Designing States of Consciousness: Unique Approaches to Psychedelic Drug Development

Podcast Highlights

• Dillan’s journey from fundamentalist religious upbringing to finding psychedelics
• Sasha and Ann Shulgin, Tom Ray, and the origin story of Mindstate Design Labs
• Joining startup accelerator Y Combinator
• Intentionally designing states of consciousness
• The role of language and AI in altered states of consciousness
• Suing the DEA and winning

Show Links

1. Mindstate Design Labs
2. Dillan on Twitter
3. (podcast) Hamilton Morris - Beyond the Mainstream: Insights from Psychedelic Chemistry, Culture, & Consciousness

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Podcast Transcript

0:00:00.0 Paul F. Austin: Hey, listeners, welcome back to the Psychedelic Podcast by Third Wave, where we explore how psychedelics can be integrated into culture for the evolution of humanity. This is your host, Paul F. Austin, and today I'm speaking with Dillan DiNardo, CEO of Mindstate Design Labs.

0:00:18.0 Dillan DiNardo: We believe there are so many states of consciousness that existing psychedelics do not yet provide access to. What happens when we start combining drugs that hit serotonin 2A with other targets that no psychedelic has ever hit before? And what we're seeing in unstructured and informal human data outside of the clinic is that there are these new states of consciousness. So what's most interesting from a long-term perspective is completely novel states of consciousness that you don't get with psilocybin, you don't get with LSD, you don't get with kind of first generation legacy psychedelics. If we can move into that space, it expands the whole psychedelic world in an exponential way. And we do think that the psychedelics that exist are really just the tip of the iceberg.

0:01:03.2 Paul F. Austin: Welcome to the Psychedelic Podcast by Third Wave audio Mycelium, connecting you to the luminaries and thought leaders of the psychedelic renaissance. We bring you illuminating conversations with scientists, therapists, entrepreneurs, coaches, doctors, and shamanic practitioners, exploring how we can best use psychedelic medicine to accelerate personal healing, peak performance, and collective transformation.

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0:02:37.2 Paul F. Austin: Hey listeners, this is Paul F. Austin, founder and CEO at Third Wave, and today we bring you a fascinating conversation on discovering new states of consciousness for the advancement of mental health. My guest is Dillan DiNardo, who is the CEO of Mindstate Design Labs. Dillan is one of the few Y Combinator backed companies within the psychedelic sector Mindstate Design Labs is a next-generation psychedelic biotech company, designing novel altered states of consciousness for mental health therapeutics. The company's mission is to map the biological basis of the varieties of psychedelic experience, enabling the precision design of novel altered states in a deeper understanding of the biological basis of consciousness. Mindstate Design Labs backers include Y Combinator and founders of OpenAI, Neuralink, AngelList, Coinbase, Instacart, and Twitch. Prior to Mindstate Design Labs, Dillan worked in a $1 billion venture fund executing and managing biopharma medical devices and health tech investments ranging from pre-seed to publicly traded companies.

0:03:41.7 Paul F. Austin: In our conversation together, Dillan starts off by sharing his experience growing up in a fundamentalist Pentecostal religious community and how he came to psychedelics for healing and spiritual discovery. We then dive into the origin story of Mindstate Design Labs involving the late Sasha and Ann Shulgin. We also explore the role of AI and large language models and in understanding how developing language further can help us to design more specific altered states of consciousness. And Dillan also talks about his experience suing the DEA and winning advocating for the research of specific psychoactive compounds. My biggest takeaway from this conversation was this relationship between language and science, how the English language in and of itself is not very expansive and adaptable specific to altered states of consciousness. And part of what Dillan is doing with Mindstate Design Labs is collecting qualitative research, subjective experiences to help inform the refinement of certain psychoactive compounds.

0:04:48.4 Paul F. Austin: So he's really taking the methodology, the original methodology of Sasha Shulgin who used to try these drugs that he would invent by himself, and then with a small group of friends and saying, how can we leverage technology to scale that approach? And so that way we're not as reliant on surveys numbers, but actually more interested in the qualitative aspects of how people communicate about their subjective experience. So, really fascinating conversation. And as always, you can go deeper into this episode by following the link in the description. You'll find full show notes, transcripts, and any links that we mention today. All right, that's it for now. I hope you enjoy my conversation today with Dillan DiNardo.

0:05:36.6 Paul F. Austin: Hey, listeners, welcome back to the psychedelic podcast. Today we have Dillan DiNardo, the CEO of Mindstate Design Labs. Dillan, welcome to the show.

0:05:42.9 Dillan DiNardo: Thanks, Paul, for having me.

0:05:44.6 Paul F. Austin: Where are you calling in from today?

0:05:45.6 Dillan DiNardo: I'm in Pittsburgh, Pennsylvania, Steel City.

0:05:50.0 Paul F. Austin: What's it like there? The weather? I mean, we're recording this end of January. Is it freezing cold or is it warmed up again?

0:05:56.0 Dillan DiNardo: Yeah, no, it's actually pretty beautiful outside. It's temperamental, the weather over here. It's famous for changing from absolute freezing to warm day after day.

0:06:09.4 Paul F. Austin: Okay. All right. Are you from Pittsburgh originally?

0:06:09.9 Dillan DiNardo: So I was born in North Carolina, moved up to, Pittsburgh when I was, very young about two, and I have been here, ever since. Went to school, up here and, started working for the internal venture arm of the big healthcare system and insurance company in Pennsylvania. And, then founded in Mindstate Design Labs and have just been in Pittsburgh ever since.

0:06:34.0 Paul F. Austin: Fantastic. All right. So we have a lot. I think what's interesting about Mindstate Design is the vision, the fact that you have been backed by Y Combinator, the fact that Ann Shulgin was one of the three original owners in Mindstate Design, how you sued the DEA and won, right? You got a lot to go off of here. This is gonna be a pretty fascinating conversation just so everyone is aware. But Dillan, where I want to start is your story. So, you grew up in a new religious movement centered on the group practice of an endogenously generated trance state. Tell us more about that.

0:07:16.1 Dillan DiNardo: Yeah, that's, ultimately what brought me to psychedelics. I was, as you said, kind of, raised in this, tight-knit and a little bit, isolated religious community that was really focused on this particular practice. So this was, sort of on the edges of fundamentalist Pentecostalism but there there's this state of trans commonly associated with speaking in tongues, right? So people think about speaking in tongues as people just, kind of making up sounds and trying to get into it. But really the vocalization aspect is this higher level structure built on the substructure of a trance state. So in the academic literature around it's referred to as a hyper arousal dissociative trance state. So it's kind of tripping.

0:08:11.3 Dillan DiNardo: It's an altered state of consciousness, but it's endogenously produced. There are no drugs involved. And, I'm sure, Paul, you're well familiar with, many different ways of inducing altered states of consciousness, the meditation and, float tanks and the list goes on and on. But this was, this kind of state of consciousness was a thing that had a corporate manifestation, right? So it was done in a group. And speaking in tongues was a practice that was pretty common in, say the 1800s, the 1900s in these, religious revivals, primarily in the United States. But something started happening at some point during those revivals where someone would just kind of enter that trance state and breakout into, into speaking in tongues. And they would start singing it, right?

0:09:05.9 Dillan DiNardo: So it was this vocalization, but there was a melody and the people around them would start joining in. And so what happened was that there was no planning, but as groups of people would kind of enter into this state, there was this vocalization aspect. Everyone was singing with different notes. There was no planning, there was no agreement about what key to start in, but the whole thing just kind of melds together in this really beautiful sound. And so there's this manifestation, this audio element of the corporate trance state, and it, it kind of has a life of its own, and it, it rises and falls and rises and falls. This sound it's kind of like, an Aeolian harp, right? If you've familiar with that instrument, like just the winds playing all these notes together and it creates kind of the, one way of expressing it is the sound of mini waters, right?

0:10:00.0 Dillan DiNardo: So, the practice of this particular trance state was really central to the community, central to the religious belief system. And so from the time I was a very small child alter states of consciousness were really central to my life. So when I left that community I guess the you'd taken the Pentecostal out of the church, but the church was still kind of in the Pentecostal, right? So I still had this desire for, I guess this connection to, direct encounter with the profound or the transcendent, this altered state of consciousness. And so that's what interested me in psychedelics. And as I listened to, various public figures talking about how psychedelics gave, very, very easy and direct access to these kinds of states that's what kind of set me along the psychedelic path. And so that's my story and, where I came from.

0:11:00.6 Paul F. Austin: Why'd you leave? What inspired you to leave the church, the faith? Bring us a little bit deeper into that decision making process for you?

0:11:08.8 Dillan DiNardo: Yeah. Many reasons. I think, a lot of it was the, the fundamentalist belief structure, right. So everything that comes along with with fundamentalist, religion the ways in which I guess science is not taken as seriously. The ways in which the belief structure is elevated above compassion for people. Right, so homophobia and looking at people on the outside as really the other, rather than being motivated from a place of compassion. And so it had ended up, being a situation where it was a very isolated group. And as time went on it just became more and more, untenable. And so I did come out of that experience with various, kind of mental health diagnoses. And so when I went into psychedelics, it was not so much from a therapeutic place, it was more of a spiritual search or a psychological search.

0:12:18.4 Dillan DiNardo: But I quickly found that, after those just early psychedelic experiences, my diagnoses of PTSD and major depressive disorder and ADHD all just went away. I just didn't qualify on the scales for any of that anymore. And so there was this, kind of, I had this direct experience and of how psychedelics can produce these changes in people, and maybe more importantly, I had these direct experiences of how different psychedelics did very different things. So that the way that MDMA can produce changes in you is very different from the way that psilocybin or 5-MeO-DMT or different psychedelics can drive healing outcomes or different perspectives on yourself. And so that was part of what brought me to Mindstate Design Labs this observation that psychedelics are not this monolithic entity, but rather that different molecules have have different kind of silos of experience, even though you can experience very different things under psilocybin from one experience to the other there, there are borders, right? And those borders don't totally overlap with each other. There are parts of DMT that are distinct from psilocybin and so on. And so that's part of what led to Mindstate Design Labs as I got connected to our scientific co-founder, Tom Ray who is looking at these qualitative differences and thinking about psychedelics not just as an end to themselves, but as tools for studying the architecture of the mind, the way that the mind and consciousness emerges from the brain.

0:13:52.9 Paul F. Austin: The story healing from this religious cultish trauma. I grew up quite religious, not so fundamentalist Protestant Reformed, RCA Reformed Church of America. I've talked about it at length in the podcast, so I won't discuss it too much. But what I've noticed is there are a lot of people who are leaving the Mormon church or have left the Mormon church, Jehovah's Witnesses, then I know of other Fundamentalist Christians who have found tremendous healing and perspective through psychedelics, because like you, I was much more of a scientific rational person. And so when I left the church, I became an atheist more or less. And then it was only through my own personal psychedelic experiences that I sort of rediscovered, oh, there's some truth here. It just was sort of conflated or corrupted by the sort of dogmatic structure of how we navigate it.

0:14:42.1 Paul F. Austin: So I think that hearing that story is powerful, and I think what it's led you to is super interesting. I mean, when we first connected probably a year or so ago, now, maybe a year and a half ago, I was just sort of fascinated by the overall approach. And what it reminded me of was this quote by Eldous Huxley, which is more or less that we've finished exploring the continent or the physical land masses of the earth, right? Colonization and exploration. We've gone past that phase, and the next phase is really exploring what he called the inner antipodes of our mind. And so when we work with psychedelics, as you mentioned, we open that aperture of consciousness, but we open the aperture of consciousness in very distinct ways, depending on the type of psychedelic that's used.

0:15:31.6 Paul F. Austin: And of course, the most common ones that we know about are, I would say lysergamides, tryptamines, and phenethylamines. And there are a lot of nuances and differences between each one of those and between the different compounds, as you mentioned, even DMT and Psilocybin they're both tryptamine, but obviously the differences in the states that they facilitate are significant and substantial. So I really wanna, like, I wanna spend a lot of our podcasts focusing on that. And before we get into that, tell us a little bit about the origin story that, of Mindstate Design Labs. How is it that Ann Shulgin was one of the original three owners and tell us a little bit more about Tom Ray and the work that he has done with self-evolving, artificial life and you know, other contributions that he's made to science.

0:16:24.2 Dillan DiNardo: Sure, yeah. This discussion of the distinctions among psychedelics and what it means for consciousness is just my favorite conversation topics. I'm looking forward to talking about that. But yeah, the Mindstate Design lab story really starts with the Shulgins as many psychedelic stories do. So most of your listeners are probably familiar with the Shulgins, but Sasha and Ann Shulgin are commonly called the godparents of psychedelics. And they're responsible for I would say, most psychedelics that exist in the world today. So in the '80s and '90s in particular Sasha Shulgin had this DEA license and, just created various psychedelics hundreds of psychedelics and ate them himself and reported on the experiences. And then as he came across the more interesting compounds, he would share them with his wife Ann, and a group of, friends and colleagues. And that's why most psychedelics exist because the Shulgins, created the drugs and then published the syntheses published the phenomenological content of the experiences in their books, PiHKAL an TiHKAL. And so the...

0:17:35.4 Paul F. Austin: Which stands for just so folk, it stands for Tryptamines, I have come to know and love.

0:17:45.3 Dillan DiNardo: Yeah. Tryptamines, I have Known and Loved, and Phenethylamine I Have Known and Loved. Yeah, exactly. So that's why there even is this qualitative diversity among psychedelics. Back in the, I don't know, in maybe the '50s and '60s, there were the classical psychedelics. There was mescaline, LSD, psilocybin, DMT. And people do talk about the differences among some of these drugs, but really the focus was very much on LSD and psilocybin, which are some of the most similar psychedelics. So the fact that the Shulgins, even created these drugs and released them out into the world is the only reason we can really observe these phenomenological distinctions, these ways in which different psychedelics produce different changes to consciousness. And so our scientific founder, Dr. Tom Ray, was a friend and collaborator of the Shulgins.

0:18:41.6 Dillan DiNardo: Tom is a fascinating character. He is one of these Polymaths who's made seminal contributions to just multiple fields of science. And so he actually started out, doing natural history in the jungle. And as an undergrad, he was already publishing in the Journal of Science. Science is one of the top scientific journals. It's, it's kind of the, the pinnacle of a career, the achievements of making a contribution to science that makes it into one of these top journals. And he's already doing it as an undergrad. So he started college at the age of 16 started kind of making these discoveries out in the jungle just coming into nature and looking at nature, not with preconceived hypotheses, not necessarily using that scientific method of testing hypotheses, but just looking with open eyes at what patterns might exist and finding fundamental new patterns.

0:19:41.0 Dillan DiNardo: And so from his career in the jungle, he then went into the field of artificial life. So Tom had no background in computer science whatsoever. But in order to accomplish what he did in artificial life, he created an entirely new operating system, a new CPU architecture, a new machine code. And in so doing, he was able to accomplish what no one in the field of artificial life could do, which was the first instance of artificial life to evolve by natural selection. And that was the first instance of, I guess, life overall, after life on Earth, to evolve by natural selection. And so you can look that up. The program was called Tierra. But it was kind of this same approach of natural history and considering patterns from first principles that characterized Tom's method. And so after his artificial life accomplishments, he moved into psychedelics. So this observation that different psychedelics produce very different effects was something he had back in the '70s. I think he was 16 years old, trying some different psychedelics and observing those differences. But he'd waited all those years to really be able to execute on that insight. And so in the 2000s, he and Sasha selected a variety of these psychedelic drugs, most of which were created by Sasha, and had them assayed. So these were the broadest assays of psychedelic drugs. And what I mean by assays is the way in which we look at how psychedelics interact with various receptors in the brain.

0:21:26.8 Dillan DiNardo: So as a broad statement, psychedelics are very promiscuous, pharmacologically speaking. They interact with a lot of different sites across the brain. The 5-HT2A, the serotonin 2A subtype, is commonly regarded as one of the, or the central psychedelic target. But psychedelics are doing all of these different things across the brain. And so there's this central insight that if the pharmacology varies, and if the psychedelics produce very different types of experience, that has to come from somewhere. And a likely candidate for the source of the qualitative diversity of psychedelics is the activity of these psychedelics across different sites in the brain. And so Tom was kind of carrying on in Sasha's tradition. But what he had that Sasha didn't was these wide-scale assays, this snapshot of how psychedelics are interacting at the pharmacological level. And so that technology and that approach forms the foundation of Mindstate Design Labs, forms the foundation of our data science and our approach to connecting distinct aspects of psychedelic phenomenology. So alterations of sense of self or sense of time, or mood, or cognition, or emotion to the underlying pharmacology. And looking at those pieces so that we can sort of do recombinant psychedelics, so that we can dissect these different pieces and then use that understanding to intentionally design states of consciousness.

0:23:00.5 Dillan DiNardo: So I connected with Tom at some point. So I don't know, possibly 2020. And we just found this commonality of vision, this kind of obsession with understanding the qualitative diversity and the biological basis of the varieties of psychedelic experience. And so that's where Mindstate Design Labs came from.

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0:24:44.7 Paul F. Austin: And what did you do professionally before becoming CEO of Mindstate Design Labs?

0:24:50.2 Dillan DiNardo: I was in biotech venture capital. So I started my career in finance, doing a lot of mergers and acquisitions, and that buying and selling companies is a piece of the skill set of VC. And so I moved into venture capital, worked in biotech, did a lot of investments across different companies at various stages of the life sciences life cycle. So very early stage companies, very late stage, phase three, publicly traded kinds of companies and everything in between. I invested across a pretty wide variety of disease indications and modalities. So there were small molecules and gene therapies and cell therapies and med devices. And in addition to that investing capacity, I would also work in operational roles. So when we have a piece of technology that was really just nothing but a scientific breakthrough that was ready to be commercialized, I would step in and help to stand up the company and hire the management team and get things off the ground.

0:25:54.5 Paul F. Austin: So interesting. Okay, so you meet Tom in 2020, you step in as CEO of Mindstate Design Labs, right? You're getting it up and off the ground and then you join Y Combinator. And Y Combinator is more or less the gold standard of incubators based in SF and the tech scene, started by Paul Graham and run by Sam Altman for many years before Sam became the CEO of OpenAI. Tell us why you chose to join Y Combinator, what that process was like and how it's impacted the success and trajectory of Mindstate Design Labs.

0:26:33.6 Dillan DiNardo: Yeah, YC is amazing. And there are many reasons we chose to kind of be a YC portfolio company. I think one of the big one, one of the big reasons was the network that it provided. So there is this close alliance, I think, between Silicon Valley culture and psychedelics. Famously, Steve Jobs credits a lot of his ways of thinking and his accomplishments to his LSD experiences. And the kind of the, I don't know, the birthplace of the '60s was right around Berkeley, San Francisco, the Bay Area. So there's this deep history and this deep interconnectedness between Silicon Valley and the tech world and psychedelics. And so the vision that we had was a vision of using psychedelics to make these technological breakthroughs. And so that was something we knew would be close to the hearts of kind of the Silicon Valley crowd. So being able to kind of insert ourselves into the heart of Silicon Valley at Y Combinator was just a very obvious choice for us in particular.

0:27:51.0 Dillan DiNardo: And that's in addition to the many advantages that Y Combinator provides. Being able to be around amazing people. There's that saying, right, that you are the average of the five people you spend the most time with. And in Y Combinator, you're surrounded by all of these people who are very ambitious, who are trying to solve difficult problems for people, who are building things, who have a vision to really change the world in a positive way. And so being in that kind of environment is just a huge advantage in that. That was another big reason. So many other reasons, but YC was really incredible both for getting access to that network. It's also, YC is very good at training you how to build a kind of a generational company, kind of a company that makes a dent in the universe. So I had already had that background in venture capital, but the ethos of Y Combinator, the way in which they simplify things, the way in which they train you to think about what is the heart of the matter, what is the first domino that knocks down all the other dominoes, and the way they teach you to communicate, like you're talking to a five-year-old. All of the advice from Y Combinator, it's not these complicated strategies to execute on things. It's all about simplicity and focus, and that's why they become so effective, and that's why all of these multi-billion dollar companies are coming out of Y Combinator.

0:29:36.6 Dillan DiNardo: Airbnb and Coinbase and Twitch and Instacart and many of these kinds of companies. So yeah, that's how we got connected to the whole Silicon Valley ecosystem, and I think we did succeed in bringing in some support and some resources for the psychedelic world from Silicon Valley. So our seed round was led by Initialized Capital, which was founded by Gary Tan, who's now the president over at Y Combinator. A number of other VCs, and we also had investments from Angels, including the founders of OpenAI and Neuralink, AngelList, Coinbase, Instacart, Twitch, many of these kinds of companies. And so that was great for us. I think it was great for the psychedelic movement, for psychedelic science in general. But our vision of using psychedelics, not just as ends in themselves, but as tools to probe the infrastructure of the minds and create new states of consciousness, that really resonated and it was just a great fit for us.

0:30:41.4 Paul F. Austin: All right, so I have a question, which is sort of building on a lot of what we've been talking about so far. And a lot of what I've spoken about in the podcast before is like new paradigms, new systems, and I think we would both agree that the weaving in of psychedelics into both our mental healthcare system, but also in leadership, places of influence and power could really start to shift the way that we look at healthcare, education, technology, business, et cetera, et cetera. So as both of us are very well aware of, and I would say almost all of the listeners are well aware of, AI is having a moment. And there's a lot of talk about AI, including large language models.

0:31:24.4 Paul F. Austin: So I'd be curious to hear your thoughts on the following. How is psychedelic work through, let's say, Mindstate Design Labs, how is that differentiated from just a classic pharmaceutical company that's working on novel drugs for, let's say, psychiatry? So how does Mindstate Design differ from that? And what might be the role of AI and large language models to help, let's say, companies like Mindstate Design weave in the necessary context for understanding altered states of consciousness, the impact of altered states of consciousness, the impact of drugs on different types of altered states of consciousness? I'd just love to hear you talk a little bit at length about pharmaceutical versus Mindstate Design, and then how AI can amplify these sort of models of drug development that you're focused on.

0:32:25.4 Dillan DiNardo: Yeah, so our technology and our platform is fundamentally based on human experience, right? So you can't design a state of consciousness, you can't produce a state of consciousness unless someone first experiences it and talks about it. And so that's fundamentally where the technology comes from. One of the challenges then of drawing the connection between a subjective experience of an ultra-conscious state to the underlying biology is that subjective experience is very difficult to quantify. So if Sasha Shulgin took a drug, say he took 2C-B, and he said, well, this was wonderful, it was a little bit intactogenic and pro-social, and it was a fairly easy headspace, and the colors were nice, and the sensory amplification was nice, but it wasn't immediately bringing me to the heart of my childhood trauma. So he can talk about what the drug produced for him, but how do you then quantify that? How do you then relate it to the biology, especially because these drugs do produce such different effects across different people, and even within one individual who's taking a given drug at different periods in time, the experience is going to be different. So one of the fortuitous kind of aspects of history here is that as we were founding Mindstate Design Labs, natural language processing and large language models in particular were really taking off.

0:34:05.1 Dillan DiNardo: So because the Shulgins released all of these hundreds of drugs into the world, they really developed a subculture within the psychedelic subculture of psychonauts who like to experiment with the more exotic varieties of these compounds and who record their experiences in detail. So Paul, you're familiar with sites like Erowid, people report on their experiences and discuss them in detail on Reddit and various drug forums online and on the dark webs even. So what has ultimately resulted from that is that we've been able to collect 70,000 trip reports of people who've taken these psychedelic drugs. So you have all of this information, there's this huge database with which you can compare different people across a given psychedelic, by which you can compare different psychedelics to each other and by which you can even disentangle the pharmacology of psychedelics. So to kind of oversimplify an example here, if you look at psychedelics that hits a certain subtype of dopamine receptor and then you look at psychedelics that do not hit that particular subtype of dopamine receptor and you just then cross compare the experiential aspects of all of the reports from each of those drugs, you can look at the gap. You can see, okay, which phenomenological features, which types of subjective experience appeared in those drugs that hit that dopamine subtype versus the drugs that did not.

0:35:37.2 Dillan DiNardo: And so what emerges from that is a correlation between a specific type of altered state of consciousness and this underlying biological target that you can target with a new psychedelic drug or a combination of drugs. And so language is really an amazing thing. It's the medium of data that has the most richness. It has more data per bit than any other medium of information about human subjective experience. And language is really this mirror of cognition. In a sense, the world is made of language and we are made of language. And now that we have these really advanced natural language processing techniques and these large language models, we can see the structure of human perception within the structure of language. And we can quantify it. And we can see how far apart different experiences are from each other. And we can measure that in a very quantitative way. So with large language models and with the semantic space that they provide, we can really quantitatively demonstrate the distinction between different psychedelics and the distinction between the underlying pharmacology, the underlying receptors that these different psychedelics have.

0:36:54.1 Dillan DiNardo: And so it's that use of large language models to synthesize broad amounts of pharmacological data with broad amounts of human experience data that we can then combine with really the more firsthand direct human experience of these drugs to sort out what is the biological basis of conscious experience.

0:37:15.6 Paul F. Austin: So a question that I have then that I'm curious about as we build on this is what is the business model? In other words, what are all these investors that you brought in? I mean, I could guess, like I have some sense of you're maybe bringing certain substances into like an IND process. And then the ones that show certain types of promise, you may sell to other biotech companies is to bring them through full phase one, phase two, phase three clinical trials. That's my first guess. Another guess would be that you want to choose or select sort of the ideal or best molecules that you land on. And then you yourself as a company will bring those through phase three clinical trials, ideally to medicalization. But there's gotta be a lot more nuance in that. And so I'd love to hear you talk just a little bit at length about how is this actually a business and not just sort of like a fun hobby, figuring out how drugs impact us in different unique and novel ways.

0:38:18.0 Dillan DiNardo: Yes, yes, I think figuring out how drugs impact us in different ways are really the key, the central thing to creating the entire next generation of psychedelic therapeutics. And so you are absolutely correct on both counts, we have this platform that is producing all of the these different drugs and drug combinations, by the way, we're very much looking at combinations, which I can go into, but the point here is, is yes, to develop the drugs ourselves we have now filed our IND for our lead program, so we're moving into human studies with our first drug very soon, but the platform is producing far more drugs for more precision design states of consciousness and we can develop ourselves, and so the model is very much to work with other companies to co-develop, to license, to partner, to give this portfolio of Different states of consciousness to the world and to get it out there as quickly and safely as possible.

0:39:23.3 Dillan DiNardo: But fundamentally, if you. First, let me talk about the premise here about the mechanisms of psychedelic action, so there is this debate generally within psychedelic science about what causes the HEAL. What causes the therapeutic impact, is it this neuroplasticity effect that comes from 5-HT2A or is it the experience itself, and we very much firmly land on the idea that it is the experience itself, it is the interaction of the higher order brain structures with the environments, that creates therapeutic impact, so that acute altered state of consciousness that gives you a fundamentally new perspective, or that lets you enter into a space that gives you a fundamentally new insight into your identity or your environment or your history that drives these therapeutic processes.

0:40:19.6 Dillan DiNardo: And so, if that is your premise, if you do agree that it is the altered state of consciousness that drives the therapeutic outcomes, the central problem in psychedelic science from a development perspective becomes there is no translational model for altered states of consciousness. There's no animal, there's no mouse that you can inject with a drug, and then mice can tell you. Oh, I had this type of ego officer, I saw these entities, or I had these various types of experiences there was just no translational ability. And having a translational model is fundamental to drug development to screen molecules and decide what to spend the millions of dollars on. You have to have some insight, and so that's fundamentally the problem that we're solving, any other approach of just doing MED-Cam on existing psychedelics and trying to make new psychedelic molecules, in that approach, you can kind of take out the low-hanging fruit, you can try to optimize certain parameters, you can try to reduce the duration of action of the molecule, but you can't design a state of consciousness, you can't say, Oh hey, it's the ego loss, where it's the sense of sacredness or any of these different types of altered state of consciousness.

0:41:35.5 Dillan DiNardo: You can't connect that thing that drives the treatment outcomes to the underlying biology, and so there's no way to drive a drug development process, and that's the problem that we've solved here with our platform, this predictive model where we're fundamentally basing it on human experience, but we also bring in this quantitative element of connecting the pharmacology and connecting the pharmacology up to the brain region, and then the phenomenology of the altered state, having that full connection and that ability to intentionally design a state of consciousness with a particular drug and drug combo. That's really the central advantage so to take just one specific example here, so the state of consciousness that I think that's been the most well studied in terms of its therapeutic impact is the altered state of consciousness of oceanic boundlessness, the ego loss the mystical experience, cluster of factors. So there are a number of sub-factors here the ineffability of the sense of sacredness transcending some time space, the ego dissolution, a number of other things, but in various trials, researchers have drawn these very direct links between those experiences and the outcomes very, very broadly speaking, there's this type correlation between, does the patient actually have that mystical experience, if they do, they're probably going to get better, whether you're looking at substance use disorder, depression and anxiety, what have you.

0:43:05.3 Dillan DiNardo: It's so tightly connected, people can get the same dose of the drug, but if they don't have the specific state of consciousness, if they don't have that experience, then you're not gonna see the therapeutic outcome. So one way to optimize drug here is to develop drugs that reliably and safely induce specifically those elements of the mystical experience that seem to drive the therapeutic outcomes according to the study so far. So that's one example. There are other states of consciousness, they're tightly linked to therapeutic outcomes, but I think what might be even more interesting from just from a human perspective as well as a commercial perspective, is that we believe there are so many states of consciousness that existing psychedelics do not yet provide access to. So there's this this kind of unspoken assumption in all of the psychedelics world that the realm of possible psychedelic experience is defined by, say, seven or so molecules, the classical psychedelics, 5-MeO-DMT, Ibogaine Salvia maybe, Ketamine. So it's almost as if the entire box with which we're looking at altered state of consciousness is those drugs, but what happens when we start combining drugs that hit serotonin 2A with other targets that no psychedelic has ever hit before, other receptors in the brain that no other psychedelics hit.

0:44:32.2 Dillan DiNardo: And what happens there, and what we're seeing in unstructured and informal human data outside of the clinic is that there are these new states of consciousness, so what's most interesting from a long-term perspective is completely novel state of consciousness that you don't get with psilocybin, you don't get with LSD, you don't get with goodies, first generation legacy psychedelics. And so if we can move into that space, it expands the whole psychedelic world in an exponential way, and we do think that the psychedelics, they exist are really just a tip of the iceberg, so that's ultimately the commercial application and different mental health disorders that also beyond FDA kind of applications.

0:45:15.6 Paul F. Austin: What you're talking about, I think, is relevant and important, which is these translational models that utilize language to better refine or clarify the subjective experiences that people are having, so there's more nuance around how we might reach these various altered states of consciousness depending on our intention for the day for the week, for the month, for the year for our lifetime, and so I think there's a beautiful sort of artistry with mind state design that essentially it would be amazing to get to a point where it's like. And I remember when I lived in New York many years ago, I met with this guy who was trying to do this for Keurigs, essentially create psychedelic pods that you could put in a Keurig like coffee machine and boom, you'd get a...

0:46:07.8 Paul F. Austin: A psychedelic coffee that would have the specific thing, this is Dr. Z, who I'm sure you're somewhat familiar with who's invented all of these sort of novel psychedelics, and the topic then many years ago, just like the topic now has been, English is very limited in terms of our capacity to communicate about altered states of consciousness, so this is... I think largely a cultural limitation, whereas if you look at the Shipibo are a great example in Shipibo and the language in and of itself, there's a much richer language that's about connection to the Earth, connection to the environment, connection to the land, connection to the trees, into the Amazon, because that is the context in which they've grown as a people, whereas in English, altered states of consciousness have been taboo for so long because of how intermingled English has been with sort of puritanical culture as it sort of us back even to the story that we both let off it so I think this concept of how do we expand even the English language in and of itself through these altered states of consciousness, how does...

0:47:27.4 Paul F. Austin: 'cause English is also one of the most flexible languages that we have available, it's very malleable, it's very adaptable, and so I almost see what you're doing as supporting the evolution of how we communicate and speak through the lens of altered states of consciousness, which if you look at it from a large mission vision perspective, 30, 50, 70, 100 years from now, that is a very sort of compelling and curious and interesting way to go. Okay, yeah, on the ground practically, right now, we're drug development, we're looking at different altered states of consciousness, we're utilizing AI to create a novel translational method that allows us to better navigate these altered states, but if it's like the real macro is like, How are you actually changing the English language in and of itself, to make it more acceptable to alter our state of consciousness for very unique outcomes.

0:48:29.1 Dillan DiNardo: Yeah, that's very insightful. We can't evolve any more quickly, than our language does, we can't go anywhere unless our language goes there first, and in Mindstate Design Labs, we have put quite a great deal of effort into articulating the ineffable, into expanding the realm of what can be said. And so what's really key to some of these quantitative systems to connect subjective states of experience to underlying biology is the language itself, if you can't articulate it, then you can't measure it. So as an example, there's this measurement instruments, the most, I'd say, commonly used measurement instrument in psychedelic trials, which is the 11D-ASC as the altered states of consciousness scale, and so this is what's used to kind of get our heads around what kind of experiences people are having in the 11D-ASC to take for, an example, visual elements, and so the visual aspect of consciousness, there's types of effects, the 11D-ASC splits visuals into two categories. In our system, we have, I think, something like 56 categories of visual effects, and we have definitions for those effects and for almost all of them I think we have replication, so actual artistic replications of exactly what those visuals look like.

0:49:53.1 Dillan DiNardo: So I use the visuals as an example, the visual effects are not necessarily the most therapeutically relevant aspect of altered state of consciousness, but we've done the same thing to these cognitive effects and the mood effects, and all of these things that psychedelics do, the weird ways that they change perception, and so developing that language and developing the system, the hierarchy of categories here was a crucial and unavoidable step to being able to do what we're doing, so. Yeah, I think that's very insightful. Language is really at the center of all this, somehow at the center of consciousness, at the center of reality, and these breakthroughs and large language models, I think are giving us a new picture into what that looks like.

0:50:44.3 Paul F. Austin: And I think it goes back to even the question that I had around pharmaceutical versus Mindstate Design, and sort of old paradigms versus new paradigms that are amplified by AI and artificial intelligence, and how might our utility of these large language models help us to adapt and evolve our language structure at a quicker rate to encompass these alternates of consciousness that could ultimately have a very positive and beneficial outcome on the world around us and how we relate to it, and so there's almost like this point of conversion that's convergence, that's developing that Mindstate Design is playing a substantial role in which is AI language alter states of consciousness that are oriented towards a more regenerative systemic perspective of how we look at education, healthcare technology, business. I think it's a very sort of. And it's no coincidence that I think it's coming out of Silicon Valley in many ways because of how informed Silicon Valley has been by psychedelics for so long.

0:51:46.6 Dillan DiNardo: And Terence McKenna said that the drugs of the future will look like computers and the computers in the future will look like drugs, there's this sense in which these things are kind of intersecting, this gets a little bit into the Roma science fiction a bit far into the future here, but that is the direction we're going, and ultimately, as we learn to understand how does our subjective conscious experience connect to the underlying biology, and as we use language as the central linchpin to connect those pieces, I think we'll get closer and closer to the point where we deeply understand how consciousness works, we deeply understand the biological basis of consciousness, and then we have the keys and the triggers to induce very specifically, very intentionally the states of consciousness that are helpful, and that is indescribable powerful thing and a dangerous thing eventually, so I think it's a very good thing that this is all. Much of this is happening under the FDA, highly regulated contexts, but ultimately, I think this is where. All the contradictions kind of resolve, everything kind of compresses together, the language and the drugs and the consciousness.

0:53:07.4 Paul F. Austin: Okay, so final quick, so we're on the Verein up, but I wanna hear about how you sued the DEA and won. Let's go into that.

0:53:16.4 Dillan DiNardo: That was back in, I believe, February of 2020. This was the five tryptamines matter. So many listeners will probably be familiar with what happened there, the DEA posted a notice on the federal register that's they were planning to schedule five new psychedelics, and so these psychedelics are qualified under the analog Act, so the analog Act basically says. As it related to drugs if it looks like a duck and quacks like a duck then it's a duck, so if it kind of does things like psychedelics, it's a psychedelic. It's illegal, you can still buy and sell it, you can order these kinds of drugs online, you can ship them anywhere, you can do research with them, but once there becomes an intention to consume, then it's treated just like a schedule one drug, and that's...

0:54:09.6 Dillan DiNardo: I think it's effective for certain purposes, so it allows these obscure drugs that aren't public health hazards to be researched with much less red tape, once you get into a schedule one drug, the costs just explode, and as a biotech company, all early stage biotechs are basically all of the state biotechs are very decentralized. You're relying on a lot of different contract research organizations, and so if you move from the land of schedule one analog to actual schedule one drugs, all of a sudden, the amount of partners, the amount of contract research organizations who are able to handle that, a heavy regulatory burden really decrease in it stifles innovation, so just a very bad idea on many fronts, because of what we're doing with looking at all of these different psychedelics, looking at the qualitative diversity investigating biology, you have a great variety of psychedelic drugs.

0:55:14.1 Dillan DiNardo: Several of the drugs listed in that Federal Register notice, we were interested in one of the drugs we were actively manufacturing, and so we were put in this position where we had standing to challenge the action. So when the DEA post something that they really have the ability to just do what they want, unless there is some institution or individual who has standing to challenge the process, and so the heroes of the story or really Matt Zorn at Yetter Coleman and Graham who you know over Calyx Law and Graham Pechenik and they tried to bring together a coalition of companies, and what ended up happening was we at Mindstate Design Labs teamed up with Tactogen, there were a few other, Hamilton Morris and his group kind of joined on with their own separate action and some others.

0:56:22.5 Dillan DiNardo: And there was a very, I think IT'S just a wonderful public outcry from researchers, from public at large kind of contesting this action, but we along with Tactogen and others were in kind of that. I don't know if it's a fortunate or unfortunate spot, I see it as a fortunate though, to be able to have standing to actually request a DEA hearing. And so, long story short, I think just the lawyers were really good lawyers, and it ultimately got to the point where the hearing was coming up, I was scheduling my plane tickets and hotels for Washington DC to go and testify the hearings, and we got the emails from the DEA saying that they were just kicking the drugs back to the Department of Health and Human Services, so it was kind of a face-saving move for the DEA, so the scheduling process involves both the DEA and the Department of Health and Human Services.

0:57:26.9 Dillan DiNardo: The Department of Health and Human Services has to first do an evaluation of the drugs and the DEA has to been acted based on the evaluation of those drugs. And one of the many arguments that we were bringing up is that the report from HHS that the DEA was relying on was woefully antiquated, it was from years and years ago. Really before, I would say in modern psychedelic science, and so now it's being kept back to HHS. We haven't heard anything since then. And so I don't know if it will come up again, but I really don't think that the right answer to regulation of psychedelics as more and more psychedelic proliferate, adding those psychedelics to schedule one just does so much to stifle innovation and the drugs are already regulated, they're already illegal for human consumption. And so it was. It took some time and effort, but I was glad to be in that position where we could kind of turn the tide of it, and that was the first time in history I think that the DEA has backed down from the scheduling a psychedelic drug.

0:58:39.7 Paul F. Austin: Congrats. That's fantastic. Well, Dillan, this has been a fascinating conversation. I'm glad, I know we've talked about these topics privately on a handful of occasions, but to be able to have this conversation publicly to share more about your vision of Mindstate Design, and if folks wanna learn more about Mindstate Design it's mind-state.design. And it's a beautiful website or page, you can learn more about what Dillan and Tom Ray and their whole team, they're up to. Any other assets or resources or things that you wanna sort of point listeners to check out after this conversation, Dillan.

0:59:19.3 Dillan DiNardo: You can hit me up on Twitter at Dillan DiNardo. D-I-L-L-A-N D-I-N-A-R-D-O look at our websites feel free to get in touch. But Paul, I really appreciate talking to you. It was a great conversation. And thanks for having me on.

0:59:40.5 Paul F. Austin: Hey listeners, Paul here. I hope you enjoyed our episode today with Dillan DiNardo, if you're loving the psychedelic podcast, make sure you follow the show wherever you're listening and share your insights and experiences by leaving a review, your thoughts could be the key to someone else's transformative journey. Thanks for tuning in and for joining us and amplifying Psychedelic Awareness. Until next time.