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Dillan DiNardo thinks the term "psychedelic" is nothing more than a lazy placeholder for all the unexplored territory of consciousness-altering drugs. He’s convinced we can get much tighter. That’s why his team at Mindstate Design Labs is using AI to engineer precision-designed states of consciousness.

We asked Dillan how his religious upbringing (and speaking in tongues) shaped his vision, how Mindstate is carrying forward the Shulgin legacy, and what he's learned about the link between drug chemistry and entity encounters.

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How did your early experiences with altered states of consciousness shape what you're building with Mindstate Design Labs?

My experiences with altered states started much younger than typical. I grew up in a new religious movement centered on the group practice of an altered state—an endogenously produced hyper-arousal, dissociative trance state based on the speaking in tongues of the Pentecostal tradition. It was central to my life from childhood.

Coming out of that environment, I was trying to find that direct engagement with the divine, the transcendent, the profound. I'd heard about psychedelics throughout my life, with public figures talking about their potential to elicit transformative encounters. When I finally tried psychedelics in my twenties, it was completely transformative on a personal level. Various mental health diagnoses I had pretty much immediately went away after those experiences.

Like most people in the psychedelic space, there was that personal direct experience where the light switch goes on and you see how transformative it can be. With my professional background in biotech venture capital and operations, it seemed obvious that a rigorous scientific approach to understanding these states—at the molecular, neural, and subjective levels—was what was needed. Bringing specific states of consciousness to patients with mental health disorders seemed like the highest impact and most immediate thing we could do to bring good to the world.

Mindstate seems to be carrying forward the Shulgin legacy in many ways. What aspects of their approach are you most committed to preserving, and where are you taking things in new directions?

Yes, our scientific founder is Dr. Tom Ray, who was a longtime collaborator with the Shulgins, and Ann Shulgin was actually the third owner in the company after the two founders.

There's this quote from Sasha that we keep repeating: "My motivation isn't necessarily to make medicines. My motivation isn't to trip on drugs. My motivation is that of a tool maker.” He viewed his work as a stepping stone to understanding how chemicals and the brain relate to the mind. That's really the through line of what we're trying to accomplish.

Our interest in psychedelics isn't so much taking psilocybin or MDMA and developing those as therapies, though I'm glad people are doing that. What I think is a much bigger deal is using these tools to safely and carefully perturb specific combinations of neurotransmitter activity and relate that biochemistry to what happens in the mind.

When you understand those relationships, you can turn psychedelics into something else. You can extract individual sub-segments of the psychedelic experience. When you can isolate the awe of psilocybin, or take just the clarity or empathy or aesthetic enhancement, those compounds aren't psychedelics anymore.

The thing we're continuing from the Shulgins is the relation of chemical structure to phenomenology. They made drugs, ate them, and reported on their experiences. We've made that process much more scaled, systematic, and quantitative by using giant databases of trip reports and using semantic embedding spaces of LLMs to quantify phenomenology via language. We're building on the shoulders of giants here, trying to scale and quantify what they started.

What made you choose 5-MeO-MiPT as your foundation compound? Why does it work so well for designing specific states?

One general pattern we've observed is that as the breadth of pharmacological interaction increases, the range of phenomenology also increases. When you have a psychedelic that's less pharmacologically promiscuous—acting on fewer receptors—like 5-MeO-MiPT, the experience tends to have less variance and be less interesting from a recreational perspective.

On the other end of the spectrum, DMT hits a very large number of sites across the central nervous system, resulting in a much more complex experience. Trip reports often include entirely novel environments and interactions with entities. Sasha used the term "psychedelic tofu" to describe compounds that are relatively bland, boring, with a narrow phenomenological profile. We did a wide-scale initial assay of psychedelics against different brain sites, and found about five that had that characteristic.

We chose 5-MeO-MiPT partly because it pretty much only hit serotonin and had a narrow range of experience. The tofu term described how it didn't have distinct phenomenological features of its own, so it could be put on top of other psychedelics to amplify whatever their flavor is. It gave us the opportunity to test the thesis that you can take a serotonergic pharmacology and bring in other pharmacology to modulate the nature of the experience in certain ways.

Also, as you increase the dose, the visual effects increase at a much slower rate than the emotional and cognitive effects. Being able to deliver cognitive and emotional flexibility without a push toward hallucinations offers an advantage as we test our pharmacological and phenomenological theses.

The FDA approval process is organized around treating specific conditions, not designing states of consciousness. How do you navigate that gap when developing your compounds?

I'd clarify that we're absolutely interested in and focused on creating medicines for patients. What's more interesting though is that there's something beyond just taking existing compounds and pushing them through the FDA process. Using psychedelics as tools to understand the mind builds a much bigger tech tree.

If we're sending a patient in to do a dose of psilocybin, we're basically saying, "Hey, here are the contents of your subconscious. Good luck." If we can turn that into a paradigm where we're addressing your specific condition and the underlying factors that contributed to your diagnosis, that's powerful. Psychiatric diagnoses have no biological basis; they're clusters of symptoms existing for insurance and diagnostic purposes.

We already have fairly good evidence that specific states of consciousness drive specific outcomes for specific patient populations. Once you understand how to hit the right biology to get the right effect on consciousness, the next step is understanding how those effects on consciousness help patients with specific diseases.

We'll certainly be treating people with depression, anxiety, and other conditions applicable to psychedelics. I'd also love to treat disorders currently thought of as outside the scope of psychedelics, or even medicine. If you develop this ability to precision design mood, cognition, and perception, there are all kinds of applications beyond immediate medical applications—extending to digital substrates, brain-computer interfaces, and virtual reality.

What's the most surprising connection you've discovered between a drug's chemistry and the subjective experience it creates?

Our Osmanthus platform uses AI models, statistical models, and manual processes to analyze thousands of trip reports alongside pharmacological data. That's where all the IP is, so it's tough to answer completely. But there's one pattern I’ll share that might interest people.

We’ve identified a particular receptor subtype in the human brain that highly correlates with entity experiences. There's a specific biochemistry that DMT has prominently—DMT being famous for entities—while psilocybin has a much lower relative affinity at this particular receptor subtype. This corresponds with the observation that as psilocybin doses get higher, reports of entity contacts increase.

Maybe it's as simple as that—an "entity receptor." You hit the serotonin pharmacology that you need to hit and then you hit this other pharmacology, and voilà, you get entities. Or you could do the reverse and design a DMT without entities.

This research has me thinking about the whole concept of what we even mean by "psychedelics." I've never been able to get a satisfactory answer as to what fundamentally separates LSD from the drugs in your medicine cabinet. You take 700mg of Benadryl or 500mg of Robitussin and you’ll have a psychedelic experience. I'm interested in moving past that word and paradigm.

The therapeutics that have really worked for mental health disorders are acutely psychoactive. We’ve discovered how to bottle the emotion of confidence with amphetamines, or contentment with benzodiazepines, but there are only a handful of those. There are so many other human emotional or cognitive states that can be extraordinarily therapeutically valuable. "Psychedelics" is just a lazy umbrella term for all the classes of psychoactive therapeutics that haven't been discovered yet, which is probably almost all of them.

Want more from Dillan?

Read about Mindstate Design Labs' neuroengineering platform and drug development pipeline, or apply for a job on their team.

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DISCLAIMER: This newsletter is for educational and informational purposes only and is not intended as a substitute for professional medical advice. The use, possession, and distribution of psychedelic drugs are illegal in most countries and may result in criminal prosecution.