What happens when you ask thousands of people about trauma instead of trying to fit them into a diagnostic box? Kerry found that nobody fit the DSM—everybody had everything. Once he started asking specifically about trauma, he discovered it was everywhere, hiding beneath substance use, depression, and anxiety. He began thinking about trauma the way physicians in the 1800s thought about syphilis—a hidden driver behind conditions we were attributing to something else entirely.

That observation led him deep into the neuroscience of fear memory: how it forms, whether it can truly be extinguished or only suppressed, and whether the hours and days immediately after a traumatic event represent a critical window—like the window we exploit after a heart attack or stroke—to prevent chronic PTSD before it takes hold. And it raises a question that is as much ethical as scientific: if we could dampen the emotional weight of a traumatic memory, should we?

We close with Kerry’s hard-won optimism that as neuroscience and psychiatry converge, more personalized and effective treatments for fear and trauma are finally within reach.

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This podcast is for general educational and informational purposes only. Sensorium’s compounds are investigational and have not been approved by the FDA for any use; nothing discussed here should be taken as a claim about their safety or efficacy. The views of any guests are their own and do not represent Sensorium. Nothing in this podcast is medical, legal, or investment advice, and nothing here is an offer to sell or a solicitation of an offer to buy any securities. Statements about future plans, timelines, or outcomes are forward-looking, reflect current expectations only, and are subject to change.

Her work traces psychiatry’s recurring pivots. The field abandons one framework for another, convinced this time it has found the real source of mental suffering. What makes Anne’s perspective invaluable is her refusal to let any single story win. Mental illness doesn’t map neatly onto what we call disease. Yet we’ve narrowed our response almost exclusively to medical intervention.

The question she keeps returning to cuts deeper than methodology. What matters most—getting the label right, or addressing the suffering? Should we wait to name something until we see what intervention actually helps? And why have we decided that only one domain of expertise should be involved when the human brain is profoundly social and hardwired to consume symbols and meaning?

This is a conversation about what we’re really trying to solve—and whether science alone can get us there.

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This podcast is for general educational and informational purposes only. Sensorium’s compounds are investigational and have not been approved by the FDA for any use; nothing discussed here should be taken as a claim about their safety or efficacy. The views of any guests are their own and do not represent Sensorium. Nothing in this podcast is medical, legal, or investment advice, and nothing here is an offer to sell or a solicitation of an offer to buy any securities. Statements about future plans, timelines, or outcomes are forward-looking, reflect current expectations only, and are subject to change.

Bryan’s path to neuroscience began with his mother’s schizophrenia and his sister’s experience with LSD—experiences that set a teenager on a lifelong quest to understand how molecules change minds. Decades later, he finally saw what he’d been chasing since he was 14: the crystal structure of LSD bound to a serotonin receptor. “We had a lab meeting, and they showed it, and I started weeping. This is what I’ve been chasing my entire life.”

What makes Bryan remarkable isn’t just the breakthroughs—it’s his ability to hold paradoxes lightly where others see rigid boundaries. He moves seamlessly from Zen meditation to receptor pharmacology, from the molecular to the existential. And his take on mental health research is characteristically provocative: “We’ve been doing an uncontrolled chemical experiment on the entire human population for millennia.”

This is a conversation about pure scientific passion—and why understanding the brain might require us to quiet our own minds first.

Jerry’s journey began in the 1970s as what he calls a “rogue trainee”—one of the first to embrace psychopharmacology when giving patients “chemicals” was considered radical. From those controversial beginnings, he helped build what became a network of 50-60 specialized clinical and research programs at MGH.

His framework for understanding our current moment is both elegant and unsettling: anxiety, he says, is spreading like an autoimmune disease—a protective system now turned against us, keeping us in a state of arousal that limits our possibilities as humans.

This is a conversation about psychiatry’s hard-won wisdom and the molecules nature left for us to discover.

The views expressed in the discussion are Dr. Rosenbaum’s personal perspectives based on his decades in psychiatry and do not represent statements about Sensorium Therapeutics’ investigational products or development programs.

Ever watch the show Hot Ones on Youtube? I don’t think I could handle the heat of those wings even knowing that it’s all a trick of biology! The fiery compound in those hot sauces is capsaicin and it activates a “heat receptor” in your nervous system (TRPV1), even though no actual heat is present. That receptor evolved to detect dangerous temperatures — but plants hijacked the system. I learned from (you guessed it) wikipedia that birds’ version of TRPV1 does not respond to capsaicin. Wow! Evolution made sure that the seeds could be eaten and spread by birds but not mammals! Clearly there must have been some evolutionary pressure to cover long distances. Co-evolution can be sophisticated!

[So does menthol actually hit a “cool” receptor? YES! check out TRPM8].

Hijacking the “heat” and “cool” receptors are just the beginning of the “illusions” in your mind! The interpretation of molecules interacting with our bodies by our brains is remarkably shaped outside of the “self”. That is, there is a clear, and quite extensive interplay between human experience and nature — obvious right? What I mean though is that where human and nature each begin and end is actually really blurry! When your nervous system reacts to plant molecules, it's not because the molecules evolved for you or in you. It’s because you and those molecules ended up navigating the same biochemical universe — and sometimes, the paths converged. (I use “you” loosely here to mean your evolutionarily encoded past.)

By the way… caffeine is an insecticide that just so happens to keep you awake.

You think coffee and tea are for you? Nature’s gift to humans? Well, sort of. Caffeine didn’t evolve to wake up humans — not much of an evolutionary advantage unless human cultvation after a morning cup of joe was a solution to environmental pressures on arabica. I think more likely is that plants figured out how to engineer a neurotoxin to paralyze insects that chew on plants. And yet, in humans, that same molecule antagonizes adenosine receptors in the brain — making us feel alert and focused. That overlap — between a molecule’s function in a plant and its unexpected effect on a mammalian brain — isn’t just pharmacological coincidence or some twist of luck. This is what I’ll call “chemical evolutionary convergence”. Different evolutionary lineages arrived at similar (or the same) biological tools for survival, whether in this case to defend against predators or regulate a sleep-wake cycle.

Many receptors in the human brain — for pain, pleasure, mood, attention — are sensitive to molecules produced by organisms that don’t have a nervous system at all. I find that fascinating. Take the opioid receptors, for example. They interact with endogenous peptides like endorphins (think runners’ high), but also plant alkaloids like morphine. Why would these “foreign” molecules fit and modulate the receptor in the human brain so well? One explanation is that over evolutionary time, animals that interacted with certain plants may have adapted receptor systems to modulate or respond to those exposures. Another explanation is convergent evolution: molecules from entirely different systems that nonetheless “discover” the same functional chemistry.

For most of vertebrate evolution, brains have been surrounded by — and influenced by — chemical ecosystems: plants, fungi, bacteria, and other animals. Many of the small molecules we now call “neuroactive” didn’t originate in neurons. They came from soil microbes, bitter leaves, or toxic roots. Over time, brains became expert at reading and responding to these chemical signals — sometimes defensively, sometimes adaptively. In a sense, your brain is a chemical interpreter of its environment, constantly translating molecules into meaning. Perhaps there was an evolutionary advantage to early nervous systems that could make these neuromodulatory molecules that were otherwise coming from the environment. Perhaps it was co-evolution? Maybe convergent evolution?

You may think this is strange, but look at how many branches of the phylogenetic tree have eyes (maybe 10) and these did not come from their common ancestors. This is the text book example I was taught when introduced to convergent evolution. But convergent evolution isn’t limited to eyes — not at all. Convergent evolution happens at all levels of the organism — even at the level of small (drug like) molecules. Two completely unrelated species may evolve compounds that bind to the same receptor, activate the same pathway, or produce the same behavioral effect.

Biology returns, again and again, to the ideas that work. Chemical evolution, like natural selection more broadly, is a process of finding and re-finding functional solutions with molecules that tune our biology. Understanding chemical co-evolution isn’t just about appreciating nature’s cleverness — clever as she may be. Chemical co-evolution reframes how we think about drugs, consciousness, and the porous boundaries between “natural” and “synthetic.” Many of our most powerful medicines were never meant for us. Yet they work — often exquisitely — because brains and molecules have been sharing an evolutionary stage for a very long time. (As noted in another of my substack posts - 85% of CNS drugs come from naturally occuring compounds.)

For those of you that don’t know, I co-founded Sensorium Therapeutics because I believe we have barely scratched the surface of how to take advantage of this idea of chemical co-evolution between our brains and nature. Co-evolution shaped how we sense, feel, suffer, and heal. Maybe we can decode the language that connects nature to our brains in pusuit of that last bit — healing. The world sure seems to need that right now!

In Eleusis, ancient initiates drank something called kykeon, a mysterious brew that may have contained psychedelic compounds like ergot alkaloids. As I understand it, these folks weren’t chasing euphoria. They were confronting death through the major frame shifts in the human brain/mind—and coming back from the experience changed. Plato, Cicero, and even early Christians seem to have partaken. It certainly wasn’t fringe. The book walks through the fascinating birth of Christianity through this lens and postulates that the early sacraments of Christianity may have been the same as, or similar to, the kykeon.

I find it fascinating to imagine times in the ancient world, but also maybe not that long ago when the line between science and religion was blurry (if it existed at all). You might be surprised to know that Newton (early 1700s), considered the father of classical physics, spent most of his time studying alchemy and biblical prophecy. He described nature’s laws as a way to record the devine codes.

Even more recently, (late 1800s) at the dawn of modern psychology, philosopher William James turned to mystics, spiritualists, and religious ecstatics—not patients in clinics—for insight into consciousness and mental health. He famously took nitrous oxide and recorded its effects, not dismissing them as delusion but rather describing them as doors into altered states of mind. In his Varieties of Religious Experience, James argued that mystical experiences, however irrational, were psychologically real—and in fact, often healing.

Best I can tell, things really started to shift in the 1950s when patients being treated for tuberculosis with a drug called iproniazid began reporting unexpected mood elevation. This wasn’t placebo—many became more energetic, hopeful, even euphoric. The drug turned out to inhibit an enzyme called monoamine oxidase (MAO), which breaks down neurotransmitters like serotonin, dopamine, and norepinephrine. After a few related discoveries, an idea emerged: What if depression is caused by too little serotonin or norepinephrine? [I’m still trying to track down who to most attribute this idea to.]

By the 1980s and 1990s, with the rise of selective serotonin reuptake inhibitors (SSRIs) like Prozac, pharmaceutic companies were eager to differentiate and market their products and they embraced (and promoted) the idea that disorders like depression and anxiety were simply the result of neurotransmitter deficits. The "chemical imbalance" narrative helped reduce stigma for some—it offered a medical explanation rather than a moral judgment. But it also flattened complexity, turning a richly human experience into a serotonin shortfall.

If you’re old enough you might remember the “sad blob” commerical. If you’re not, it’s worth a quick watch. (There’s a nice article here about its history and evolution if you’re curious.)

Even as a chemical neuroscientist, I believe the mind is more than chemistry—and healing it requires more than simply correcting neurochemical imbalances. That said, chemistry can be a powerful catalyst. It can help lift us out of local energy minima—a shift some might recognize as neuroplasticity in action.

We have a lot to learn about the brain and the mind (understatement of the year?). I believe strongly that powerful neurochemicals (i.e. drugs) are great tools for learning. I also believe that Mother Nature is the most gifted chemist. Thus, returning to the neuroscience of our ancestors is a “no-brainer” for me.

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