Beyond new treatments, the company also hopes its approach will shed light on consciousness itself.<\/p>\n\n\n\n
\u201cIf we could figure out which differences in psychedelic pharmacology drive which differences in consciousness, we\u2019d understand the mechanisms of consciousness in an entirely new way,\u201d Mindstate CEO Dillan DiNardo wrote<\/a> in 2024. \u201cAnd we could begin using those mechanisms to design an innumerable variety of psychoactive effects \u2014 intentionally and with precision.\u201d<\/p>\n\n\n\n At the heart of Mindstate\u2019s platform is Osmanthus, a large language model trained to predict how psychedelic experiences unfold, drawing on thousands of trip reports and scientific texts. The company recently cleared a major hurdle: FDA approval to launch a Phase 1 clinical trial, which will take place in the Netherlands. The trial centers on \u201cmoxy\u201d (5-MeO-MiPT), a compound the team hopes to use as the foundation for a new category of precision-designed psychedelics.<\/p>\n\n\n\n The main idea is to strategically combine moxy \u2014 a relatively mild and predictable psychedelic \u2014 with other drugs, psychedelic or not, to produce specific effects in mood, cognition, and perception<\/a>. As DiNardo put it<\/a>, moxy might prove to be a “blank canvas on which to paint infinite possibilities.”<\/p>\n\n\n\n DiNardo started his career in finance before moving into biotech, working at a billion-dollar life sciences fund and holding operational roles in several early-stage drug development startups. But his interest in altered states runs deeper. He grew up in Pennsylvania in what he calls a \u201cnew religious movement centered on the group practice of altered states of consciousness,\u201d where members frequently entered hyper-arousal, dissociative trance states. \u201cThat area of altered states of consciousness was very central to my life, from the time I was a pretty small child,\u201d he told Big Think.<\/p>\n\n\n\n In his twenties, DiNardo was diagnosed with PTSD and depressive disorder, turning to psychedelic therapy for relief.<\/p>\n\n\n\n \u201cThere were various ways in which psychedelic therapy was being done legally in different jurisdictions, and so I always came to it from, you know, not the not the Burning Man angle, but more of the therapeutic or ceremonial angle.\u201d<\/p>\n\n\n\n While he\u2019s quick to note that \u201cwe need Phase 3 trials for proof that psychedelics work in this way,\u201d DiNardo experienced their transformative power firsthand, noting that he hasn\u2019t qualified on any rating scales for his previous disorders in years. But what truly gripped him wasn\u2019t just the therapeutic benefit \u2014 it was the variation. \u201cWhy do different psychedelics do different things? Can we look at the biological basis of the difference in psychedelic effects in order to better navigate these types of states of consciousness, to be able to design specific states of consciousness?\u201d<\/p>\n\n\n\n This question led him to connect with Mindstate\u2019s scientific founder, Tom Ray, an evolutionary biologist who believed altered states arise when psychedelics activate receptors in the brain on specific \u201cmental organs,\u201d corresponding to functions like joy, consciousness, and reason. Together, they selected the compound moxy as a starting point for designing tailored psychedelic experiences.<\/p>\n\n\n\n Though you may never have heard of it, moxy is far from new. It was synthesized in 1985 in a lab in Lafayette, California, by medical chemists Alexander \u201cSasha\u201d Shulgin and David B. Repke. Shulgin synthesized most of the world\u2019s psychedelic drugs and tested many of them on himself and his wife Ann, documenting their effects in books like “TiHKAL” (“Tryptamines I Have Known and Loved”) and “PiHKAL” (“Phenethylamines I Have Known and Loved”). <\/p>\n\n\n\n Moxy stood out because it combined some effects of classical psychedelics like LSD and psilocybin with the entactogenic (or \u201cempathy-promoting\u201d) properties of MDMA: \u201ca decreased sense of self-criticism, an increased ability to think about things that you normally avoid thinking about, and an additional sense of sympathetic warmth.\u201d<\/p>\n\n\n\n Ray, who had collaborated with the Shulgins, helped identify the most qualitatively distinct compounds the couple had developed. DiNardo says:<\/p>\n\n\n\n \u201cTom had those [analyzed] against all of these sites across the human brain to be able to understand a bit better: How do these drugs interact differently with the brain, and how do those differences in biology correlate to the differences in consciousness?\u201d \u201cWhat we found over the years is that there are a handful of psychedelic drugs Sasha Shulgin called ‘psychedelic tofu,’ which have a narrow pharmacological and phenomenological profile,\u201d DiNardo says, explaining that the range of effects and receptors targeted is much narrower compared to most other psychedelics (only targeting the 5HT2A receptor). <\/p>\n\n\n\n In other words, moxy\u2019s mild effects might make it easy to build on \u2014 absorbing the character of other compounds without overpowering them.<\/p>\n\n\n\n \u201cThey don’t have as much flavor on their own. At standard clinical doses, moxy is not going to give you the ego loss of 25 milligrams of psilocybin. It’s not going to give you the entity interactions of DMT or some of these wilder and crazier effects of psychedelics.\u201d <\/p>\n\n\n\n In underground settings, however, moxy is often used as a \u201cbase ingredient\u201d that, when combined with other drugs, can alter the altered state, so to speak, modulating the subjective effects of those drugs. <\/p>\n\n\n\n \u201cThat’s similar to what we’re doing,\u201d DiNardo says. \u201cWe’re taking this tofu \u2014 because it gives us a lot more modular control over the pharmacology \u2014 and determining […] the effect on consciousness that these molecules are going to have. We\u2019re developing moxy not just by itself but as the base component for a series of combination drugs that are intended to induce different effects on consciousness.\u201d <\/p>\n\n\n\n How does Mindstate come up with the recipe for those combinations?<\/p>\n\n\n\n Extending the Shulgins\u2019 tradition of documenting altered states, Mindstate is applying machine learning to organize and analyze psychedelic experiences at a scale never before attempted. Using their LLM, Osmanthus, they can process hundreds of thousands of drug reports from internet sites like Reddit, books like the Shulgins’, and scientific papers to create a kind of psychedelic fortune-telling machine, which can connect biology, pharmacology, and phenomenology to minimize the guesswork in how a trip will unfold. <\/p>\n\n\n\n Osmanthus\u2019s diet includes two types of data sets: pharmacological and subjective. The platform\u2019s core innovation is connecting those two layers \u2014 linking how a drug behaves in the body with how people describe its effects. Osmanthus maps subjective experiences using \u201csemantic embedding models\u201d (machine learning tools that extract meaning from language) trained on language from trip reports, while its pharmacological data includes thousands of receptor binding assays. Together, these datasets have allowed Mindstate to build what the company describes<\/a> as a catalog of over 600 distinct psychedelic effects, each tied to the brain sites likely responsible. <\/p>\n\n\n\n The goal isn\u2019t just to predict how a given trip will unfold but to build a programmable framework for engineering entirely new experiences.<\/p>\n\n\n\n Their theory, based on the data so far, is that you tend to see increasingly unique effects as psychedelics interact with more receptors. For example, DMT, which has one of the broadest effects across various receptors, often causes powerful and bizarre psychedelic experiences, such as entity encounters. Drawing off the LLM\u2019s predictions, Mindstate may someday be able to control those effects, using moxy as a buffer to safely engineer customized psychedelic states. <\/p>\n\n\n\n “If you can\u2019t label something and talk about it, you can\u2019t measure it.”<\/p>Dillan DiNardo<\/cite><\/blockquote><\/figure>\n\n\n\n For now, their foray into machine learning has provided surprising insights, some of which may be useful to psychedelic scientists. By analyzing the commonly reported \u201cmystical experience\u201d at a more nuanced level, for example, their model found that people often report experiencing ego death (loss of a sense of separation from environment) but not<\/em> loss of contact with their environment. This observation isn\u2019t captured by the Mystical Experience Questionnaire researchers typically use, DiNardo says. <\/p>\n\n\n\n Other observations may be less useful. \u201cEnvironmental Cubism,\u201d for instance, is a rare effect marked by Picasso-like visuals (they haven\u2019t nailed the drugs or receptors linked to that effect, he jokes, as it\u2019s not particularly therapeutically relevant).<\/p>\n\n\n\n Eventually, Osmanthus may be able to tell them, at the most fine-grained level, what the structure of \u201call human experience\u201d is when taking psychedelics. From there, he says, \u201cyou can map out the entire tree from the single node of any subjective effect to the categories to the individual words and phrases people use.\u201d <\/p>\n\n\n\n To that end, one of Mindstate\u2019s core aims has been to crack the code of the ineffable. \u201cIf you can\u2019t label something and talk about it, you can\u2019t measure it.\u201d <\/p>\n\n\n\n It\u2019s no easy feat \u2014 translating everyday, nonpsychedelic experiences into words is hard enough. As the Irish playwright George Bernard Shaw famously quipped, \u201cThe single biggest problem in communication is the illusion that it has taken place.\u201d <\/p>\n\n\n\n One concern surrounding models such as ChatGPT has been \u201challucinations\u201d and other inaccurate interpretations of text, leading to misleading claims about the world. Considering psychedelic experiences are already trippy enough, Mindstate must ensure nothing gets lost in translation. A key question: Are trip reports enough to establish what psychedelic researchers call \u201cecological validity,\u201d meaning accurate representation of how various drugs are experienced in various settings? What\u2019s more, will these predictions carry over to a clinical setting, where mental health treatment is perhaps most relevant? Can an LLM pull data from Reddit to accurately inform the highly controlled environment of a clinical trial?<\/p>\n\n\n\n Mindstate isn\u2019t claiming to be able to calculate the exact incidence of an effect, DiNardo says. <\/p>\n\n\n\n \u201cThese are raw, unstructured reports. They’re in specific settings. People tend to report some things over other things. What these reports give us is a very close characterization of which pharmacologies contribute to which experiences across all settings, and then that points us to what to replicate in the clinic. Ultimately, the final answer always comes down to, when you are in the clinical setting where these drugs are going to be administered, how do the set and the setting and the pharmacology interact?\u201d<\/p>\n\n\n\n “You absolutely cannot just dump trip reports in a machine learning pipeline and expect it to work.”<\/p>\nDillan DiNardo<\/cite><\/blockquote>\n\n\n\n When it comes to translating experience at scale, there are pros and cons to using LLMs.<\/p>\n\n\n\n \u201cThe large language models are definitely not perfect,\u201d DiNardo says. \u201cThere have been huge improvements, even just over the past year, certainly. I would say, though, that it is essential to have a human in the loop.\u201d <\/p>\n\n\n\n One way to go about this is to start off with the model, run it across a bunch of trip reports, and then have human domain experts take a look. These are people who have undergone many psychedelic trips; understand psychonaut subculture; know the language and references, including common metaphors people use to describe their experiences; and can categorize what those people are talking about. <\/p>\n\n\n\n \u201cWe fork the processes such that we’re using a human-created ontology of subjective effects that is very detailed \u2014 and, we think, the best in the world \u2014 and we’re using that human ontology and human feedback to train the model,\u201d DiNardo says. \u201cThen we have other models where it\u2019s just the large language model, or whatever machine learning method there is, and it comes up with its own ontology and is a bit more objective.\u201d<\/p>\n\n\n\n Both of those approaches have their advantages and disadvantages, he says. The human might be more accurate while the LLM might be more complete. <\/p>\n\n\n\n \u201cYou absolutely cannot just dump trip reports in a machine learning pipeline and expect it to work. It takes a lot of human expertise in combination with AI.\u201d<\/p>\n\n\n\n DiNardo thinks we\u2019ll likely come to understand human consciousness in tandem with a deeper understanding of artificial intelligence. Mindstate hopes to be the one to \u201cbreak the clock apart and see the mechanisms within\u201d in a targeted and safe way. Down the road, there could even be potential to combine psychedelics with brain-computer interfaces (BCIs)<\/a>. For the time being, the target is mental health, and models like Osmanthus could help nudge psychedelics into the realm of precision medicine. <\/p>\n\n\n\n However, researchers still don\u2019t know how psychedelics \u2014 or any altered state of consciousness (ASC), for that matter \u2014 help improve the symptoms of various disorders. So it would be fair to raise concerns that \u201cdesigner ASCs\u201d may be putting the cart before the horse. <\/p>\n\n\n\n “There is a much wider world of psychedelic effects beyond the ones that we already know about.”<\/p>Dillan DiNardo<\/cite><\/blockquote><\/figure>\n\n\n\n When pressed to comment on mental health research, DiNardo points to the complexity of factors involved and how little a diagnosis tells us about the root causes of a disorder. Psychedelics are similar in that way, he says.<\/p>\n\n\n\n \u201cMost people would agree psychedelics have a multi-scale mechanism of action: pharmacological, cellular, neuroplasticity, brain networks, psychological. The question of \u2018How do you extract one piece of that out?\u2019 is not necessarily a question that\u2019s interesting to me.\u201d <\/p>\n\n\n\n What\u2019s much more interesting to him, he says, is the mapping between those things, adding that, when it comes to mental health treatment, \u201csometimes you may only be able to intervene at one level of that multiscale mechanism,\u201d whether it\u2019s with SSRIs or psychotherapy. <\/p>\n\n\n\n Mindstate\u2019s Phase 1 clinical trial aims to test the safety and efficacy of moxy on humans. The trial isn’t yet testing Mindstate\u2019s full vision. It\u2019s an early-stage study designed to evaluate moxy\u2019s safety, how it behaves in the body, and how participants respond. But DiNardo already has his eye on the part where their research team is \u201cdecorating the psychedelic tofu\u201d with various combinations of drugs to test how Osmanthus\u2019s predictions hold up in a controlled clinical setting. <\/p>\n\n\n\n \u201cAt that point, we will have validated that we can design states of consciousness and that there is a much wider world of psychedelic effects beyond the ones that we already know about,\u201d he muses. \u201cThat’s coming immediately afterward. We hope to start those studies very shortly.\u201d <\/p>\n\n\n\n This article was reprinted with permission of Big Think<\/a>, where it was originally published<\/a><\/em>.<\/p>\n","protected":false},"excerpt":{"rendered":" A look inside Mindstate Design Labs’ effort to design drugs that reliably produce specific states of consciousness.<\/p>\n","protected":false},"author":25,"featured_media":115840,"template":"","ftm_taxonomy_fields":[46,78,119],"ftm_taxonomy_challenges":[],"ftm_taxonomy_statuses":[],"ftm_taxonomy_hidden_tags":[],"class_list":["post-115839","ftm_article","type-ftm_article","status-publish","has-post-thumbnail","hentry","ftm_taxonomy_fields-ai","ftm_taxonomy_fields-drugs","ftm_taxonomy_fields-psychology"],"acf":[],"apple_news_notices":[],"yoast_head":"\n![\"A](\"https:\/\/www.freethink.com\/wp-content\/uploads\/2025\/04\/mindstate-.jpg?quality=75&w=1000\")
Different drugs, different trips <\/h3>\n\n\n\n
Carrying on the Shulgin torch<\/h3>\n\n\n\n
(Ann Shulgin was a co-owner of Mindstate Design Labs until her death in 2022.)<\/p>\n\n\n\n![\"Older](\"https:\/\/www.freethink.com\/wp-content\/uploads\/2025\/04\/Sasha-and-Ann.jpg?quality=75&w=960\")
Training AI on human experience<\/h3>\n\n\n\n
The limits of language<\/h3>\n\n\n\n
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Mental health: More than the sum of its parts<\/h3>\n\n\n\n