered. “If that’s true, then intuition is not magic. It’s physiology.”

But it depends on how we read the signals. Intuition is like pain. It tells you something, but it’s not always clear what. “Perhaps we can treat intuition as a source of data,” she says. “Meaningful, but probably not complete.”

“Maybe we can be grounded in both—in feeling and fact.”

Which raises a more personal question: What do you do with the signals your body is sending?

One avenue for exploration is therapeutic intervention—both pharmacological and neural stimulation. Vagal nerve stimulation has treated epilepsy and depression for four decades, but as Liberles puts it, it’s like pressing all the keys on the piano to hit one note. Weight-loss drugs like Ozempic act in part through vagal pathways but can cause nausea as a side effect, because the targeting isn’t precise enough. Map the body’s circuits with enough accuracy and you might hit the note you actually want.

Another area of active research is psychological and behavioral—teaching people how to detect and even shape interoceptive signals. Low interoceptive awareness is linked to mental-health disorders and stress-related physical conditions.11 But like emotional intelligence, it’s not fixed. Researchers are finding that people can boost their body awareness by, for example, learning to detect their heartbeats from the inside—now a common measure of interoceptive awareness.12 Other interventions focus on body-based therapies and conscious activation of the parasympathetic “rest and digest” system to improve emotional and physical well-being. The placebo effect is another example of the mind acting on the body through expectation alone.

The signals we once dismissed as vague feelings—when your gut tightens before you know why, when your body says yes or no before your mind catches up—those are real. How we interpret them and whether we act on them is another frontier.

It’s clear that gut feelings play a role in scientific research, especially when the path forward looks foggy. Patapoutian’s informed intuition kept him and his colleagues going long enough to find PIEZO, a reminder that major discoveries often start with a hunch that is later tested against evidence. Chen puts it well: Maybe we can be grounded in both feeling and fact.

Katherine W. Isaacs is a writer and senior lecturer at the MIT Sloan School of Management. Her teaching and research focus on the intersection of psychology, technology, and innovation. Originally trained as a biologist and later as a social psychologist, she is currently working on a book called Gut Feel, about intuition, interoception, and embodied decision-making.

The therapeutic role of self-transcendence in moral injury recovery: theory, mechanisms, and clinical implications

A growing body of psychological and neuroscientific research suggests that moral injury (MI) involves maladaptive self-referential processing, including disruptions in moral identity, rigid negative self-appraisals, and impaired meaning-making following exposure to potentially morally injurious events (PMIEs). Building on Mindfulness-to-Meaning Theory (MMT), this paper proposes self-transcendence (ST)—a metacognitive state characterized by reduced self-focus, expanded awareness, transcendent affect, and prosocial meaning—as a potential mechanism for MI recovery. Within MMT, mindfulness practice is theorized to cultivate ST via decentering and meta-awareness, processes that broaden attentional scope, promote flexible cognitive reappraisal, and modulate habitual self-referential processing. Mindfulness and contemplative research further link ST to increased cognitive flexibility, reduced in shame-focused narrative self-processing, and adaptive integration of emotionally and morally disruptive experiences. Drawing on an integrative review of ST-consistent and MI-related mechanisms, this paper argues that fostering ST through mindfulness-based and contemplative practices may reduce rigid self-focus, expand interpretive frameworks of meaning, and support moral identity repair and meaning-making. Implications are discussed for designing interventions that intentionally cultivate ST as both standalone approaches and modular components, while acknowledging current limitations in measurement, readiness assessment, and the reliable induction of ST states.
<![CDATA[Explore 2026’s fast-moving psych med pipeline: new Alzheimer agitation option, potential novel ADHD therapy, and promising psilocybin for depression.]]>

Opinion: How the military may be fueling eating disorders in men

As a yoga instructor in a clinic for people with eating disorders, I don’t see many straight cisgender male clients. But when I do, many have one thing in common: military service.

It is so common that, anecdotally, I would say a military background is one of the greatest risk factors for eating disorders in this population. Indeed, troops and veterans experience eating disorders and disordered eating at higher rates than civilians. For example, veterans have bulimia at rates about three times higher than civilians. Many of the male service members and veterans I work with feel their bodies will never be lean enough, strong enough, or “combat-ready” enough.

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