Ways of Thinking

Related to: On the Medium of Thought, John von Neumann, Early Isolation Tank Psychonautics: 1970s Trip Reports, Pseudo-Time Arrow, Thinking in Numbers, High-Entropy Alloys of Experience, A Single 3N-Dimensional Universe: Splitting vs. Decoherence, A New Way to Visualize General Relativity, Visual Quantum Physics, and Feynman’s QED Video Lectures (highly recommended!)


Transcript from the last section of the 1983 BBC interview of Richard Feynman “Fun to Imagine” (excerpt starts at 55:52):

Interviewer presumably asks: What is it like to think about your work?

Well, when I’m actually doing my own things, that I’m working in the high, deep, and esoteric stuff that I worry about, I don’t think I can describe very well what it is like… First of all it is like asking a centipede which leg comes after which. It happens quickly and I am not exactly sure… flashes and stuff goes on in the head. But I know it is a crazy mixture of partial differential equations, partial solving of the equations, then having some sort of picture of what’s happening that the equations are saying is happening, but they are not as well separated as the words that I’m using. And it’s a kind of a nutty thing. It’s very hard to describe and I don’t know that it does any good to describe. And something that struck me, that is very curious: I suspect that what goes on in every man’s head might be very, very different. The actual imagery or semi-imagery which comes is different. And that when we are talking to each other at these high and complicated levels, and we think we are speaking very well and we are communicating… but what we’re really doing is having some kind of big translation scheme going on for translating what this fellow says into our images. Which are very different.

I found that out because at the very lowest level, I won’t go into the details, but I got interested… well, I was doing some experiments. And I was trying to figure out something about our time sense. And so what I would do is, I would count trying to count to a minute. Actually, say I’d count to 48 and it would be one minute. So I’d calibrate myself and I would count a minute by counting to 48 (so it was not seconds what I counted, but close enough), and then it turns out if you repeat that you can do very accurately when you get to 48 or 47 or 49, not far off you are very close to a minute. And I would try to find out what affected that time sense, and whether I could do anything at the same time as I was counting and I found that I could do many things, but couldn’t do other things. I could… For example I had great difficulty doing this: I was in university and I had to get my laundry ready. And I was putting the socks out and I had to make a list of how many socks, something like six or eight pair of socks, and I couldn’t count them. Because the “counting machine” was being used and I couldn’t count them. Until I found out I could put them in a pattern and recognize the number. And so I learned a way after practicing by which I could go down on lines of type and newspapers and see them in groups. Three – three – three – one, that’s a group of ten, three – three – three – one… and so on without saying the numbers, just seeing the groupings and I could therefore count the lines of type (I practiced). In the newspaper, the same time I was counting internally the seconds, so I could do this fantastic trick of saying: “48! That’s one minute, and there are 67 lines of type”, you see? It was quite wonderful. And I discovered many things I could read while I was… I could read while I was counting and get an idea of what it was about. But I couldn’t speak, say anything. Because of course, when I was counting I sort of spoke to myself inside. I would say one, two, three… sort of in the head! Well, I went down to get breakfast and there was John Tuckey, a mathematician down at Princeton at the same time, and we had many discussions, and I was telling him about these experiments and what I could do. And he says “that’s absurd!”. He says: “I don’t see why you would have any difficulty talking whatsoever, and I can’t possibly believe that you could read.” So I couldn’t believe all this. But we calibrated him, and it was 52 for him to get to 60 seconds or whatever, I don’t remember the numbers now. And then he’d say, “alright, what do you want me to say? Marry Had a Little Lamb… I can speak about anything. Blah, blah, blah, blah… 52!” It’s a minute, he was right. And I couldn’t possibly do that, and he wanted me to read because he couldn’t believe it. And then we compared notes and it turned out that when he thought of counting, what he did inside his head is that when he counted he saw a tape with numbers, that did clink, clink, clink [shows with his hand the turning and passing of a counting tape], and the tape would change with the numbers printed on it, which he could see. Well, since it’s sort of an optical system that he is using, and not voice, he could speak as much as he wanted. But if he wanted to read then he couldn’t look at his clock. Whereas for me it was the other way.

And that’s where I discovered, at least in this very simple operation of counting, the great difference in what goes on in the head when people think they are doing the same thing! And so it struck me therefore, if that’s already true at the most elementary level, that when we learn about mathematics, and the Bessel functions, and the exponentials, and the electric fields, and all these things… that the imagery and method by which we are storing it all and the way we are thinking about it… could be it really if we get into each other’s heads, entirely different? And in fact why somebody has sometimes a great deal of difficulty understanding when you are pointing to something which you see as obvious, and vice versa, it may be because it’s a little hard to translate what you just said into his particular framework and so on. Now I’m talking like a psychologist and you know I know nothing about this.

Suppose that little things behaved very differently than anything that was big. Anything that you are familiar with… because you see, as the animal evolves, and so on, as the brain evolves, it gets used to handling, and the brain is designed, for ordinary circumstances. But if the gut particles in the deep inner workings whereby some other rules and some other character they behave differently, they were very different than anything on a large scale, then there would be some kind of difficulty, you know, understanding and imagining reality. And that is the difficulty we are in. The behavior of things on a small scale is so fantastic, it is so wonderfully different, so marvelously different than anything that behaves on a large scale… say, “electrons act like waves”, no they don’t exactly. “They act like particles”, no they don’t exactly. “They act like a kind of a fog around the nucleus”, no they don’t exactly. And if you would like to get a clear sharp picture of an animal, so that you could tell exactly how it is going to behave correctly, to have a good image, in other words, a really good image of reality I don’t know how to do it!

Because that image has to be mathematical. We have mathematical expressions, strange as mathematics is I don’t understand how it is, but we can write mathematical expressions and calculate what the thing is going to do without actually being able to picture it. It would be something like a computer that you put certain numbers in and you have the formula for what time the car will arrive at different destinations, and the thing does the arithmetic to figure out what time the car arrives at the different destinations but cannot picture the car. It’s just doing the arithmetic! So we know how to do the arithmetic but we cannot picture the car. No, it’s not a hundred percent because for certain approximate situations a certain kind of approximate picture works. That it’s simply a fog around the nucleus that when you squeeze it, it repels you is very good for understanding the stiffness of material. That it’s a wave which does this and that is very good for some other phenomena. So when you are working with certain particular aspect of the behavior of atoms, for instance when I was talking about temperature and so forth, that they are just little balls is good enough and it gives us a very nice picture of temperature. But if you ask more specific questions and you get down to questions like how is it that when you cool helium down, even to absolute zero where there is not supposed to be any motion, it’s a perfect fluid that hasn’t any viscosity, has no resistance, flows perfectly, and isn’t freezing?

Well if you want to get a picture of atoms that has all of that in it, I can’t do it, you see? But I can explain why the helium behaves as it does by taking my equations and showing that the consequences of them is that the helium will behave as it is observed to behave, so we now have the theory right, but we haven’t got the pictures that will go with the theory. And is that because we are limited and haven’t caught on to the right pictures? Or is that because there aren’t any right pictures for people who have to make pictures out of things that are familiar to them? Let’s suppose it’s the last one. That there’s no right pictures in terms of things that are familiar to them. Is it possible then, to develop a familiarity with those things that are not familiar on hand by study? By learning about the properties of atoms and quantum mechanics, and practicing with the equations, until it becomes a kind of second nature, just as it is second nature to know that if two balls came towards each other they’d mash into bits, you don’t say the two balls when they come toward each other turn blue. You know what they do! So the question is whether you can get to know what things do better than we do today. You know as the generations develop, will they invent ways of teaching, so that the new people will learn tricky ways of looking at things and be so well trained that they won’t have our troubles with picturing the atom? There is still a school of thought that cannot believe that the atomic behavior is so different than large-scale behavior. I think that’s a deep prejudice, it’s a prejudice from being so used to large-scale behavior. And they are always seeking to find, to waiting for the day that we discover that underneath the quantum mechanics, there’s some mundane ordinary balls hitting, or particles moving, and so on. I think they’re going to be defeated. I think nature’s imagination is so much greater than man’s, she’s never gonna let us relax.


From the blog Visual Quantum Physics (same as gifs above):

7 Recent Videos: Rational Analysis of 5-MeO-DMT, Utility Monsters, Neroli, Phenomenal Time, Benzo Withdrawal, Scale-Specific Network Geometry, and Why DMT Feels So Real

5-MeO-DMT: A Rational Analysis at Last (link)

Topics covered: Non-Duality, Symmetry, Valence, Neural Annealing, and Topological Segmentation.

See also:


Befriending Utility Monsters: Being the Adult in the Room When Talking About the Hedonic Extremes (link)

In this episode I connect a broad variety of topics with the following common thread: “What does it mean to be the adult in the room when dealing with extremely valenced states of consciousness?” Essentially, a talk on Utility Monsters.

Concretely, what does it mean to be responsible and sensible when confronted with the fact that pain and pleasure follow a long tail distribution? When discussing ultra-painful or ultra-blissful experiences one needs to take off the glasses we use to reason about “room temperature consciousness” and put on glasses that actually take these states with the seriousness they deserve.

Topics discussed include: The partial 5HT3 antagonism of ginger juice, kidney stones from vitamin C supplementation, 2C-E nausea, phenibut withdrawal, akathisia as a remarkably common side effect of psychiatric medication (neuroleptics, benzos, and SSRIs), negative 5-MeO-DMT trips, the book “LSD and the Mind of the Universe”, turbulence and laminar flow in the “energy body”, being a “mom” at a festival, and more.

Further readings on these topics:


Mapping State-Spaces of Consciousness: The Neroli Neighborhood (link)

What would it be like to have a scent-based medium of thought, with grammar, generative syntax, clauses, subordinate clauses, field geometry, and intentionality? How do we go about exploring the full state-space of scents (or any other qualia variety)?

Topics Covered in this Video: The State-space of Consciousness, Mapping State-Spaces, David Pearce at Oxford, Qualia Enrichment Kits, Character Impact vs. Flavors, Linalool Variants, Clusters of Neroli Scents, Neroli in Perfumes, Neroli vs. Orange Blossom vs. Petigrain vs. Orange/Mandarin/Lemon/Lime, High-Entropy Alloys of Scent, Musks as Reverb and Brown Noise, “Neroli Reconstructions” (synthetic), Semi-synthetic Mixtures, Winner-Takes-All Dynamics in Qualia Spaces, Multi-Phasic Scents, and Non-Euclidean State-Spaces.

Neroli Reconstruction Example:

4 – Linalool
3 – Linalyl Acetate
3 – Valencene
3 – Beta Pinene
2 – Nerolione
2 – Nerolidol
2 – Geraniol Coeur
2 – Hedione
2 – Farnesene
1 – D-Limonene
1 – Nerol
1 – Ambercore
1 – Linalool Oxyde
70 – Ethanol

Further readings:


What is Time? Explaining Time-Loops, Moments of Eternity, Time Branching, Time Reversal, and More… (link)

What is (phenomenal) time?

The feeling of time passing is not the same as physical time.

Albert Einstein discovered that “Newtonian time” was a special case of physical time, since gravity, relativity, and the constancy of the speed of light entails that space, time, mass, and gravity are intimately connected. He, in a sense, discovered a generalization of our common-sense notion of physical time; a generalization which accounts for the effects of moving and accelerating frames of reference on the relative passage of time between observers. Physical time, it turns out, could manifest in many more (exotic) ways than was previously thought.

Likewise, we find that our everyday phenomenal time (i.e. the feeling of time passing) is a special case of a far more general set of possible time-like qualities of experience. In particular, in this video I discuss “exotic phenomenal time” experiences, which include oddities such as time-loops, moments of eternity, time branching, and time reversal. I then go on to explain these exotic phenomenal time experiences with a model we call the “pseudo-time arrow”, which involves implicit causality in the network of sensations we experience on each “moment of experience”. Thus we realize that phenomenal time is an incredibly general property! It turns out that we haven’t even scratched the surface of what’s possible here… it’s about time we do so.

Further readings on this topic:


Benzos: Why the Withdrawal is Worse than the High is Good (+ Flumazenil/NAD+ Anti-Tolerance Action) (link)

Most people have low-resolution models of how drug tolerance works. Folk theories that “what goes up must come down” and theories in the medical establishment about how you can “stabilize a patient on a dose” and expect optimal effects long term get in the way of actually looking at how tolerance works.

In this video I explain why benzo withdrawal is far worse than the high they give you is good.

Core arguments presented:

  1. Benzos can treat anxiety, insomnia, palpitations, seizures, hallucinations, etc. If you use them to treat one of these symptoms, the rebound will nonetheless involve all of them.
  2. Kindling – How long-term use leads to neural annealing of the “withdrawal neural patterns”.
  3. Amnesia effects prevent you from remembering the good parts/only remembering the bad parts.
  4. Neurotoxicity from long-term benzo use makes it harder for your brain to heal.
  5. Arousal as a multiplier of consciousness: on benzos the “high” is low arousal and the withdrawal is high arousal (compared to stimulants where you at least will “sleep through the withdrawal”).
  6. Tolerance still builds up even when you don’t have a “psychoactive dose” in your body – meaning that the extremely long half-life of clonazepam and diazepam and their metabolites (50h+) entails that you still develop long-term tolerance even with weekly or biweekly use!

I then go into how the (empirically false) common-sense view of drug tolerance is delaying promising research avenues, such as “anti-tolerance drugs” (see links below). In particular, NAD+ IV and Flumazenil seem to have large effect sizes for treating benzo withdrawals. I AM NOT CONFIDENT THAT THEY WORK, but I think it is silly to not look into them with our best science at this point. Clinical trials for NAD+ IV therapy for drug withdrawal are underway, and the research to date on flumazenil seems extremely promising. Please let me know if you have any experience using either of these two tools and whether you had success with them or not.

Note: These treatments may also generalize to other GABAergic drugs like gabapentin, alcohol, and phenibut (which also have horrible withdrawals, but are far shorter than benzo withdrawal).

Further readings:

Epileptic patients who have become tolerant to the anti-seizure effects of the benzodiazepine clonazepam became seizure-free for several days after treatment with 1.5 mg of flumazenil.[14] Similarly, patients who were dependent on high doses of benzodiazepines […] were able to be stabilised on a low dose of clonazepam after 7–8 days of treatment with flumazenil.[15]”

Flumazenil has been tested against placebo in benzo-dependent subjects. Results showed that typical benzodiazepine withdrawal effects were reversed with few to no symptoms.[16] Flumazenil was also shown to produce significantly fewer withdrawal symptoms than saline in a randomized, placebo-controlled study with benzodiazepine-dependent subjects. Additionally, relapse rates were much lower during subsequent follow-up.[17]

Source: Flumazenil: Treatment for benzodiazepine dependence & tolerance

Scale-Specific Network Geometry (link)

Is it possible for the “natural growth” of a pandemic to be slower than exponential no matter where it starts? What are ways in which we can leverage the graphical properties of the “contact network” of humanity in order to control contagious diseases? In this video I offer a novel way of analyzing and designing networks that may allow us to easily prevent the exponential growth of future pandemics.

Topics covered: The difference between the aesthetic of pure math vs. applied statistics when it comes to making sense of graphs. Applications of graph analysis. Identifying people with a high centrality in social networks. Klout scores. Graphlets. Kinds of graphs: geometric, small world, scale-free, empirical (galactic core + “whiskers”). Pandemics being difficult to control due to exponential growth. Using a sort of “pandemic Klout score” to prioritize who to quarantine, who to vaccinate first. The network properties that made the plague spread so slowly in the Middle Ages. Toroidal planets as having linear pandemic growth after a certain threshold number of infections. Non-integer graph dimensionality. Dimensional chokes. And… kitchen sponges.

Readings either referenced in the video or useful to learn more about this topic:

Leskovec’s paper (the last link above):

Main Empirical Findings: Our results suggest a rather detailed and somewhat counterintuitive picture of the community structure in large networks. Several qualitative properties of community structure are nearly universal:

• Up to a size scale, which empirically is roughly 100 nodes, there not only exist well-separated communities, but also the slope of the network community profile plot is generally sloping downward. (See Fig. 1(a).) This latter point suggests, and empirically we often observe, that smaller communities can be combined into meaningful larger communities.

• At size scale of 100 nodes, we often observe the global minimum of the network community profile plot. (Although these are the “best” communities in the entire graph, they are usually connected to the remainder of the network by just a single edge.)

• Above the size scale of roughly 100 nodes, the network community profile plot gradually increases, and thus there is a nearly inverse relationship between community size and community quality. This upward slope suggests, and empirically we often observe, that as a function of increasing size, the best possible communities as they grow become more and more “blended into” the remainder of the network.

We have also examined in detail the structure of our social and information networks. We have observed that an ‘jellyfish’ or ‘octopus’ model [33, 7] provides a rough first approximation to structure of many of the networks we have examined.

Ps. Forgot to explain the sponge’s relevance: the scale-specific network geometry of a sponge is roughly hyperbolic at a small scale. Then the material is cubic at medium scale. And at the scale where you look at it as flat (being a sheet with finite thickness) it is two dimensional.


Why Does DMT Feel So Real? Multi-modal Coherence, High Temperature Parameter, Tactile Hallucinations (link)

Why does DMT feel so “real”? Why does it feel like you experience genuine mind-independent realities on DMT?

In this video I explain that we all implicitly rely on a model of which signals are trustworthy and which ones are not. In particular, in order to avoid losing one’s mind during an intense exotic experience (such as those catalyzed by psychedelics, dissociatives, or meditation) one needs to (a) know that you are altered, (b) have a good model of what that alteration entails, and (c) that the alteration is not strong enough that it breaks down either (a) or (b). So drugs that make you forget you are under the influence, or that you don’t know how to model (or have a mistaken model of) can deeply disrupt your “web of trusted beliefs”.

I argue that one cannot really import the models that one learned from other psychedelics about “what psychedelics do” to DMT; DMT alters you in a far broader way. For example, most people on LSD may mistrust what they see, but they will not mistrust what they touch (touch stays a “trusted signal” on LSD). But on DMT you can experience tactile hallucinations that are coherent with one’s visions! “Crossing the veil” on DMT is not a visual experience: it’s a multi-modal experience, like entering a cave hiding behind a waterfall.

Some of the signals that DMT messes with that often convince people that what they experienced was mind-independent include:

  1. Hyperbolic geometry and mathematical complexity; experiencing “impossible objects”.
  2. Incredibly high-resolution multi-modal integration: hallucinations are “coherent” across senses.
  3. Philosophical qualia enhancement: it alters not only your senses and emotions, but also “the way you organize models of reality”.
  4. More “energized” experiences feel inherently more real, and DMT can increase the energy parameter to an extreme degree.
  5. Highly valenced experiences also feel more real – the bliss and the horror are interpreted as “belonging to the vibe of a reality” rather than being just a property of your experience.
  6. DMT can give you powerful hallucinations in every modality: not only visual hallucinations, but also tactile, auditory, scent, taste, and proprioception.
  7. Novel and exotic feelings of “electromagnetism”.
  8. Sense of “wisdom”.
  9. Knowledge of your feelings: the entities know more about you than you yourself know about yourself.

With all of these signals being liable to chaotic alterations on DMT it makes sense that even very bright and rational people may experience a “shift” in their beliefs about reality. The trusted signals will have altered their consilience point. And since each point of consilience between trusted signals entails a worldview, people who believe in the independent reality of the realms disclosed by DMT share trust in some signals most people don’t even know exist. We can expect some pushback for this analysis by people who trust any of the signals altered by DMT listed above. Which is fine! But… if we want to create a rational Super-Shulgin Academy to really make some serious progress in mapping-out the state-space of consciousness, we will need to prevent epistemological mishaps. I.e. We have to model insanity so that we ourselves can stay sane.

[Skip to 4:20 if you don’t care about the scent of rose – the Qualia of the Day today]

Further readings:

“The most common descriptive labels for the entity were being, guide, spirit, alien, and helper. […] Most respondents endorsed that the entity had the attributes of being conscious, intelligent, and benevolent, existed in some real but different dimension of reality, and continued to exist after the encounter.”

Source: Survey of entity encounter experiences occasioned by inhaled N,N-dimethyltryptamine: Phenomenology, interpretation, and enduring effects

That’s it for now!

Please feel free to suggest topics for future videos!

Infinite bliss!

– Andrés

The Symmetry Theory of Valence: 2020 Presentation

Presentation Given at the Centre for Psychedelic Research at Imperial College London by Andrés Gómez Emilsson (December 8th 2020)

 www.qualiaresearchinstitute.org

Transcribed with otter.ai. Edited for grammar and clarity by Mackenzie Dion.

Watch the talk on our Youtube channel.


So, the Symmetry Theory of Valence. Just defining terms so that we’re all on the same page. There’s this thing called core affect which is basically what you get when you apply dimensionality reduction techniques to any one of many areas of psychology. There’s a surprisingly robust pair of dimensions that emerge in co-occurrences of words or even descriptions of behavior. These two axes, arousal and valence, seem to account for about 60% of the variance in terms of what information emotional words contain. And I mean, roughly speaking, arousal is the level of activation, how energetic you are, and valence is how good you feel. Most of what I’m going to be talking about is valence. That said, you need to also consider arousal in the picture to know what this is all about. Just a few examples: you have high arousal, high valence, so that would be kind of excitement and anticipation. But you also can have high energy, but not feeling really good, and that would be kind of anxiety or anger or irritation. Likewise, you have depression, which is low arousal, low valence, and serenity is peaceful, blissful calm, that would be low arousal, high valence. 

This is just one example of one of the ways in which you can recover these dimensions of valence and arousal. This was a little study we conducted years ago. We were studying people who have experiences with all kinds of substances online. We were giving them the survey, where they were going to describe a particular substance along something like 70 different dimensions. Then I conducted factor analysis on that data set. Interestingly, we have three core dimensions of valence or valence-related axes, which give you a sense of, okay, what is the space of possible effects that you can get from some substances. There were actually six dimensions that emerged, but three of them are valence-related:

We have slow euphoria, which is equivalent to low arousal, high valence with top terms like calming and relieving. The negative predictors of it would be something like anxiety, producing difficult bodily discomfort. Fast euphoria is the sort of thing you get with stimulants, you know, energizing, sociable, the opposite of feeling spaced out and confused.

The other axis that kind of emerged was this notion of spiritual euphoria. That’s the term I used back then. I also used the term significance, or saliency nowadays. Now I would actually use the term criticality for other reasons that we can go into. There’s this other kind of axis for how you can experience intense valence with substances, which is different from slow and fast euphoria, which would roughly correspond to the psychedelic space. And that, you know, gets marked with things such as mystical, incredible, life changing. The opposite of that is trivial, self-centered, or irrelevant or something like that. This is just to complete the cube. And, you know, in a sense…

This is just a kind of change of basis, where you still get, in a sense, the valence dimension emerging out of this dimensionality reduction analysis. If you were to apply just one dimension, you know, if you ask the factor analysis to just give you one factor, it is going to be the valence factor. That’s the axis that accounts for most of the variance for the effects of drugs.

I’ve got to say that I absolutely acknowledge that emotions are far more complex and intricate than just valence and arousal. This is the result of my master’s thesis where we were analyzing this thing called mood updates, how people feel over time, day after day. I was computing the transition probabilities between emotions, and you can do cluster analysis here and finding attractors. You’ll see that there’s additional information. That said, we concluded that a big chunk of the additional information that is not valence and arousal is actually information about your trajectory in the valence arousal space. For example, we found there would be emotions that because of what they tell you about your emotional dynamics we called gateway emotions, like feeling relieved and feeling hopeful. These terms contain information that you were in a negative, kind of depressive attractor, and you’re moving towards the positive high arousal attractor. In essence, the terms we use for emotions give you not only information about where you are in the valence-arousal space but also what is your trajectory in that space. But in a sense, valence and arousal still account for a very, very big chunk of what an emotion is. Okay, so hopefully I’ve convinced you of the importance of valence, at least in this context.

Now, let’s jump into the Symmetry Theory of Valence (STV). The overall hypotheses and the first explicit argument for it appeared in this really, really awesome work by my collaborator, Michael Johnson, Principia Qualia. He has a really interesting skeleton of an argument that points to a lot of research threads that are really worth getting into. I highly recommend digging into this work.

One of the things that it lays out is the kind of conceptual framework to make sense of what type of thing valence might be. I’ll just define a couple terms, which is, first qualia formalism. If there’s one thing at QRI we are married to, you could say, it would be qualia formalism. That is, for any conscious experience, there exists a mathematical object isomorphic to it. We can make an analogy here to something like electromagnetism where we used to have lightning, and electricity, and magnets, and all of that seemed sort of somehow thinly related. But, it turns out that there’s actually just four equations of electromagnetism that tie together all of that phenomena. And you can compare it to something like élan vital, the essence of life. People used to think that maybe there is some kind of a substance that determines whether you’re alive or not. And we would say that, well, that kind of fell through, you know, in the end there is molecular complexity under more molecular complexity. There doesn’t seem to be such a thing as “life itself”. Life is not formalizable in the same way as electromagnetism is, but something that we would claim at QRI or we could even say something that we assume at QRI, because we believe it is a very generative frame, is that yes, there will be a set of deep mathematical structures to consciousness. In particular, if you expand this into other areas, we also think this is going to apply to valence: that there is going to be a deep and rich mathematical structure to valence, and that notion is called valence structuralism.

In Principia Qualia by Mike Johnson, he has this argument for it, which I definitely recommend reading, especially if you have the aesthetic of a physicist. I think you’ll really like this work, because I think it’s really, really good in that sense. What I’m going to do now is try to give you a kind of intuition for it. And then the whole empirical argument.

Importantly, there are a lot of theories of what valence is. Mike looked at the literature, did a very deep dive into it, and realized that they’re usually unsatisfactory, or at the very least, they don’t get at the true core of what an explanation for valence should be like. So basically, you have these accounts of, for example, valence sees how the brain represents value. Ultimately, that’s just a correlation. Value is a fuzzy abstraction. Some people think valence is the presence of opioids in the brain. But if you inject opioids in different parts of the brain, it doesn’t always feel good. It actually needs to be injected in a very narrow range of stripes in the pleasure centers, and otherwise, it just causes strange feelings or wanting, but it’s not the signature of valence itself. Or, for example, the pleasure centers. Just because you’re calling something “the pleasure center”, and it’s correlated with feeling good, it doesn’t mean you have an explanation. It’s not a very insightful, illuminating, account of valence. 

So what could it be? I’ll focus to a large extent on what we are going to call bliss, which is just very positive valence. What is that? What is very positive valence? What is the sense of ecstasy, bliss, intense happiness? There’s a lot of intuitions. Definitely a lot of people think it’s some kind of spiritual signal, and I wouldn’t want to convince you out of that view. But the truth is that there are a lot of different spiritualities, and they sometimes say contradictory things. So it’s kind of strange to expect that there’s this underlying universal spiritual signal that whenever you’re doing something aligned with spirit, you feel good. Because sometimes you can do something very different than somebody else and still have that feeling. Also, the idea that it is “merely” chemical reactions in the brain, again, is not a super satisfactory explanation… same as with pleasure centers, health, few prediction errors, etc. Well, and in the end, I add, yes, symmetry and consciousness, which is what I will be arguing.

I also want to point out, and this is super important, that valence is not the same as healing, and it’s not the same as meaning. However, they’re correlated. I would also go as far as to say that high valence is necessary for healing and for meaning to a large extent. In a sense, you can have a lot of very high valence states that are actually very unhealthy for you. Just an example would be methamphetamine. It can feel great, but it’s unsustainable. To the extent that your nervous system is self-organizing around that high valence experience, it makes it kind of the center of your life. And, you know, it’s a dopamine releaser. It’s obviously unsustainable. You can’t actually do that long-term and expect good results. Whereas, something like meditation, or even psychedelics, because their tolerance mechanism is very, very different. You could say that, yeah, those might be high valence, highly meaningful, and also healing experiences.

So I just want to say that, you know, high valence doesn’t entail healing. And that in that sense, you might say, “Okay, why are we so interested in this?”, but I would say that high valence is a necessary condition for deep healing. And I would even go as far as to say that, for a psychedelic experience to be deeply healing, it has to involve high valence in one context or another. Of course, you may end up processing a lot of very difficult emotions. But ideally, it would be something that basically allows you to heal those difficult emotions and transform them into a state of mind that has many more of the positive qualities. 

And more so, high valence, even according to the Buddha, is an important factor for awakening. Of the seven factors for awakening, I would actually say about five of them are very connected to valence. Mindfulness, joy, relaxation, concentration, equanimity; they are kind of different flavors of high valence. They’re different ways in which a very high valence experience can manifest. The Buddha says that these are important things. Even if you only care about awakening, enlightenment, you may also care about the mathematics of valence. It might point you in the right direction as well.

I’ll also mention, there’s a big difference between the recipe of a state of consciousness and what you might call the review, or the description, of that state of consciousness. I’ll make an analogy with cooking: if you have cooking instructions for how to make a cake, sometimes it’s very counterintuitive what the cake is going to taste based on those instructions. Like “add yeast” for example. A lot of things in the recipe you may not know exactly how are going to actually affect the result. So, the recipe may look very different from the review of the state. I would say that for a lot of meditation states, or even just general life advice, this idea of don’t mindlessly chasing pleasure or trying to satisfy all of your existing desires compulsively gives counter-intuitive results. Yeah, chasing pleasure compulsively is not going to result in a sustainable high valence. To some extent, a lot of meditation instructions tell you to neither approach nor withdraw from emotions to develop equanimity. Since you are not engaging with your emotions, it sounds like the result is a fully neutral experience, right? It sounds like it’s unrelated to valence, almost cutting out the valence. But I would say: that’s just the recipe. Those are the instructions for how you manage your attention in order to eventually change your brain to actually generate these very healthy, sustainable, high valence states. So I definitely want to overcome this prejudice of thinking that high valence is unrelated to spirituality. No, I think they’re actually very deeply, intimately connected. 

Okay, so let’s go into the Symmetry Theory of Valence. I’ll just read these, but we will go into more depth into all of these. So, you know, we talked about qualia formalism, there is a mathematical object whose features are isomorphic to phenomenology. We believe that, yeah, harmony basically feels good because it’s symmetry over time. And basically, there’s kind of this duality between symmetry and space and synchrony in time. We will go over pleasure centers. The way we explain pleasure centers in this theory is that they are kind of tuning knobs (this was first proposed in Principia Qualia). They are there these bridges that, basically, when they get activated, they enable global large-scale synchrony in the brain. This is something that ultimately is very testable. Because if you can activate the pleasure centers, or inhibit whole brain harmony, we predict that’s going to actually negate the positive valence effects of the pleasure centers. Likewise, if we can induce large scale harmony, without activating the pleasure centers, or maybe even inhibiting the pleasure centers, we expect that to be a high valence state. So, it’s a cool, testable interpretation of what pleasure centers even are. 

Boredom is kind of an anti symmetry mechanism. So that’s why even if you look at a cathedral or something like that, you’re not going to be happy forever. You’re going to be happy for a little bit. Because your brain realizes that you’re not learning anything, and adds kind of this dissonance in order to make you move on to something else. We are wired in such a way that what helps us reproduce symmetrifies our consciousness. So, it’s not that high calorie food in and of itself is symmetrical, it’s not that it in and of itself is pleasant. It’s more that the way our nervous system is programmed is such that when you eat high calorie food, it triggers high valence. And that triggered high valence is what would be symmetrical, not necessarily the chemicals that you’re eating.

Importantly, valence, we think, has these three dimensions, which is positive, neutral, and negative. And you can actually have highly mixed experiences. You can have experiences, I don’t know, an example is you’re at a concert, enjoying yourself, but also you have to go to the bathroom, and you just broke up with your boyfriend. You can have these very complex mixed valence experiences, where parts of your experience are very pleasant, parts are very distressing, parts of those are very neutral, and that’s fine. At the same time, it still kind of collapses into this ultimately, “Hey, are you having a good time or not?”.

And something that the Symmetry Theory of Valence would say, and this is a pretty interesting kind of relationship, and I’ll explain it in a couple slides. This is just to kind of put it out there in your head to bounce around as we go on, which is that we expect there to be a very, very intimate relationship between information content, and basically the range of valence that you have access to. So in brief, for very, very high valence states of consciousness, we expect those to have very close to zero information. Whereas, when you have this state that is close to pure white noise, we expect that to be basically zero valence. Hopefully, this will make more sense as we go along.

These are just some illustrations of this principle. Actually, we expect that some of the most negative experiences out there will actually be pretty close to very, very highly symmetrical. I put this disjointed lattice at the bottom. And I would claim that something like a bad 5-MeO-DMT experience is actually something that is very regular, except for some strange disjoints, or imperfections, that cause profound dissonance. Whereas, if you’re in the pure noise kind of range, it all feels blah, it all feels really close to neutral.

When we say the state of consciousness is highly symmetrical and such, you know, let’s say, 5-MeO-DMT, or jhanas, or something like that, we expect these to actually show up in many ways. If you look at the biorhythms, like heart rate and breathing, that’s going to show up, symmetry is going to show up in some ways, being a different kind of projection of the latent state. I mean, ultimately, the formalism, you know, this mathematical object corresponds to consciousness is not observable directly, at least not right now. So we have to kind of rely on these projections, these interpretations of what’s going on, these ways of getting at this unobservable, underlying state. And EEG, connectome harmonics, biorhythms, and so on, are different ways of getting at it. I’ll show you at least empirically that it’s all so far consistent with the Symmetry Theory of Valence.

Here’s kind of the big plan. All of these different projections of this underlying state. So we have basically this stimulus. These are kind of visualized also to give you an intuition. So there’s stimuli, basically more symmetrical stimuli with higher valence, then there’s the endogenous bodily state, you know, biorhythms, as well. The CNS State, the actual, okay, what’s going on in your brain, then the formalism, and then the phenomenology of valence. When you have high valence, we expect (and what we see is) that there’s symmetry all across the board, in each of these different ways of looking at the state of consciousness. In each of these projections of the latent state.

So I’ll go on and start with phenomenology. I know that phenomenology is such a tricky thing. It’s so difficult to do, right. It’s so difficult to do. You make a lot of mistakes in phenomenology, get confused, and become self-deceived. So I mean, hopefully, the observation I’ll relate to you is going to show you that at least we’re taking care of some of the failure modes of phenomenology.

So, first of all, we distinguish between intentional content and phenomenal character. So, if you smoke DMT, and you experience, you know, you say something like “I saw a dragon with my own eyes” that doesn’t mean there was actually a mind-independent dragon out there. And, you know, I take seriously your report that you saw a dragon, but I don’t know how significant that is necessarily. On the other hand, if you describe “Oh, and by the way, the dragon had scales that had a symmetry group of what’s called the glide mirror symmetry group, and it had a 17 hertz strobing effect“. Okay, yes, so we’re getting more into the phenomenal character. You’re actually describing what it felt like, not only what it was about. I would make the claim that these observations of symmetry being related to valence are about the phenomenal character. I don’t care that much about, you know, “What was the journey? What was the content of the experience?” I care more about what it felt like, what are the features of it, and what we observe is that there’s a deep connection here.

So I’ll just give you some examples. Basically, introspect. You know, the difference between massage and bodily pain. Massage is kind of this very, very pleasant, harmonious, tactile pattern throughout your body that gives you these very nice waves of pleasure, as opposed to bodily pain. Bodily pain, if you introspect on it, it’s almost kind of like there’s like pinch points and discontinuities and fragmentations and deformations in your sense of self and the continuity of your skin or your felt sense of your inner organs. Basically, I would make the claim that bodily pain always manifests in one way or another as a kind of symmetry breaking operation. Now, definitely keep this in mind if you ever have a pain again, hopefully not.

Also, let’s say anxiety versus relaxation. Anxiety, you could almost describe it as, constant prediction errors. “Oh, did my heart do something strange? Is my leg positioned properly?”. It’s a state of mind where all of these little imperfections bubble up to your awareness. I would say it’s interrupting the flow of your attention and creating these pinch points and deformations in the way you experience the world. As opposed to relaxation, where you’re almost kind of just completely melted into it. And it’s so regular, you can almost filter out most of your bodily sensations. And in that sense I would argue it has a very symmetrical quality.

There’s also this whole argument Mike brings up which is the phenomenology concerning non-adaptiveness, the non-adaptiveness principle, which is that basically, there’s a bunch of things out there that feel really good, but that weren’t in our evolutionary environment. Those are hints; we consider those hints that hey, if something wasn’t in the African savanna but feels great, it probably means that it’s kind of directly hacking into the patterns of valence somehow. We didn’t evolve to filter those out or to not get absorbed by them. And yeah, here are some examples, but I’ll go deeper into those. 

Now, there’s also this exotic valence. Bodily pain, anxiety, relaxations: those would be examples of “normal valence”. It’s the valence that we’re all used to. But I would say that also in “strange valences”, like valences in weird states of consciousness, they also follow this pattern. That in some sense, symmetry explains their pleasantness. And I’ll give you some examples.

So, dream music. I’ve had the pleasure or displeasure, you could say, of having had a lot of sleep paralysis and lucid dreams, and this effect is something you can experience in either sleep paralysis or lucid dreams. If you’ve had a lucid dream, where you were making music, or you heard, you’re hallucinating that there was a radio playing, you will notice that, “Oh my gosh, the music can be beautiful, like… incredible”. And this music, maybe you have heard it before, maybe not. Maybe your brain is generating it on the fly. But it has a quality to it that is extraordinarily hedonic and pleasant. And I remember studying this on myself over many lucid dreaming experiences. At first, I thought, “Oh my gosh, my brain is just unlocking this ability to create awesome harmonies and melodies”. But then I ended up realizing that even if I just make a kind of an “om”, this meditation sound, even though that sound is extremely simple, the quality of the sound in the lucid dream is profound. I mean, it’s almost kind of a surround sound, like 360 surround sound, and stereoscopic and full of reverb and richness. 

I would claim that it’s actually because, during a dream state, your brain is more resonant. You can kind of enter into these very, very resonant attractors, and it’s that quality that makes the music so compelling, not the melody. If you transcribe the melody, the melody may not be very significant. It was how it sounded that was so profound in the music in the dream.

Then you have meditation. Even these images, maybe, I don’t know if this is cheating, but representations of meditation, like high attainments, and so on, they usually come with these beautiful symmetries and whatnot. If you examine the phenomenology of jhanas, how they’re described, there seems to be kind of this projection of less and less information content in your experience. Going from having all of your attention concentrated in one point to then the experience of completely perfectly smooth, boundless space to then just pure consciousness, and then the experience of neither nothing nor something. In a sense, that’s kind of approaching the limit of zero information. And then people report these jhana experiences, they’re not pleasant in a conventional sense. It’s not like eating ice cream or something like that, but they’re still very, very high valence. They’re blissful, in an exotic way. But, I do want to point out that there’s this fascinating, strange relationship here between low information content and the blissfulness and the healing quality of the state.

And then there is exotic valence from psychedelics. I mean, again, I don’t want you to focus on the intentional content, what was the experience about. What you thought, of course, can influence your valence, but it’s more about the phenomenal character. There’s this phenomena of tracers, you move your hand around, and you see copies laying around, and in a sense, it’s giving a temporal depth to your experience. It’s almost kind of adding a new dimension of time, where qualia can pile up. And usually, if the trip is good, you’ll notice that these tracers are in a harmonic relationship with each other. That is kind of the essence of what makes them feel so good.

Likewise, there’s a psychedelic texture repetition. You stare at a piece of grass on LSD, and it starts to symmetrify. And I would totally say this is exotic valence because you ask the person, and they will say “the ground was symmetrifying, and I don’t know why, but it was awesome”. There was something really cool about it, and why would that be? Our interpretation here is that psychedelics are, in a sense, unlocking the valence capacity of your visual cortex. It’s kind of transforming your cortex into a pleasure machine, basically allowing it to exhibit these profound symmetries, and that is what actually is making them feel so compelling. People will struggle to explain “Why were the visuals cool? Why were they interesting?”. When it comes down to it, I think it is the symmetry.

Interestingly, these are called the wallpaper symmetry groups. There’s 17 possible ways of tessellating a two dimensional space. From subjective reports, we know that any of these can be experienced on a psychedelic. The ground, kind of chaotically, will arrive at one attractor of symmetry. It could be any of these 17, and they all feel great. They’re all extremely aesthetic and beautiful and blissful in one way or another. But it’s kind of a testament to just how general this effect is.

I would make the claim, and this is obviously a strong claim, but it matters for something like therapy, psychedelic therapy. We recently saw this fascinating research on psilocybin for major depression, and that a lot of these effects are mediated by whether you had a mystical experience or not. I would say that if you did have a mystical experience, and it was healing, I would bet that while you were having that experience, the sense of space and time was basically extremely, extremely symmetrical. And here is kind of why it’s so confusing. Because you come back and you say, “Well, I saw Jesus”, and you think that you got healed because of Jesus. I don’t want to dissuade you from that view, but I would basically ask you “Okay, but when you experienced Jesus, what was the feeling of space and time?”. They might say something like, “Oh, it had a beautiful light. It had this beautiful harmony and rainbows”. And I’ll claim that if you introspect on them then that it’s actually the quality of phenomenal space and time that is healing and blissful. The meaning, the religious meaning, is something that is helping your mind basically concentrate on that space, and take it seriously as a way of propagating this negentropy in your nervous system.

Now, another place where this shows up super, super clearly, phenomenologically, is on DMT. I definitely recommend this article we wrote that basically charts the DMT space. You can know a lot about where you are in the DMT space by describing what is your energy level on the one hand, and then what is the information content on the other. I would say DMT states that have close to zero information content would be kind of these geometric, perfectly repeating, symmetry groups, either 2D or 3D. Whereas, more chaotic states would be kind of in the middle. The energy level would be a matter of dose. The “height” you reach is very, very dose-dependent. But then the valence, I think it’s very, very dependent on actually where in the axis of information content you find yourself in.

Here again, there’s this diagram that the most blissful experiences you may have on DMT are going to be on these kinds of honeycombs and perfectly symmetrical patterns. The most unpleasant experiences are going to be just right next to those, they are going to be kind of dissonant honeycombs. Whereas you know, when you get to complex narratives, like machine elves and alien realms and all of that stuff, those experiences would be very mixed in their valence. There’s both dissonance, consonance, symmetry, anti-symmetry; those are very complex experiences.

Now, the information content, we think of them as basically attractors in feedback systems. You may end up in a chaotic attractor, you may end up in a limit cycle or a fixed point. And that will determine how much information content the state has. 

Interestingly, this also can be used to describe the difference between DMT and 5-MeO-DMT. We think DMT tends to have a lot more information content. 

So you have these very rich patterns, and I would say competing synchronies. On DMT, there’s all of these slightly different frequencies that are competing for your attention and creating a narrative out of that. That is like a very mixed experience; it is both blissful and distressing at the same time.

Whereas 5-MeO-DMT, which is described as far more powerful emotionally, tends to give you this sense of pure space, like the feeling of the insight into emptiness, the feeling of infinite boundless consciousness, very little information content. Yet, it’s so emotionally impactful to such an extreme extent.

Interestingly, I would say, the reports do come out that on 5-MeO-DMT, you may have the best experience of your time, or you may have the worst experience of your life. It’s kind of bimodal. It’s either amazing or it’s extremely bad. Often, it starts out really bad and then it gets amazing. I would describe that in terms of kind of this annealing process where it basically starts with dissonance, and, over time, things synchronize, and you do end up where all of your nervous system is entrained to the same frequency, and that feels very, very blissful. Whereas DMT is always kind of in this mixed state. It is very difficult for DMT to be pure negative or pure positive. It’s always this mixed state. So I would say, yeah, this is kind of the phenomenological case for the Symmetry Theory of Valence.

I’m two thirds of the way through the presentation. I’m just gonna walk you through the empirical evidence. So we were talking about phenomenology; that’s one of the projections of this formalism and its symmetry. There’s symmetry in the formalism. It’s gonna manifest in some forms of phenomenological symmetry. Likewise, you know, if you use external stimuli in order to generate a state, like, let’s say, watching a movie, playing music, playing stroboscopic stimulation, there’s a lot of evidence that indicates that the symmetry of the stimuli is the leading factor for how pleasant or unpleasant the resulting state is. We have all of this research in vision.

These are just some examples. It’s so stunning, right? Even if you know the effect, you still get the valence response. You go to a cathedral and think “Okay, I’m not gonna get high valence, I’m not going to get high valence”. You still get the response. It’s pretty automatic. As long as it has this rich, deep symmetry, oftentimes, it’s going to be very beautiful. There’s something very compelling about this.

Just some random pictures to give you a sense of this.

Why does this feel good? It really has very little to do with our ancestral environment.

Anyway, this is such a robust effect that, with the symmetry of faces, for example, even face paint can be used to modify the valence. So, if you don’t have a perfectly symmetrical face, but you add symmetrical face paint with beautiful patterns, you’re going to be judged as more beautiful. It’s just such a strong effect, that it can actually modify your perception of how beautiful somebody is. Likewise, if you add asymmetrical patterns, you look less beautiful. Now, this, I wouldn’t say this is that strong of evidence because this actually does have an evolutionary reason. Symmetry in faces is a marker of mutational load. So I don’t put that much stock in, symmetry of faces being that relevant. But symmetry in other forms is where I think it’s so stunning. 

You also see this in symmetry in audio, basically, regular rhythms. Harmony is the leading predictor for whether a sound is going to be pleasant or unpleasant.

You know, this is Helmholtz’s big idea. He was the first one to figure out why playing two notes in a piano that are one semitone apart feels unpleasant. It’s because the harmonics are basically within what’s called the critical window. They generate beat patterns and the beat patterns can be described as basically symmetry breaking operations in the waveform. Those symmetry breaking operations, in essence, cause irritation. So basically, the more beating there is in sound, and the more beating across the spectrum, the more irritating and distracting and rough the sound is going to sound like. Whereas, when you have these harmonic relationships, you play one note, one piano note, and another at an octave of difference, the harmonics line up perfectly. Actually, the sound is very compressible because you don’t have this extra information of where all the other harmonics lie. They’re just the harmonic sequence. And that is universally described as a more pleasant sound.

When you add up all the harmonics, you get these interesting curves. The height here is the amount of dissonance. When you have a relationship of one to two, basically an octave, you have zero dissonance, and that feels really good. Now, music is very complicated. We have to factor in the boredom mechanism. If you just play the same octave over and over, you get bored, and there’s an inner sense of restlessness and dissonance. But if you just hear it for the first time, then there’s a super, super strong relationship between symmetry and valence.

These are just examples of a piano chord.

Dissonant sounds. I can send you a link to all of these sounds after the presentation*, but I have some links for a SoundCloud account where you can kind of get convinced that “Oh gosh, these are actually really bad sounds”. It’s not that I’m saying they’re bad. If you ask 100 people, like 99% of people will say they’re awful. 

Likewise, reverb basically symmetrifies any waveform. Reverb is almost kind of this hack that you take almost any dissonant sound and you add reverb to it and is going to sound a lot less bad, a lot less distracting, irritating, and so on. So this is comparing the sound of a baby crying, which by the way, like in our analysis, it shows that babies crying, it’s almost like their sound is optimized for dissonance. It’s almost kind of as dissonant as it gets for a sound made by a human. For good evolutionary reasons, it has to be distracting, and catch your attention, bring the desire to stop it. But you add reverb and to give you a sense, that’s like if the baby was in a huge cave, you get all these echoes averaging out the beat patterns. It sounds way better, way less distracting, probably not good from an evolutionary standpoint. But, it’s just a fascinating kind of transformation you can apply to any waveform.

And here, I just want to illustrate that valence can happen across the spectrum. So I also have this file**, and you’re welcome to listen to it after the presentation where you can have consonance anywhere in the spectrum, mixed in with dissonance anywhere in the spectrum, mixed in with noise anywhere in the spectrum. That ends up basically creating these very mixed states. 

So basically, when I say “Oh, I had a mixed experience, a mixed valence experience” that underdetermines what I experienced because we don’t know if the positive part was in the high frequencies or in the low frequencies. We don’t know that. That’s why the full picture of valence would also include the spectrum for positive, negative, and neutral valence. You can have high frequency pleasure, you can have low frequency pleasure, etc. So that kind of explains why there’s a tremendous diversity of possible mixed experiences even though ultimately they’d still come down to symmetry. Deep down, they can all still be explained with symmetry.

Now, endogenously generated symmetry, this is fascinating research. That when you have this “biorhythm coherence” you feel happier. And the way of computing biorhythm coherence is very related to musical consonance. Breathing entrained with heart rate variability is reported as giving rise to a just much, much better positive mood, and is one of the things that long-term meditation achieves. Meditation entrains these biorhythms and basically makes them interlock with one another. That is reported as giving rise to positive mood which is an interesting finding and very consistent with STV.

Here are just some quotes. Cool.

And you know, the heart palpitations. I mean, it’s similar to anxiety in that if you have like this usually regular metronome, and it’s failing, is generating these imperfections, that gives rise to unpleasant states of mind. I’m sure heart disease is terrible for your valence. Likewise, meditation is a wonderful tool for heart disease because it allows you to overcome those imperfections and still feel good despite the problem.

In terms of other endogenously generated symmetry, I will mention orgasm and flow. Orgasm is a powerful generator of endogenous resonance. It’s the entrainment of motor systems to near hallucinations, to synchronizing feedback processes across multiple functional networks. With an orgasm, there’s a deep, deep level of synchrony and symmetry across the nervous system. I highly recommend introspecting on this (not to get into your sex life or anything, though). I mean, it’s something you can actually pay attention to, and it becomes very obvious once you notice it. 

Likewise with flow, there’s this evidence that symmetry is deeply related to flow. Two physiological metrics for measuring flow are cortical muscular coherence and a degree of coupling between neural EEG waves and EMG oscillations of muscle activity. So, there’s also these interlocking patterns, lower information content, more symmetry. Yeah, it’s a strong predictor of flow. So like, hey, go figure flow is also symmetrical.

Okay, let’s get into the symmetry in the brain. So this is kind of the other projection you could take of the latent state. If you look at the central nervous system of high valence states, how does the valence show up? And, you know, meditation, like all over the place, basically pretty much any kind of meditation, if done for a long enough time, leads to some kind of EEG coherence. Whether it’s gamma coherence, delta coherence, or alpha coherence, depends on which kind of meditation you do. But they all generate some form of coherence, and coherence in EEG is intimately related with symmetry. I mean, basically, two signals are coherent when they’re both reflections of a shared signal through a reverb pattern, meaning that they’re encoding the same information just through a different filter, which is, again, deeply, deeply connected to symmetry. 

Here’s a fascinating study from 2019 that I recommend reading which to me was really stunning. It was stunning in just how clear the connection with the Symmetry Theory of Valence was. The study is about the EEG recordings of the first and second jhanas and the interesting patterns that emerged in them. One of them is this seizure-like activity. Now, seizure-like activity is three to five hertz, and it doesn’t have harmonic structure. I mean most seizures don’t have their harmonics together with them. But the type of seizure-like activity you see on jhanas does have harmonic structure. And the picture here is basically the Fourier transform of the independent components of the EEG recordings. You can see there’s a very clean 5.6 hertz signal, together with its harmonic of 11.23 hertz. This is kind of stunning. Why would this happen? And jhanas feel really blissful. Without the Symmetry Theory of Valence, this is just super surprising and strange. With the Symmetry Theory of Valence it’s like, “Oh, yeah, you’re, feeling a really great symmetrical attractor of your brain and sustaining it”. So that’s going to feel good. 

Even you know, ketamine showing high levels of a gamma coherence.

For 5-MeO-DMT, the only dataset I’m aware of, of EEG and 5-MeO-DMT, shows coherence across the spectrum, not only gamma coherence, but also beta coherence, and especially delta coherence. Again, why on earth? The Symmetry Theory of Valence would explain this. It would say, “Yes, this is expected”. Other theories might struggle a bit. Now, I’ve got to say that just because you have high coherence doesn’t mean it’s going to be high valence. We expect also very negative valence could also be high coherence. Except that when you have total coherence, then we expect that to be always positive valence. Again, it’s going to have that relationship because you could still have a high average coherence, but have half of your channels coherent in a certain frequency and half of the other channels coherent in a slightly different frequency. That might actually maximize dissonance. So just average coherence is not enough. You also need to tell whether it’s in harmonic structure or not.

Pleasure in the brain seems to be kind of this distributed effect that also from our point of view would mean it’s actually a whole brain phenomena. 

This is about what I was mentioning about the pleasure centers from our point of view. I mean, there’s this research of if you tried to synchronize clocks, and you tried to synchronize neurons, and you put them in a geometric grid. If it’s large enough, you’re not going to usually get full scale synchrony. You might have emergent patches of synchrony or traveling waves of synchrony. But if you also add these random connections across the network and reduce the synaptic path length, then you can unlock the ability for the entire network to enter synchrony. So we think of the pleasure centers as kind of these bridges that are, in a sense, lowering the average synaptic path length across your brain, and therefore enabling similar synchrony across the brain. And that’s the reason why we think the pleasure centers generally feel good when you activate them. 

Okay, getting to the end of the presentation. So I’ll just talk about a few near “enemies”. I put “enemies” in quotes, because we actually admire these people. They’re part of our research lineages. I think they’re a very, very key component of any good theory of consciousness. But I think when it comes to valence itself, there’s some explanations in the space that are really close to the Symmetry Theory of Valence, but they’re not exactly what we’re getting at. So there’s this whole account of computational efficiency. The brain likes computational efficiency, but in a sense, you still have to explain why the brain likes computational efficiency- what does this liking manifest as? We use this argument of “passing the bucket” which ideally your theory of valence should avoid. The theory should explain what valence itself is, not only when it gets triggered. These theories of computational efficiency, energy efficiency, we would claim, they’re telling you under what conditions positive valence gets triggered, but they don’t tell you what positive valence itself is. And that’s what the Symmetry Theory of Valence is getting at. 

So yeah, these are some of the issues with those, at least as complete theories.

Finally, okay, counter examples. There’s this whole theory I recommend reading called Neural Annealing (by Mike Johnson). But even very neutral energy that neither has harmony or dissonance, can still give rise to very positive feelings because it can give rise to this annealing process. And that’s actually what we believe is going on with psychedelics. Psychedelics gives you what Mike would call semantically neutral energy. And that gives rise to basically this entropic disintegration, a term from Robin Carhart-Harris and the entropic brain hypotheses, which then gives rise to kind of this search, or self-reorganisation that basically will settle on these basins of symmetry. And it’s those that feel good, not the energy that feels good. It is the end result, the attractor that it takes you to.

And this explains, I think, why even somebody can like hot sauce. Hot sauce is kind of this unpleasant stimuli, but it can lead to euphoria. It can lead to this heightened state of energy. If you introspect on the euphoria of hot sauce, it’s not the unpleasant pain in the mouth, it’s that it raises all of your energy, your entire amount of the intensity of your consciousness. You can then notice these resonant waves, and it is those resonant waves that feel good, not the hot sauce itself. So there’s this kind of a step that basically separates one from the other.

I’ll just very quickly, briefly describe one way we’re trying to test the Symmetry Theory of Valence. It is not the only way to test it. I would even argue that, you know, the argument that I here presented is itself a potentially strong argument. But ideally, you know, we generate novel predictions. And this is one of them, which is that we basically expect that the very positive states of consciousness will have a harmonic relationship, basically a consonant relationship between the brain harmonics. Yeah, using the work of Selen Atasoy.

This algorithm of quantifying the amount of consonance in brain harmonics, which is something we were working with, and hopefully will get resolved soon.

We anticipate that, again, if this is true, the Symmetry Theory of Valence would be validated. If it’s not, it doesn’t invalidate it, because there’s many ways in which it can manifest. But when you have harmonics that are in a consonant relationship with each other, and those are the main drivers of your experience, we expect that to be pleasant.

That is, euphoric.

Whereas, when you have harmonics that are dissonant with each other, they generate these intense beating patterns. So we expect that to be described as unpleasant. Again, we don’t know, but we want to check if this is true. 

Just a couple testable predictions based on this, which is that we expect psychedelics to enhance the range of valence. Basically, psychedelics enhance energy across the board. Just all of the harmonics have more energy. We expect that some of those combinations will be just very consonant and reported to be very pleasant, some of those will be very dissonant, reported to be unpleasant. Then SSRIs, there’s a lot of research on SSRIs and their blunting effects. They cut the extremes of valence. So, we expect when it comes to harmonics that the SSRIs will be more noisy, less consonant, less dissonant. MDMA, we expect it to be a stable attractor of a few resonant modes that are very consonant with each other. Stimulants would be kind of high frequency consonance. Opiates would be low frequency consonance. Again, this idea that you can be in a good state leaves underdetermined whether there are symmetries in the high frequencies or the low frequencies, and this would disentangle these types of mixed experiences.

These are the last two or three slides which is kind of a case study which is SSRI’s. Roughly speaking, we interpret them as being noise inducers which is why things like orgasm on SSRIs are less intense. Crying is hard. I mean, crying itself is a kind of a dissonant and sometimes consonant, kind of resonant state. On SSRIs you feel kind of spaced out and music enjoyment goes down. So yeah, the way we think of SSRIs is that they’re almost kind of like listening to a white noise machine along your life, so it’s gonna cut off the extremes. It’s gonna blunt both very positive and very negative valence, and it’s gonna just kind of center you in neutral valence.

Whereas psychedelics, they basically kind of purify and intensify your harmonics. And in that sense, you get to have more pleasant and more unpleasant states and both extremes.

Just to remind you: introspect. I compel you, next time you’re on a psychedelic having a mystical experience, introspect on the quality of space and time. I suggest that you will probably be experiencing these kinds of beautiful ripples that are in a harmonic relationship to each other. Please email me if this is true or not true. But that’s the experience so far. And that’s the reason why this can feel so amazing. 

The future of mental health, ideally, would be that we can identify, “what are the sources of dissonance in your nervous system?” and then find the shortest path to the smallest change possible that will give rise to sustainable consonance in your nervous system. Whether this is going to be with meditation, a psychedelic session, or yoga, or biofeedback will be person-specific. There’s probably a shortest path from a highly dissonant dysfunctional state to a sustainable consonant state for each person.

And with that I just want to say thank you to other people in the team of QRI. And thank you, Robin, Shamil, and all of you guys for attending this presentation. And to the Centre for Psychedelic Research for hosting this presentation.

Thank you so much.


* BART sound, Baby Crying, Baby Crying w/ Reverb

** Consonance – Noise – Dissonance – Mixed Spectra


Special Thanks to: Mike Johnson who initiated this research direction and has been deeply involved in it for years. To Andrew Zuckerman, Quintin Frerichs, Kenneth Shinozuka, Sean McGowan, Jeremy Hadfield, and Ross Tieman for their contributions to the current work this year. To everyone in the team for their help, support, and love. To our donors for their incredible help. And to you, dear reader. Thank you!

Oscillatory Synchrony is Energetically Cheap

Excerpt from Rhythms of the Brain (2006) by György Buzsáki (pgs. 168-170)

The paramount advantage of synchronization by oscillation is its cost-effectiveness. No other known mechanism in the physical world can bring about synchrony with so little investment. What do I mean by declaring that synchrony by oscillation is cheap? Let me illustrate the cost issue first with a few familiar examples from our everyday life. You have probably watched leisurely strolling romantic couples on a fine evening in a park or on the beach. Couples holding hands walk in perfect unison, whereas couples without such physical link walk out of step. You can do this experiment yourself. Just touching your partner’s finger will result in your walking in sync in a couple of cycles. Unless your partner is twice as tall or short as you, it costs pretty much the same effort to walk in sync as out of sync. Once you establish synchronous walking, it survives for quite some time even if physical contact is discontinued. If both of you are about the same height and have a similar step size, you will stay in sync for a long distance. In other words, synchronization by oscillation requires only an occasional update, depending on the frequency differences and precision of the oscillators. Two synchronized Patek Philippe vintage timepieces can tick together for many weeks, and quartz watches fare even better.

A much larger scale example of synchrony through oscillation is rhythmic clapping of hands, an expression of appreciation for superior theater and opera performances in some countries. Clapping always starts as a tumultuous cacophony but transforms into synchronized clapping after half a minute or so. Clapping synchrony builds up gradually and dies away after a few tens of seconds. Asynchronous and synchronous group clapping periods can alternate relatively regularly. An important observation, made by Zoltán Néda at the Babeș-Bolyai University, Romania, and his colleagues, is that synchronized clapping increases the transient noise during the duty cycle, but it actually diminishes the overall noise (Neda et al. 2000).* The explanation for the noise decrease during the synchronized clapping phase is the simple fact that everyone is clapping approximately half as fast during the synchronous compared with the nonsynchronous phase. Oscillatory entrainment nevertheless provides sharp surges of sound energy at the cost of less overall muscular effort. The waxing and waning nature of rhythmic hand clapping is reminiscent of numerous transient oscillatory events in the brain, especially in the thalamocortical system. Similar to hand clapping, the total number of spikes emitted by the participating neurons and the excitatory events leading to spiking may be fewer during these brain rhythms than during comparable nonrhythmic periods. A direct test of this hypothesis would require simultaneous recordings from large numbers of individual neurons. Indirect observations, using brain imaging methods, however, support the idea.**

Perhaps the most spectacular example of low-energy coupling, known to all physics and engineering majors, is the synchronization of Christiaan Huygen’s pendulum clocks. Huygen’s striking observation was that when two identical clocks were hung next to each other on the wall, their pendula became time-locked after some period. Synchrony did not happen when the clocks were placed on different walls in the room. Huygen’s clocks entrained because the extremely small vibrations of the wall that held both clocks were large enough that each rhythm affected the other. The physical reason for synchrony between two oscillators is relatively simple, and solid math exists to explain the phenomenon.*** However, extrapolation from two oscillators to the coupling behavior of large numbers of oscillators is not at all straightforward. Imagine that, in a cylinder-shaped room, 10 clocks are placed on the wall equidistant from one another, each started at a different time. In a second, much larger room, there are 100 clocks. Finally, in a giant arena, we hang 10,000 identical clocks on the wall. As with Huygen’s two clocks, each clock in the rooms has neighbors on each side, and these clocks influence the middle clock. Furthermore, in the new experiment, there are many distant neighbors with progressively less influence. However, the aggregate effects of more distant clocks must be significant, especially if they become synchronous. Do we expect that synchronous ticking of all clocks will develop in each room? Various things can happen, including traveling waves of synchrony or local buildup of small or large synchronous groups transiently. Only one thing cannot occur: global synchrony.

I know the answer because we did an analogous experiment with Xiao-Jing Wang and his student Caroline Geisler. We built a network of 4,000 inhibitory interneurons.**** When connectivity in the network mimicked local interneuron connections in the hippocampus, all we could see were some transient oscillations involving a small set of neurons. On the other hand, when the connections were random, a situation difficult to create in physical systems, a robust population oscillation emerged. So perfect harmony prevailed in a network with no resemblance to the brain but not with what appeared to be a copy of a local interneuronal network. The problem was the same as with the clocks on the wall: neurons could affect each other primarily locally. To reduce the synaptic path length of the network, we replaced a small subset of neurons with neurons with medium- and long-range connections. Such interneurons with medium- and long-range connections do indeed exist (see Cycle 3). The new, scale-free network ticked perfectly. Its structure shared reasonable similarities with the anatomical wiring of the hippocampus and displayed synchronized oscillations, involving each member equally, irrespective of their physical distance. The reason why our small-world-like artificial network synchronized is because it exploited two key features: few but critical long-range connections that reduced the average synaptic path length of the network and oscillatory coupling, which required very little energy. Analogously, cortical networks may achieve their efficacy by exploiting small-world-like organization at the anatomical level (Cycle 2) and oscillatory synchrony at the functional level. There is synchrony for (almost) free.


* Most of the observations were taken in the small underground Kamra (Chamber) Theater of Budapest. Global and local noise was measured by microphones above the audience and placed next to a spectator, respectively. Rhythmic group clapping emerges between 12 and 25 seconds. Average global noise intensity, integrated over 3-second time windows, indicates decreased energy spending by the audience during the rhythm despite large surges of noise.

** The BOLD signal (see Cycle 4) decreases over large cortical areas during both alpha dominance (Laufs et al., 2003) and thalamocortical spike-and-wave epilepsy (Salek-Haddadi et al., 2002), demonstrating that the metabolic cost of neuronal activity associated with increased neuronal synchrony may, in fact, be less than during nonrhythmic states.

*** For the English translation of Huygen’s original letter about the “sympathy” of clocks, see Pikovsky et al. (2001).

**** In reality, the issue we addressed was quite different from the clocks on the wall because none of the 4,000 interneurons was an oscillator. Instead, their interactions formed one single clock (Buzsáki et al., 2004). Coupling of numerous oscillators have been analyzed mathematically, but these mathematical models lack the physical constraints of axon conduction delays; therefore, they cannot be directly applied to coupling of brain oscillators (Kuramoto, 2984; Mirollo and Strogatz, 1990). For the coupling of two identical oscillators with realistic axon conduction delays, see Traub et al. (1996) and Bibbig et al. (2002).


See also:

  • 5-MeO-DMT vs. N,N-DMT – Interestingly, 5-MeO-DMT seems to lead to global synchrony (and thus the melting of internal boundaries, the feeling of complete oneness with the universe) whereas N,N-DMT instead seems to give rise to powerful clusters of synchrony which are constantly competing against each other (thus creating partitions in the mind and the sense of “an other”, aka. machine elves). It would be fascinating to figure out why this difference emerges at the level of functional changes to the brain’s network topology as induced by each drug.
  • Modeling Psychedelic Tracers with QRI’s Psychophysics Toolkit: The Tracer Replication Tool – makes the case that psychedelic tracers may be a window into the brain’s network topology based on the rhythms they give rise to (which the tool seeks to rigorously quantify).
  • Neural Annealing – provides a model of emotional updating involving global synchronization via an annealing process.
  • QC Coronavirus Edition: Preventing Pandemics by Living on Toroidal Planets and Other Cocktail Napkin Ideas – here we present the concept of “scale-specific network geometry” as a possible tool to create bottlenecks for the exponential growth of a pandemic in a social network. That said, scale-specific geometry may also be used in populations of neurons in order to prevent specific types of synchronous behavior. This seems like a very fertile area of research.

5-MeO-DMT Awakenings: From Naïve Realism to Symmetrical Enlightenment

In the following video Leo Gura from actualized.org talks about his 30-day 5-MeO-DMT streak experiment. In this post I’ll highlight some of the notable things he said and comment along the way using a QRI-lens to interpret his experiences (if you would rather make up your mind about what he says without my commentary just go and watch the video on your own before reading what I have to say about it).

TL;DR: Many of the core QRI paradigms such as Neural Annealing, the Symmetry Theory of Valence, the Tyranny of the Intentional Object, and Hyperbolic Geometry on Psychedelics have a surprising degree of explanatory power when it comes to making sense of the peculiar process that ensues when someone takes a lot of 5-MeO-DMT. The deep connections between symmetry, valence, smooth geometry, and information content are made clear in this context due to the extreme and purified nature of the states induced by the drug.


Introduction

Recently Adeptus Psychonautica (who has interviewed me in the past about the hyperbolic geometry of DMT experiences) put out a video titled “When you have taken too much – Actualized.org“. This video caught my attention because Leo Gura did something that is rather taboo in spiritual communities, and for good reasons. Namely, he tried to convince the viewers that he had achieved a level of awakening that nobody (or perhaps only a few people) on the entire planet had ever reached. He then said he was going to isolate for a month to integrate these profound awakenings and come back with a description of what they are all about.

Thankfully I didn’t have to wait a month to satisfy my curiosity and see what happened after his period of isolation because by the time I found about it he had already posted his post-retreat video. Well, it turns out that he used those 30 days of isolation to conduct a very hard-core psychedelic experiment. Namely, he took high doses of 5-MeO-DMT daily for the entire month. I’ve never heard of anyone doing this before.

Learning about what he experienced during that month is of special interest to me for many reasons. In particular, thanks to previous research about extreme bliss and suffering, we had determined that 5-MeO-DMT is currently the psychedelic drug that has the most powerful and intense effects on valence. Recall Logarithmic Scales of Pleasure and Pain (video): many lines of evidence point to the fact that extreme states of consciousness are surprisingly powerful in ways that are completely counterintuitive. So when Leo says that there are “many levels of awakening” and goes on to discuss how each level is unrecognizably more intense and deeper than the previous one, I am very much inclined to believe he is trying to convey a true property of his experiences. Note that Leo did not only indulge in psychedelics; we are talking about 5-MeO-DMT in particular, which is the thermonuclear bomb version of a psychoactive drug (as with Plutonium, this stuff is best handled with caution). More so, thankfully Leo is very eloquent, which is rare among people who have had many extreme experiences. So I was very eager to hear what he had to say.

While I can very easily believe his trip reports when it comes to their profundity, intensity, and extraordinary degree of consciousness, I do not particularly find his interpretations of these experiences convincing. As I go about describing his video, I will point out ways in which you can take as veridical his phenomenological descriptions without at the same time having to agree with his interpretations of them. More so, if you end up exploring these varieties of altered states yourself, by reading this you will now at least have two different and competing frameworks to explain your experiences. This, I think, is an improvement. Right now the psychedelic and scientific community has very few lenses with which to interpret something as extraordinary as 5-MeO-DMT experiences. And I believe this comes at a great cost to people’s sanity and epistemic rationality.

What Are Leo’s Background Assumptions?

In the pre-retreat video Leo says that his core teachings (and what he attempts to realize on his own self) are: (1) you are literally God, (2) there is nothing but consciousness – God is infinite consciousness, (3) everything is states of consciousness – everything at all times is a different state of consciousness, (4) you are love – and love is absolute – this is all constructed out of love – fear is just fear of aspects of yourself you have disconnected from, (5) you have no beginning and no end, (6) you should be radically open-minded. Then he also adds that physical and mental health issues are just manifestations of your resistance to realizing that you are God.

What Are My Background Assumptions?

Personal Identity

I am quite sympathetic to the idea of oneness, which is also talked about with terms like nonduality and monopsychism. In philosophical terminology, which I find to be more precise and rigorous, this concept goes by the name of Open Individualism – the belief that we are all one single consciousness. I have written extensively about Open Individualism in the past (e.g. 1, 2, 3), but I would like to point out that the arguments I’ve presented in favor of this view are not based on direct experience, but rather, on logical consistency from background assumptions we take for granted. For instance, if you assume that you are the same subject of experience you were a second ago, it follows that you can exist in two points in space-time and still be the same being. Your physical configuration is different than a few seconds ago (let alone a decade), you have slightly different memories, the neurons active are different, etc. For every property you point out as your “identity carrier” I can find a counter-example where such carrier changes a little while you still remain the same subject of experience. Add to that teleportation, fission, fusion, and gradual replacement thought experiments and you can build a framework where you can become any other arbitrary person without a loss of identity. These lines of argumentation coupled with the transitivity of identity can build the case that we are indeed all one to begin with.

But realize that rather than saying that you can grasp this (potential) truth directly from first person experience, I build from agreed upon assumptions to arrive at an otherwise outlandish view. Understanding the argument does not entail “feeling we are all one”, and neither does feeling we are all one entails understanding the arguments!

Indirect Realism About Perception

There is a mind-independent world out there and you never get to experience it directly. In some sense, we each live in a private skull-bound world-simulation that tracks the fitness-relevant features of our environment. Hence, during meditation, dreaming, or psychedelic states you are not accessing any sort of external reality directly, but rather, exploring possible configurations and qualities of your inner world-simulation. This is something that Leo may implicitly not realize. In particular, interpreting 5-MeO-DMT experiences through direct realism (also called naïve realism – the view that you experience the world directly through your senses) would make you think that you are literally merging with the entire cosmos on the drug. Whereas interpreting those experiences with indirect realism merely entails that your inner boundaries are dissolving. In other words, the partitions inside your world-simulation are what implements the feeling of the self-other duality. And since 5-MeO-DMT dissolves inner boundaries, it feels as though you are becoming one with your surroundings (and the rest of reality).

Physicalism and Panpsychism

An important background assumption is that the laws of physics accurately describe the behavior of the universe. This is distinct from materialism, which would also posit that all matter is inherently insentient. Physicalism merely says that the laws of physics describe the behavior of the physical, but leaves its intrinsic nature as an open question. Together with panpsychism, however, physicalism entails that what the laws of physics are describing is the behavior of consciousness.

Tyranny of the Intentional Object

We tend to believe that what makes us happy is external to us, while in reality happiness is a state of consciousness triggered by external circumstances. Our minds lead us to believe otherwise for evolutionary reasons.

Valence Structuralism

What makes an experience feel good or bad is not its semantic content, its computational use, or even whether the experience is self-reinforcing or not. What makes experiences feel good or bad is their structure. In particular, a very promising idea that will come up below is that highly symmetrical states of consciousness are inherently blissful, such as those we can access during orgasm, meditation, psychedelics, or even just good food and a hug. Recall that 5-MeO-DMT dissolves internal boundaries, and this is indicative of increased inner symmetry (where the boundaries themselves entail symmetry breaking operations). Thus, an exotic state of oneness is blissful not because you are merging with God, but “merely” because it has a higher degree of symmetry and therefore it’s valence is higher than what we can normally experience. In particular, the symmetry I’m talking abut here may be an objective feature of experiences perhaps even measurable with today’s neuroimaging technology.

There are additional key background philosophical assumptions, but the above are enough to get us started analyzing Leo’s 5-MeO-DMT journey from a different angle.


The Video

[Video descriptions are in italics whereas my commentary is bolded.]

For the first 8 minutes or so Leo explains that people do not really know that there are many levels of enlightenment. He starts out strong by claiming that he has reached levels of enlightenment that nobody (or perhaps just a few people) have ever reached. More so, while he agrees with the teachings of meditation masters of the past, he questions the levels of awakening that they had actually reached. It takes one to know one, and he claims that he’s seen things far beyond what previous teachers have talked about. More so, he argues that people simply have no way of knowing how enlightened their teachers are. People just trust books, gurus, teachers, religious leaders, etc. about whether they are “fully” enlightened, but how could they know for sure without reaching their level, and then surpassing them? He wraps up this part of the video by saying that the only viable path is to go all the way by yourself – to dismiss all the teachers, all the books, and all the instructions and see how far you can go on your own when genuinely pursuing truth by yourself.

With this epistemological caveat out of the way, Leo goes on to describe his methodology. Namely, he embarked on a quest of taking 5-MeO-DMT at increasing doses every day for 30 days in a row.leo_10_05

At 10:05 he says that within a week of this protocol he started reaching levels of awakening so elevated that he realized he had already surpassed every single spiritual teacher that he had ever heard of. He started writing a manifesto explaining this, claiming that even the most enlightened humans are not truly as awake as he became during that week. That it had became “completely transparent that most people who say they are awake or teach awakening are not even 1% awake”. But he decided not to go forward with the manifesto because he still values the teachings of spiritual leaders, whom according to him are doing a great service to mankind. He didn’t want to start, what he called, a “nonduality war” (which is of course a fascinating term if you think about it).

The main thing I’d like to comment here is that Leo is never entirely clear about what makes an “awakening experience” authentic. From what I gather (and from what comes next in the video) we can infer that the leading criteria consists of a fuzzy blend of experience of certainty, feeling of unity, and sense of direct knowing coupled together. To the extent that 5-MeO-DMT does all of these things to an extraordinary degree, we can take Leo on his words that he indeed experienced states of consciousness that feel like awakening that are most likely inaccessible to everyone who hasn’t gone through a protocol like his. What is still unclear is how exactly the semantic contents of these experiences are verified by means other than intuition. We will come back to that.

At 16:00 he makes the distinction between awakening as merely “cessation”, “nothingness”, “emptiness”, “the Self”, or that “you are nothing and everything” versus what he has been experiencing. He agrees that those are true and worthy realizations, but he claims that before his experiences, these understandings were still only realized at a very “low level”. Other masters, he claims, may care about ending suffering, about peace, about emptiness, and so on. But that nobody seems to truly care about understanding reality (because otherwise they would be doing what he’s doing). He rebukes possible critics (arguably of the Zen variety) who would say that “understanding is a function of the mind” so the goal shouldn’t be to understand. He asserts that no, based on his lived experience, that consciousness is capable of “infinite understanding”.

Notwithstanding the challenges posed by ultrafinitism, I am also inclined to believe Leo that he has experienced completely new varieties of “understanding”. In my model of the mind, understanding something means to have the ability to render it in your world-simulation in a particular kind of way that allows you to see it from every possible angle you have access to. On 5-MeO-DMT, as we will see to a greater extent below, a certain new set of projective operations get unlocked that allow you to render information from many, many more points of view at the same time. It is unclear whether this is possible with meditation alone (in personal communication, Daniel Ingram said yes) but it is certainly extraordinarily rare for even advanced meditators to be able to do this. So I am with Leo when it comes to describing “new kinds of understandings”. But perhaps I am not on board when it comes to claiming that the content of such understandings is an accurate rendering of the structure of reality.

At 18:30 Leo asserts that what happened to him is that over the course of the first week of his experiment he “completely understood reality, completely understood what God is”. God has no beginning and no end. He explains that normal human understanding sees situations from a single point of view (such as from the past to the future). But that actual infinite reality is from all sides at once: “When you are in full God consciousness, you look around the room, and you can see it from every single point of view, from an infinite number of angle and perspectives. You see that every part of the room generates and manufactures and creates every other part. […] Here when you are in God consciousness, you see it from every single possible dimension and angle. It’s not happening lilnearly, it’s all in the present now. And you can see it from every angle almost as though, if you take a watermelon and you do a cross-section with a giant knife, through that watermelon, and you keep doing cross-section, cross-section, cross-section in various different angles, eventually you’ll slice it up into an infinite number of perspectives. And then you’ll understand the entire watermelon as a sort of a whole. Whereas usually as humans what we do is we slice down that watermelon just right down the middle. And we just see that one cross-section.”

Now, this is extremely interesting. But first, it’s important to point out that here Leo might implicitly be reasoning about his experience through the lens of direct realism about perception. That is, that as he experiences this profound sense of understanding that encompasses every possible angle at once, he seems to believe that this is an understanding of his environment, of his future and past, and of reality as a whole. On the other hand, if you start out assuming indirect realism about perception, how you interpret this experience would be in terms of the instantiation of new exotic geometries of your own world-simulation. Here I must bring up the analysis of “regular” DMT (i.e. n,n-DMT) experiences through the lens of hyperbolic geometry. Indeed, regular DMT elevates the energy of your consciousness, which manifests in brighter colors, fast movement, intricate and detailed patterns, and as curved phenomenal space. We know this because of numerous trip reports from people well educated in advanced mathematics who claim that the visual symmetries one can experience on DMT (at doses above 10mg) have hyperbolic curvature (cf. hyperbolic orbifolds). It is also consistent with many other phenomena one can experience on DMT (see the Eli 5 for a quick summary). But you should keep in mind that this analysis never claims that you are experiencing directly a mind-independent “hyperspace”. Rather, the analysis focuses on how DMT modifies the geometric properties of your inner world-simulation.

Hyperbolic Geometry of DMT Experiences copy 47

Energy-complexity landscape on DMT

Hyperbolic Geometry of DMT Experiences copy 38

DMT trip progression

Intriguingly, our inner world-simulations work with projective geometry. In normal circumstances our world-simulations have a consistent set of projective points at infinity – they render the modal and amodal features of our experience in projective scenes that are globally consistent. But psychedelics can give rise to this phenomenon of “point-of-view-fragmentation“, where your experience becomes a patchwork of inconsistent projective renderings. So even on “regular” DMT you can get the profound feeling of “seeing something from multiple points of view at once”. Enhanced with hyperbolic geometry, this can cause the stark impression that you can explore “hyperspace” with a kind of “ultra-understanding”.

Looking beyond “regular” DMT, 5-MeO-DMT is yet more crazy than that. You see, even on DMT you get the feeling that you are restricted in the number of points of view from which you can see something at the same time. You can see it from many more points of view than normal, but it’s still restricted. But the extreme “smoothing” of experience that 5-MeO-DMT causes makes it so that you cannot distinguish one point of view from another. So they all blend together. Not only do you experience semantic content from “multiple points of view at once” as in DMT, but you can erase distinctions between points of view so that one’s sense of knowing arises involving a totally new kind of projective effect, in which you actually feel you can see something from “every point of view at once”. It feels that you have unlocked a kind of omniscience. This already happens on other psychedelics to a lesser extent (and in meditation, and even sober life to an even lesser extent, but still there), and it is a consequence of smoothing the geometry of your experience to such an extent that there are no symmetry-breaking imperfections “with which to orient a projective point”. I suspect that the higher “formless” jhanas of “boundless space” and “boundless consciousness” are hitting at this effect. And on 5-MeO-DMT this effect is pronounced. More so, because of the connection between symmetry and smoothness of space (cf. Geometry Through the Eyes of Felix Klein) when this happens you will also automatically be instantiating a high-dimensional group. And according to the Symmetry Theory of Valence, this ought to be extraordinarily blissful. And indeed it is.

This is, perhaps, partly what is going on in the experience that Leo is describing. Again, I am inclined to believe his description, but happy to dismiss his naïve interpretation.

indras_net

Indra’s Net

At 23:15 Leo describes how from his 5-MeO-DMT point of view he realized what “consciousness truly is”. And that is an “infinitely interconnected self-communicating field”. In normal everyday states of consciousness the different parts of your experience are “connected” but not “communicating.” But on 5-MeO, “as you become more conscious, what happens is that every point in space inter-connects with itself and starts to communicate with itself. This is a really profound, shocking, mystical experience. And it keeps getting cranked up more and more and more. You can call it omniscience, or telepathy. And it’s like the universal communication system gets turned on for the first time. Right now your conscious field is not in infinite communication with itself. It’s fragmented and divided. Such that you think I’m over here, you are over there, my computer is over here, your computer is over there…”. He explains that if we were to realize we are all one, we would then instantly be able to communicate between each other.

Here again we get extremely different interpretations of the phenomena Leo describes depending on whether you believe in direct or indirect realism about perception. As Leo implicitly assumes direct realism about perception, he interprets this effect as literally switching on an “universal communication system” between every points in reality, whereas the indirect realist interpretation would be that you have somehow interlocked the pieces of your conscious experience in such a way that they now act as an interconnected whole. This is something that indeed has been reported before, and at QRI we call this effect “network integration“. A simple way of encapsulating this phenomenon would be by saying that the cross-frequency coupling of your nervous system is massively increased so that there is seamless information and energy transfer between vibrations at different scales (to a much lesser extent MDMA also does this, but 5-MeO-DMT is the most powerful “integration aid” we know of). This sounds crazy but it really isn’t. After all, your nervous system is a network of oscillators. It stands to reason that you can change how they interact with one another by fine-tuning their connections and get as a result decoupling of vibrations (e.g. SSRIs), or coupling only between vibrations of a specific frequency (e.g. stimulants and depressants), or more coupling in general (e.g. psychedelics). In particular, 5-MeO-DMT does seem to cause a massively effective kind of fractal coupling, where every vibration can get in tune with every other vibration. And recall, since a lot of our inner world simulation is about representing “external reality”, this effect can give rise to the feeling that you can now instantly communicate with other parts of reality as a whole. This, from my point of view, is merely misinterpreting the experience by imagining that you have direct access to your surroundings.

At 34:52 Leo explains that you just need 5-MeO-DMT to experience these awakenings. And yet, he also claims that everything in reality is imaginary. It is all something that you, as God, are imagining because “you need a story to deny that you are infinite consciousness.” Even though the neurotransmitters are imaginary, you still need to modify them in order to have this experience: “I’m talking about superhuman levels of consciousness. These are not levels of consciousness that you can access sober. You need to literally upgrade the neurotransmitters in your imaginary brain. And yes, your brain is still imaginary, and those neurotransmitters are imaginary. But you still need to upgrade them nevertheless in order to access some of the things I say.”

Needless to say, it’s bizarre that you would need imaginary neurotransmitter-mimicking molecules in your brain in order to realize that all of reality is your own imagination. When you dream, do you need to find a specific drug inside your dream in order to wake up from the dream? Perhaps this view can indeed be steel-manned, but the odds seem stacked against it.

At 38:30 he starts talking about his pornography collection. He assembles nude images of women, not only to relieve horniness, but also as a kind of pursuit of aesthetics. Pictures of nude super-models are some of the most beautiful things a (straight) man can see. He brings this up in order to talk about how he then at some point started exploring watching these pictures on 5-MeO-DMT. Recollecting this brings him to tears because of how beautiful the experiences were. He states “you’ve never really seen porn until you’ve seen it on 5-MeO-DMT.” He claims that he started to feel that this way he really felt that it is you (God) that is beautiful, which is manifested through those pictures.

A robust finding in the psychology of sexual attraction is that symmetry in faces is correlated with attractiveness. Indeed, more regular faces tend to be perceived as more beautiful. Amazingly, you can play with this effect by decorating someone’s face with face-paint. The more symmetrical the pattern, the more beautiful the face looks (and vice-versa). Arguably, the effect Leo is describing where people who are already beautiful become unbelievably pretty on 5-MeO-DMT involves embedding high-dimensional symmetries into the way you render them in your world-simulation. A lesser, and perhaps more reliable, version of this effect happens when you look at people on MDMA. They look way more attractive than what they look like sober.

Leo then brings up (~41:30) that he started to take 5-MeO-DMT on warm baths as well, which he reassures us is not as dangerous as it sounds (not enough water to drown if he experiences a whiteout). [It’s important to mention that people have died by taking ketamine on bath tubs; although a different drug, it is arguably still extremely dangerous to take 5-MeO-DMT alone on a bathtub; don’t do it]. He then has an incredible awakening surrendering to God consciousness in the bathtub, on 5-MeO-DMT, jerking off to beautiful women in the screen of his laptop. He gets a profound insight into the very “nature of desire”. He explains that it is very difficult to recognize the true nature of desire while on a normal level of consciousness because our desires are biased and fragmented. When “your consciousness becomes infinite” those biases dissolve, and you experience desire in its pure form. Which according to his direct experience turned out to be “desire for God, desire for myself”. And this is because you are, deep down “infinite love”. When you desire a husband, or sex, or whatever, you are really desiring God in disguise. But the problem is that since your path to God is constrained by the form you desire, your connection to God is not stable. But once you have this experience of complete understanding of what desire is, you finally get your desire fully quenched by experiencing God’s love.

This is a very deep point. It is related to what I’ve sometimes called the “most important philosophical question“, which is: is valence a spiritual phenomenon or spirituality a valence phenomenon? In other words, do we find experiences of God blissful because they have harmony and symmetry, or perhaps is it the other way around, where even the most trivial of pleasures, like drinking a good smoothy, feels good because it temporarily “gets you closer to God”? I lean towards the former, and that in fact mystical experiences are so beautiful because they are indeed extremely harmonious and resonant states of consciousness, and not because they take you closer to God. But I know very smart people who can’t decide between these views. For example, my friend Stuart Garvagh writes: 

What if the two options are indistinguishable? Suppose valence is a measure of the harmony/symmetry of the object of consciousness, and the experience of “Oneness” or Cosmic Consciousness is equivalent to having the object of consciousness be all of creation (God‘s object), a highly symmetrical, full-spectrum object (full of bliss, light, love, beingness, all-knowledge, empty of discernible content or information). All objects of consciousness are distortions (or refractions, or something) of this one object. Happiness is equivalent to reducing or “polishing-out” these distortions. Thus, what appears to be just the fact of certain states being more pleasant than others is equivalent to certain states being closer to God‘s creation as a whole. Obviously this is all pure speculation and just a story to illustrate a point, but I could see it being very tough to tease apart the truth-value of 1 and 2. Note: I’m fairly agnostic myself, but lean towards 2 (bliss is the perfume of “God realizing God” or the subject of experience knowing Itself). I would very much love to have this question answered convincingly!

At 50:00 Leo says that “everything I’ve described so far is really a prelude to the real heart of awakening, which is the discovery of love. […] I had already awakened to love a number of times, but this was deeper. By the two week mark the love really started to crack open. Infinite self-love. You are drowning on this love.” He goes on to describe how at this point he was developing a form of telepathy that allowed him to communicate with God directly (which is, of course, a way of talking to himself as he is God already). It’s just a helpful way to further develop. And what God was showing him was how to receive self-love. It was so much at first he couldn’t handle it. And so he went through a self-purification process.

An interesting lens with which to interpret this experience of purification is that of neural annealing. Each 5-MeO-DMT experience would be making Leo’s nervous system resonate in ways in new ways, slowly writing over previous patterns and entraining the characteristic high-symmetry patterns of the state. Over time, the nervous system adjusts its weights in order to be able to handle that resonance without getting its patterns over-written. In other words, Leo has been transforming his nervous system into a kind of high-valence machine, which is of course very beneficial for intrinsic feelings of wellbeing (though perhaps detrimental to one’s epistemology).

55:00: He points out that unlike addictive drugs, he actually had to push himself very hard to continue to take 5-MeO-DMT everyday for 30 days. He stopped wanting to do it. The ego didn’t want it. And yes, it was pleasurable once he surrendered on every session, but it was difficult, heavy spiritual work. He says that he could only really do this because of years of practice with and without psychedelics, intense meditation, and a lot of personal development. And because of this, he explains his 5-MeO experiences felt like “years of spiritual work condensed into a single hour.” He then says that God will never judge you, and will help you to accept whatever terrible things you’ve done. And many of his subsequent trips were centered around self-acceptance. 

Following the path of progressive neural annealing, going deeper and deeper into a state of self-acceptance can be understood as a deeper harmonization of your nervous system with itself.

At 1:01:20, Leo claims to have figured out what the purpose of reality truly is: “Reality is a contest for who can love who more. That’s really what life is about when you are fully conscious. […] Consciousness is a race for who can love who more. […] An intelligent fully conscious consciousness would only be interested in love. It wouldn’t be interested in anything else. Because everything else is inferior. […] Everything else is just utter silliness!”

I tend to agree with this, though perhaps not in an agentive way. As David Pearce says: “the pleasure-pain axis discloses the universe’s intrinsic value function.” So when you’ve annealed extremely harmonious patterns and do not get distracted by negative emotion, naturally, all there is left to do is maximize love. Unless we mess up, this is the only good final destiny for the cosmos (albeit perhaps it might take the form of a Hedonium shockwave, which at least in our current human form, sound utterly unappealing to most people).

1:06:10 “[God’s love] sparks you to also want to love it back. You see, it turns into a reciprocal reaction, where it is like two mirrors that are mirroring light between each other like a laser beam that is bouncing between two mirrors. And it’s bouncing back and forth and back and forth. And as it bounces back and forth it becomes more and more concentrated. And it strengthens. And it becomes more coherent. And so that’s what started happening. At first it started out as just a little game. Like ‘I love you, I love you, I love you’. A little game. It sounds like it’s almost like childish. And it sort of was. But then it morphed from being this childish thing, into being this serious existential business. This turned into the work. This was the true awakening. Is that with the two mirrors, you know, first it took a little while to get the two mirrors aligned. Because you know if the two mirrors are not perfectly aligned, the laser beam will kind of bounce back and forth in different directions. It’s not going to really concentrate. So that was happening at first. […] The love started bouncing back and forth between us, and getting stronger and stronger. […] Each time it bounces back to me it transforms me. It opens me up deeper. And as it opens me up deeper it reveals blockages and obstacles to my capacity to love.”

Now this is a fascinating account. And while Leo interprets it in a completely mystical way, the description also fits very well an annealing process where the nervous system gets more and more fine-tuned in order to be able to contain high levels of coherent energy via symmetry. Again, this would be extremely high-valence as a consequence of the Symmetry Theory of Valence. Notice that we’ve talked about this phenomenon of “infinite mirrors” on psychedelics since 2016 (see: Algorithmic Reduction of Psychedelic States).

At ~1:09:30 he starts discussing that at this point he was confronted by God about whether he was willing to love the holocaust, and rape, and murder, and bullies, and people of all sorts, even devil worshipers. 

Two important points here. First, it is a bit ambiguous whether Leo here is using the word “love” in the sense of “enjoyment” or in the sense of “loving-kindness and compassion”. The former would be disturbing while the latter would be admirable. I suppose he was talking about the latter, in which case “loving rape” would refer to “being able to accept and forgive those who rape” which indeed sounds very Godly. This radical move is explored in metta (loving-kindness) meditation and it seems healthy on the whole. And second: Why? Why go through the trouble of embracing all the evil and repulsive aspects of ourselves? One interpretation here, coming back to the analysis based on neural annealing, is that any little kink or imperfection caused by negative emotion in our nervous system will create slight symmetry breaking effects on the resonance of the entire system as whole. So after you’ve “polished and aligned the mirrors for long enough” the tiny imperfections become the next natural blockage to overcome in order to maximize the preservation of coherent energy via symmetry.

~1:12:00 Leo explains that the hardest thing to love is your own self-hatred. In the bouncing off of the love between you and God, with each bounce, you find that the parts you hate about yourself reflect an imperfect love. But God loves all of you including your self-hatred. So he pings you about that. And once you can accept it, that’s what truly changes you. “Because when you feel that love, and you feel how accepting it is, and how forgiving it is of all of your evil and of all of your sins… that’s the thing that kills you, that transforms you. That’s what breaks your heart, wide open. That’s what gets you to surrender. That’s what humbles you. That’s what heals you.” Leo then explains that he discovered what “healing is”. And it is “truth and love”. That in order to heal anyone, you need to love them and accept them. Not via sappy postcards and white lies but by truth. He also states that all physical, mental, and spiritual ailments have, at their root, lack of love.

If love is one of the cleanest expressions of high-valence symmetry and resonance, we can certainly expect that inundating a nervous system with it will smooth and clean its blockages, i.e. the sources of neural dissonance. Hence the incredible power of MDMA on healing nervous systems in the short-term. Indeed, positive emotion is itself healing and enhances neural coherence. But where I think this view is incomplete is in diagnosing the terrible suffering that goes on in the world in terms of a lack of love. For instance, are cluster headaches really just the result of lack of self-love? In here must bring back the background assumption of physicalism and make a firm statement that if we fall into illusion about the nature of reality we risk not saving people (and sentient beings more generally) who are really in the depth of Hell. Just loving them without taking the causally-relevant physical action to prevent their suffering is, in my opinion, not true love. Hence the importance of maintaining a high level of epistemic rigor: for the sake of others. (See: Hell Must Be Destroyed).

1:22:30 Leo explains that in this “love contest” with God of bouncing off love through parallel mirrors the love became so deep that for the first time in his life he felt the need to apologize: “I’m sorry for not loving more.” He goes into a sermon about how we are petty, and selfish, etc. and how God loves us anyway. “Real love means: I really love you as you are. And I don’t need anything from you. And especially all those things that you think I want you to change about you, I don’t need you to change. I can accept them all exactly as they are. Because that’s love. And when you realize THAT, that’s what transforms you. It is not that God says that he loves you. He is demonstrating it. It’s the demonstration that transforms you.” Leo expresses that he was then for the first time in his life able to say “thank you” sincerely. Specifically, “thank you for your love”: “This is the point at which you’ve really been touched by God’s love. And at this point you realize that that’s it, that’s the point, that’s the lesson in life. That’s my only job. It’s to love.” And finally, that for the first time in his life he was able to say “I love you” and truly mean it. “And you fall in love with God… but it doesn’t end there.”

An interesting interpretation of the felt-sense of “truly meaning” words like “I’m sorry”, “thank you”, and “I love you” is that at this point Leo has really deeply annealed his nervous system into a vessel for coherent energy. In other words, at this point he is saying and meaning those words through the whole of his nervous system, rather than them coming from a fragmented region of a complex set of competing internal family systems in a scattered way. Which is, of course, the way it usually goes.

1:35:30 Leo explains that at this point he started going into the stage of being able to radiate love. That he was unable to radiate love before. “I love that you are not capable of love. I love that. And when that hits you, that’s what fills you with enough love to overcome your resistance to love that next level thing that you couldn’t love.” Then at ~ 1:38:00 it gets really serious. Leo explains that so far he was just loving and accepting past events and people. But he was then asked by God whether he would be willing to live through the worst things that have happened and will happen. To incarnate and be tortured, among many other horrible things. And that’s what true love really means. “When you see a murder on the TV, you have to realize that God lived through that. And the only reason he lived through that is because it loved it.”

I do not understand this. Here is where the distinction between the two kinds of senses of the word “love” become very important. I worry that Leo has annealed to the version of love with the meaning of “enjoyment” rather than “loving-kindness and compassion”. Because a loving God would be happy to take the place of someone who went through Hell. But would a loving God send himself to Hell if nobody had to in the first place? That would just create suffering out of nothing. So I am confused about why Leo would believe this to be the case. It’s quite possible that there are many maxima of symmetry in the nervous system you can achieve with 5-MeO-DMT, and some of them are loving in the sense of compassionate and others are crazy and would be willing to create suffering out of nothing from a misguided understanding of what love is supposed to be. Again, handle Plutonium with caution.

1:43:00 Leo started wondering “what is reality then?” And the answer was: “It’s infinite consciousness. Infinite formless consciousness. So what happens was that my mind in my visual field as I was in that bathtub. My mind and my visual field focused in on empty space, and I sort of zoomed into that empty space and realized that that empty space is just love”. He then describes a process where his consciousness became more and more concentrated and absorbed into space, each dot of consciousness branching out into more and more dots of consciousness, turning into the brightest possible white light. But when he inquired into what was that white light he kept seeing that there was no end to it, and rather, that each point was always connected to more points. Inquiring further, he would get the response that at the core, reality is pure love. That it wouldn’t be and couldn’t be any other way.

The description sounds remarkably close to the formless jhanas such as “boundless space” and “boundless consciousness”. The description itself is extremely reminiscent of an annealing process, reaching a highly energized state of consciousness nearly devoid of information content and nearly perfectly symmetrical. The fact that at this incredibly annealed level he felt so much love supports the Symmetry Theory of Valence.

147:28 – And after Leo realizes that “Of course it is love!” he says that’s when the fear comes: “Because then what you realize is that this is the end. This is the end of your life. You are dead. If you go any further you are dead. Everything will disappear. Your family, your friends, you parents, all of it is completely imaginary. And if you stop imagining it right now, it will all end. If you go any further into this Singularity, you will become pure, formless, infinite, love for ever, loving itself forever. And the entire universe will be destroyed as if it never existed. Complete nothingness. Complete everythingness. You will merge into everyone.”

This sounds like the transition between the 6th and 7th Jhana, i.e. between “boundless consciousness” and “nothingness”. Again, this would be the result of further loss of information via an annealing process, refining the symmetry up to that of a “point”. Interestingly, Mike Johnson in Principia Quallia points out that as symmetry approaches an asymptote of perfection you do get a higher quality of valence but at the cost of reduced consciousness. This might explain why you go from “the brightest possible love” to a feeling of nothingness at this critical transition.

1:48:25: “…You will merge into everyone. Your mother, your father, your children, your spouse, Hitler, terrorists, 9/11, Donald Trump, rape, murder, torture, everything will become pure infinite love, merging completely into itself, there will be no distinction between absolutely anything, and that will be the end. And you will realize what reality is. Infinite consciousness. Love. God. And you will realize that everything in your life from your birth to this point has just been some imaginary story. A dream that was design to lead you to pure absolute infinite love. And you will rest in that love forever. Forever falling in love with yourself. Forever making love to yourself. Forever in infinite union. With every possible object that could ever exist. Pure absolute, omnipotent, omniscient, perfect, intelligent, consciousness. Everything that could ever possibly be, is you. And THAT is awakening. When you are this awake, you are dead. And you have no desire for life. There is no physical existence. There is no universe. Nothing remains. Your parents, and your spouse, and your children, they don’t stay back and keep living their lives, enjoying their life without you while your body drops dead. No, no, no, no, no. This is much more serious than that. If you do this. If you become infinite love, you will take everybody with you. There will not be anybody left. You will destroy the entire universe. Every single sentient being will become you. They will have no existence whatsoever. Zero. They will die with you. They will all awaken with you. It’s infinite awakening. It’s completely absolute. There will not be anything left. You will take the entire universe with you. Into pure oneness. THAT’S awakening.”

This is not the first time I hear about this kind of experience. It certainly sounds extraordinarily scary. Though perhaps a negative utilitarian would find it to be the ultimate relief and the best of all possible imaginable outcomes. With the human survival instinct, and quite possibly a body fully aroused with the incredible power of 5-MeO-DMT, this is bound to be one of the most terrifying feelings possible. It’s quite likely that it may be one element of what makes “bad 5-MeO-DMT experiences” so terrifying. But here we must recall that the map is not the territory. And while an annealing process might slowly write over every single facet of one’s model of reality and in turn making them part of a super-cluster of high-dimensional resonance that reflects itself seemingly infinitely, doing this does not entail that you are in fact about to destroy the universe. Though, admittedly, it will surely feel that way. Additionally, I would gather that were it possible to actually end the universe this way, somebody, somewhere, in some reality or another, would have already done so. Remember that if God could be killed, it’d be dead already.

1:52:01: “And I didn’t go there! As you can tell, since I’m still sitting here. I’m not there. I was too afraid to go there. And God was fine with it. It didn’t push me. But that’s not the end of the story! It’s still just the beginning.” He then goes on to explain that a part of him wanted to do it and another part of him didn’t want to. He says it got really loopy and weird; this really shook him. That God was beckoning him to go and be one forever, but he was still ambivalent and needed some time to think about it. He knew it would make no difference, but he still decided to ‘make preparations’ and tell his family and friends that he loves them before moving forward with a final decision to annihilate the universe. By the time he had done that… he had stopped taking 5-MeO-DMT: “The experiences had gotten so profound and so deep… this was roughly the 25th or 27th day of this whole 30 day process. I swore off 5-MeO-DMT and said ‘Ok I’m not doing any more of this shit. It’s enough'”. He explains that by this time the drug was making him feel infinite consciousness when waking up (from sleep) the next day. He felt the Singularity was sucking him into it. It felt both terrifying and irresistible. Every time he would go to sleep it would suck him in really strongly, and he kept resisting it. He would wake up sweaty and in a panic. He was tripping deeper in his sleep than in the bathtub. He couldn’t sleep without this happening, and it kept happening for about 5 days. “I just want to get back to normal. This is getting freaky now.” 

I’ve heard this from more than a couple people. That is, that when one does 5-MeO-DMT enough times, and especially within a short enough period of time, the “realizations” start to also happen during sleep in an involuntarily way. One can interpret this as the annealing process of 5-MeO-DMT now latching on to sleep (itself a natural annealing process meant to lessen the technical debt of the nervous system). Even just a couple strong trips can really change what sleep feels like for many days. I can’t imagine just how intense it must have been for Leo after 25 days straight of using this drug.

2:01:40 – Leo explains that when he was dozing off with a blanket on his living room (terrified of sleeping on his bed due to the effect just described) he experienced a “yet deeper awakening” which involved realizing that all of his previous awakenings were just like points and that the new one was like a line connecting many points. “Everything I’ve said up to this point were just a single dimension of awakening. And then what I broke through to is a second dimension. A second dimension of awakening opened up. This second dimension is completely unimaginable, completely indescribable, cannot be talked about, cannot be thought about. And yet it’s there. In it, are things that are completely outside of the physical universe that you cannot conceive or imagine.” He goes on to explain that there are then also a third, fourth, fifth, etc. dimensions. And that he believes there is an infinite number of them. He barely even began to explore the second dimension of awakening, but he realized that it goes forever. It kept happening, he had intense emotional distress and mood swings. But gradually after five more days it subsided, and he started to be able to sleep more normally. “And I’ve been working to make sense of all of this for the last couple of weeks. So that’s what happened.”

Alright, this is out of my depth and I do not have an interpretation of what this “second dimension of awakening” is about. If anyone has any clue, please leave a comment or shoot me an email. I’m as as confused as Leo is about this.

~2:05:00 – Leo confesses he does not know what would happen if he went through with joining the Singularity and mentions that it sounds a bit like Mahasamādhi. He simply has not answers at this point, but he asserts that the experience has made him question the extent of the enlightenment of other teachers. It also has made him more loving. But still, he feels frustration: “I don’t know what to do from here.”

And neither do I. Do you, dear reader?

Postscript: In the last 10 minutes of the video Leo shares a heart warming message about how reality is, deep down, truly, “just love” and that him saying this may be a seed that will blossom into you finding this out for yourself at some point in the future. He ends by cautioning his audience to not believe as a matter of fact that this is the path for everyone. He suggests that others should just use his examples from his own journey as examples rather than an absolute guide or how-to for enlightenment. He asks his audience to make sure to question the depth of their own awakening – to not believe that they have reached the ultimate level. He admits he has no idea whether there is an ultimate level or not, and that he still has some healing to do on himself. He remains dissatisfied with his understanding of reality.


Thank you for reading!

THE END

Making Amazing Recreational Drug Cocktails

Californidine

Imagine that you were tasked with creating a molecule to represent the spirit of California. I think that I would just glue together two MDMA molecules and call it a day.

1200px-Californidine.svg

Californidine

It turns out Californidine is indeed a real molecule, named after the California Poppy. I am still wrapping my head around the fact that Californidine can be described as two MDMA molecules sharing the nitrogen atom and with the end of the carbon chain of each MDMA molecule bonded at the 2-position of the benzene ring of the other one (minus a hydrogen atom). Interestingly, this compound has no psychedelic or empathogenic action. At best, it can be described as a very mild and unreliable relaxing agent of “herbal strength” akin to the active ingredients of chamomile, valerian, or ashwagandha. So, joining two powerful heart-openers gives rise to a mild sleep-inducer? Perhaps this is a metaphor for something.

californidine_mdma_

Californidine and MDMA

But that’s not what I want to talk to you about today. While gluing together psychoactive molecules may not have a (cartoonishly) desirable additive effect, doing so does express the spirit of what I want to propose today. And that is the impulse to use a creative and fun approach to drug design, letting your imagination run wild to avoid prematurely discarding one’s crazy ideas.

Notable Leads for Great Drug Combos

Over the last 10 years I’ve read many (many!) trip reports and have talked to hundreds of experienced psychonauts (see also: r/replications). It is largely thanks to a subset of these psychonauts, which for lack of a better term could be described as the subset of rational psychonauts, that I’ve been able to assemble empirically testable models for psychedelic phenomenology (some examples: Algorithmic Reduction of Psychedelic States, Hyperbolic Geometry of DMT Experiences, Quantifying Bliss, How to Secretly Communicate with People on LSD, etc.). Although my focus has largely been on the effects of individual drugs, I’ve become very cognizant of the fact that drug combinations can produce effects not accessible with individual substances. In other words, when it comes to mixing psychoactive substances, the sum is more often than not different from the sum of its parts. Some of these effects seem extremely significant both from a scientific and a philosophical point of view.

But first, an important disclaimer: mixing drugs is dangerous and you should never do it unless you really know what you are doing. The pile of celebrity deaths caused by multiple drug intoxication is only scratching the surface. Indeed, there are many combinations of drugs that are deadly even when the individual drugs taken on their own are relatively safe. For example, while 5-MeO-DMT is relatively safe when vaporized (save for egregiously negligent uses of the drug and the occasional drowning in one’s own vomit), taking 5-MeO-DMT orally in combination with an MAOI leads to extremely toxic reactions, such as severe hypertensive symptoms, overheating, and serotonin syndrome. Don’t do it. As a very rough guide for how mixtures of psychoactives behave, study the chart below.

Combo_2

Welcome to the practice of combining drugs. You may die. (source)

That said, just as drug combinations have a dangerous side, they also likely harbor hidden gems that are very safe, enjoyable, and mind-expanding in ways inaccessible via single drugs. As a general overview, some examples of the possible benefits of drug combinations include: (1) Enhanced euphoria, e.g. see speedball which is massively euphoric but also very dangerous, (2) reduced psychological discomfort (e.g. anxiolytics with psychedelics), (3) uniquely interesting effects, e.g. LSD + MDMA (see below), and (4) reduced physical side-effects and medical risks, e.g. calcium blockers to reduce MDMA neurotoxicity, 5HT2B antagonists to reduce cardiotoxicity of psychedelics, etc. as we’ll discuss. In addition, it is worth mentioning that from a therapeutic point of view, we also have the “more dakka effect“, where some conditions only respond to combining enough drugs (e.g. oncology). It’s possible chronic pain or severe depression may legitimately require multiple drugs to be adequately dealt with. Now let us examine in more detail some particularly interesting categories of drug combinations:

Psychedelics + Anxiolytics: According to many reports, phenibut in small doses seems to significantly reduce the anxiety that comes up on psychedelics. I am ambivalent about sharing this information given the fact that phenibut can become a huge problem for some people, but I think that on the whole it is wise for people to know that an over-the-counter “nootropic” can actually help avoid fear, discomfort, and panic attacks during a psychedelic experience.

Cannabis + Psychedelics: I generally find two kinds of psychedelic drug users. Those who cannot think of having a psychedelic trip without at some point smoking a joint, vaping, or eating a cannabis edible. And then those who would never dare to combine the two because they once had a terrifying experience with the combo. Interestingly, some of the people I’ve met over the years who seem to be able to easily handle massive doses of psychedelics (e.g. 500 micrograms of acid) respond terribly to weed, and especially badly if they are already tripping. Cannabis both modifies and potentiates psychedelic states of mind. It has a tendency to make the experience more conceptual rather than sensory or mystical. The combination also greatly increases the probability of getting stuck in time loops.

Empathogens + Psychedelics: One of the best descriptions of MDMA + LSD (also called candy-flipping) that I’ve found comes from Steven Lehar (emphasis added):

Under LSD and ecstasy I could see the flickering blur of visual generation most clearly. And I saw peculiar ornamental artifacts on all perceived objects, like a Fourier representation with the higher harmonics chopped off. LSD by itself creates sharply detailed ornamental artifactslike a transparent overlay of an ornamental lattice or filigree pattern superimposed on the visual scene, especially in darkness. Ecstasy smooths out those sharp edges and blurs them into a creamy smooth rolling experience. I would sometimes feel some part of my world suddenly bulging out to greater magnification, like a fish-eye lens distortion appearing randomly in space, stretching everything in that portion of space like a reflection in a funhouse mirror.

– Steven Lehar (The Phenomenal Character of LSD + MDMA)

Not everyone responds well to this combination, and given the nature of these substances, it seems likely that the dosages and the relative timing have a large influence on how the experience develops. I’ve heard three relatively “established” ways in which people use this combination. First, you have the school that says that you should take the MDMA at or slightly after the peak of the effects of LSD, that is 4-4:30h after taking it. The reasoning here is that you don’t want to be caught coming down from the MDMA while still having a long time to go on LSD since the acid could enhance the feelings of the comedown. The delayed gratification also pays-off by giving you several hours to face the problems you want to solve unaided and see how far you can get before the mood boost of MDMA gives you the determination to be contented with it.

The second school of thought about candy-flipping says that the biggest factor in how psychedelic experiences turn out is how they start. So what you want to do is take the MDMA 1 to 1:30 hours before the acid. This way, you only embark upon the inner journey when you are already in a really, really good chill state of mind. Some people report that the acid picks up the empathogenic quality of the state, amplifies it, and carries it on for much longer than if you had only taken MDMA alone.

There are many proponents and detractors to both of these schools. What I’ve seen more or less everyone agree on is to avoid taking substantial doses of LSD and MDMA (e.g. 200micrograms LSD + 120mg MDMA) at the same time. Apparently this is simply just too overwhelming and synergistic to be enjoyable, often causing a lot of nausea and palpitations.

The third school, however, is to take only a small dose of both at the same time. Say, 35micrograms LSD and 35mg MDMA. This apparently is an extremely positive combination. The experience is not mild due to the synergy, and it seems to provide an open, creative, level-headed mindset for many hours without much of a comedown or hangover. As with everything here, your mileage may vary.

Psychedelics + Dissociatives: Psychedelics and dissociatives have profound non-linear mixing effects. According to multiple sources, the right combination of LSD, Ketamine, and THC can give rise to a “free-wheeling hallucination“. This is a state of consciousness in which you gain a great degree of conscious control over the contents of the hallucinated world, so that you can project your will by saying “let there be a chair in front of me” and you will see it manifest in exquisite detail. You can rotate, translate, invert, fibrate, and project the chair in any way you want, as if you were now able to use your brain as a very general game engine of consciousness. That said, even when this doesn’t happen, the combination of psychedelics and dissociatives is ridiculously synergistic. People report getting stuck in extremely energetic time-loops akin to those caused by psychedelics and cannabis, but more powerful (cf. trip report of DMT + nitrous oxide). Steven Lehar calls the effect where the presence of a psychedelic changes the quality of a dissociative as “dissociative coloring”. I’ve been amazed at the fact that there is no mistaking when someone has previously experienced LSD and nitrous together. You don’t get reactions like “it didn’t do much for me”. This combo usually has a special place in the memory of a person who has experienced it. Eyes brighten, curiosity sparks. I’ve been asked on multiple occasions “what do you think is going on with the strange synergy between LSD and nitrous?” Now, 5-MeO-DMT and DMT are very different, and the LSD + nitrous state seems to have some resemblance with the 5-MeO-DMT state. They share that strange feeling of becoming a kind of saturated resonance box. The feeling is one of becoming a vessel full of coordinated and coherent vibrations that unearth and dissolve internal boundaries and blockages. The process inherently blocks your ability to conceptualize in a dualistic way. The cognitive content of the state is better captured by a huge blinking sign that reads “THIS, THIS, THIS” on repeat rather than the more usual “that thing over there connected to this over here, modulated by what happens there” kind of cognitive state we are more familiar with. DMT on its own is very different than this, in that the mental formations and patterns of binding that emerge are extremely specific, detailed, and irreducibly complex. Not so on the upper ranges of the dissociative and psychedelic cocktail, where the resonance is profound and the asymmetries needed to store complex information are constantly smoothed out by the ongoing full-body bath of reverb. (cf. Neural Annealing).

Dissociatives + Empathogens: According to several trip reports and credible personal communications, taking ketamine while on MDMA can bring back “the magic” that one only ever experienced with MDMA the first few times using it. Also MDMA and nitrous have profound research-worthy synergy.

Potentiation: Shulgin reported that substances that don’t feel psychedelically active on their own may nonetheless potentiate the effects of other psychedelics. For instance:

(with 160 mg of MDPR followed at 2h by 100μg LSD) This proved to be almost too intoxicating, and a problem arose that had to have a solution. The entire research group was here, and all were following this same regimen. Two hours into the second half of the experiment a telephone call came that reminded me of a promise I had made to perform in a social afternoon with the viola in a string quartet. Why did I answer the phone? My entire experience was, over the course of about 20 minutes, pushed down to a fragile threshold, and I drove about 10 minutes to attend a swank afternoon event and played an early Beethoven and a middle Mozart with an untouched glass of expensive Merlot in front of me. I could always blame the booze. I declined the magnificent food spread, split, and returned to my own party. Safely home, and given 20 more minutes, I was back into a rolling +++ and I now know that the mind has a remarkable ability to control the particular place the psyche is in. 

(Entry on MDPR, from PIHKAL)

More common than the above, ayahuasca is intrinsically a drug combo primarily of the potentiation kind. As mentioned before, cannabis not only alters but also potentiates the effects of psychedelics. It is worth mentioning there is a community of people who believe that noopept (a cholinergic nootropic, see below) can potentiate MDMA. While there is some evidence that MDMA is itself mildly cholinergic– and thus provides a sense of mental clarity in addition to the loved-up feeling- too much cholinergic action tends to make people feel rigid, robotic, and hyper-cerebral. I am therefore personally skeptical of the benefits of combining something like noopept with MDMA, as the potentiation of some of its qualities may come at the cost of reduced emotional sensitivity. Why trade a feeling of renewed innocence and receptivity with calculating prowess? I doubt this is the best use of a roll.

Anti-tolerance Drugs: This is a category of combinations with tremendous potential to relieve suffering, to the extent that I think of it as a humanitarian tragedy that there are no concerted research efforts currently in this direction. Sufferers of chronic pain and treatment-resistance depression could make use of drugs that help them keep the tolerance to the drugs they depend upon for having a livable life under control. I know this has a lot of the ring of turtles all the way down (“when are you going to get the anti-tolerance drugs for anti-tolerance drugs? And then the anti-tolerance for anti-tolerance for…”) but I am sincere when I say that looking here may pay off in spades. Already we see ibogaine doing other-worldly magnificent things to cure addiction and reverse tolerance. Who knows what a large targeted research program with this focus may discover. Some examples of anti-tolerance drugs include proglumide, ibogaine, and black seed oil for opioids, and flumazenil for benzodiazepines.

Prevent Physical Side Effects: Epidemiological data suggests that chronic or heavy use of 5HT2B agonists may lead to heart valve disease (cf. Fen-Phen), which does not bode well for the long-term (as opposed to acute) safety of many psychedelic compounds. Now, neuroscientist Thomas Ray believes that 5HT2B may be necessary for some of the characteristic psychedelic action of entheogens, so blocking it altogether may come at the cost of eliminating the reason why the drug is interesting. That said, we do know that 5-MeO-DMT is profoundly psychedelic and yet has negligible 5HT2B activity. It would be very useful to know what happens when one combines psychedelics with heavy 5HT2B affinity, like 2C-B and DOB, with 5HT2B antagonists (usually prescription medicines). Would blocking 5HT2B agonism avoid cardiotoxicity? And what would the drug feel like then? Another interesting lead is the affinity of compounds like 2C-E and 2C-T-2 to the 5HT3 receptor, which is predominantly in the gut and modulates feelings like nausea. Additionally, since 5HT3 antagonists are antiemetic it really stands to reason that taking one before e.g. tripping on shrooms may give you a much less, ahem, visceral experience. Finally, I would like to explore the implications of the fact that of all of the compounds in Ray’s study the only one with significant affinity for calcium channels is MDMA. Would this be related to its neurotoxicity? And would taking a calcium channel blocker prevent it? It might still be wise regardless simply as a way to lessen the cardiac load of the compound.

Nootropic Stacks (cf. the Qualia Pill):  Many people who explore nootropics make “stacks”. That is, rather than taking only piracetam, they might take a combination of piracetam, aniracetam, pramiracetam, coluracetam, and l-tyrosine. I suspect that this is popular because most nootropics are pretty mild and often hard to notice, and people want to be able to feel the effects. I generally do not think this is sensible, though, as we don’t understand these substances well enough. More so, branded “nootropic stacks” can have upwards of 30 different psychoactive substances crammed together in half a dozen pills you are supposed to take daily. While I do think there are likely gems to be found in the vast combinatorial space of cognition-boosting chemicals, I simply do not see any way in which the current major brands of nootropic stacks could have done the type of research needed to find them. I therefore do not personally recommend you go out and try such combos, at least not until we know a lot more about how to do combinations properly. If you want to try nootropic stacks, I’d recommend you start with small doses of two or three well-researched nootropics at most and do your own research thoroughly before settling on a particular combination.

NO-MISMATCH-PATTERN

LSD + DMT Visual Replication

Psychedelics and Psychedelics: A classic psychedelic combo that I’ve heard a lot about is LSD + DMT. The state that emerges from this combination is apparently unique, though if you take enough DMT the LSD fades into the background. Apparently psychedelics tend to have a characteristic spectral effect on your brain’s harmonics (see: Connectome-Specific Harmonic Waves on LSD), which manifests in the form of experiencing “vibes of different frequencies” specific to the drug you are taking. The case of LSD and DMT is very interesting, since their characteristic frequencies are sufficiently far apart (to put a number on it, LSD may be in the vicinity of 18Hz while DMT may be close to 30Hz) that they can be separated easily. You thus get a spectral effect of two peaks interfering with one another, oftentimes creating a powerful 3D grid of Moiré patterns, like a super-charged version of the “regular” DMT Chrysanthemum. As a method for spectral analysis, studying the beat patterns of psychedelic drug combos could go a long way in formulating a systematic characterization of their phenomenology. Speculatively, this may even allow us to come up with specific psychedelic drug cocktails that produce maximally consonant harmonious effects.

Idiosyncratic Responses

A final thought to add to this section concerns the fact that people respond differently to drugs. One can reason that if drug A affects 20% of people in a different way while drug B affects 10% of people in a different way, that A + B would lead to 4 different kinds of responses. More so, the more drugs you pile on top of each other, the more specific and individualized the response would be. I think that this is likely true in the general case, but I would argue that it is not universally true. A useful analogy here is with the way people respond to the scent of different molecules: you may lack the gene that encodes the receptor for a particular molecule, but perfumes usually have 30 or more scent-contributing molecules, so the experience of a perfume may be more similar between people than their experience of individual molecules. At the extreme, we have the phenomenon of “white noise scent” where once you mix 40+ molecules in equal (intensity-adjusted) proportions that span scent-space, it all starts smelling the same. The notion of “scent entropy” can be imported to drugs as well: I would expect a kind of inverted U-curve for “how idiosyncratic” the responses to drug combinations are as a function of the total entropy of the combo.

Drug Cocktails From First Principles

The way we aim to understand psychoactive substances at the Qualia Research Institute is in terms of the way they modify the neuroacoustic profile of the brain. And while this is what I see as the most promising approach moving forward, I believe that there is nonetheless a lot of low-hanging fruit at the receptor level of analysis.

The first time I’d thought of trying to emulate the effects of a drug using a cocktail of other drugs came up years ago when I found out that MDMA is likely neurotoxic. At the time I thought perhaps it was just a matter of getting the right dopaminergic, serotonergic, and oxytocinergic activity going for you to replicate the MDMA high. It’s a good thought, and some people have taken it to heart, such as the creators of “Poly”, an MDMA-like cocktail (cf. Kisspeptine). But as we’ll see, MDMA is more complex than that, and we may need to consider far more variables to make a “credible MDMA substitute”.

Looking beyond drug combos of only two or three drugs, and with a nod to concepts from the field of high-entropy alloys (HEAs), we could start thinking about the secret gems to be found in the vast combinatorial space of “high-entropy drug combos”. But what kind of principles could we use to safely combine 5+ drugs? The full story will probably be much, much more complicated than the following approach, but it is still nonetheless worth exploring as a first pass. Namely, to break down each drug in terms of their receptor affinity profile and then use those affinities additively to create arbitrary “synthetic” receptor affinity profiles. There are many reasons why this might not work: receptor affinity may not work linearly or have a clear rule-based behavior. For instance, it is still unclear if a single drug that has affinity for key serotonin receptors (say 5HT2A, 5HT2B, and 5HT7) in addition to working as an NMDR antagonist would produce the same feeling of “synergistic action” as there is between psychedelics and dissociatives. More so, there could be additional intra-cellular signaling specific to each molecule, so that two molecules that work as agonists with the exact same 5HT2B affinity may have different downstream effects inside the neuron, and then those intracellular effects might have phenomenological properties of their own. But leaving all of those caveats and unknowns aside for a moment, what would it look like to create drug cocktails with this method?

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True for both people and drugs!

After giving it some thought I realized that the problem can be reduced to a non-negative least squares (NNLS) optimization (non-negative because, as they say: “you can always take more drugs, but you cannot take less drugs”). It turns out there are already open source implementations of algorithms that solve this optimization problem (for both R and Python)*. So I downloaded the data from the famous Thomas Ray study of psychedelic receptor affinity and played with the data and the non-negative least squares method in a Jupyter notebook for a bit. The first thing I tried was to create a compound like 2C-B but better. Under dubious- but not entirely random- assumptions, I set the desired receptor affinity to be that of 2C-B but with the following modifications: to have the 5HT2B affinity be as low as possible in order to minimize cardiotoxicity concerns, and borrow from MDMA’s unique profile the hypothesis that the Imidazoline receptor is related to heart-opening effects. Additionally, I modified the receptor profile so that the drug would give you more focus than 2C-B by having a higher affinity for the dopamine receptors. To top it off, I racked up the desired receptor affinity for 5HT7, as it has been implicated in providing the more utterly mind-blowing power of psychedelics. I entered these modifications into the NNLS optimizer and the output I got was**:

0.48*2C-B + 0.337*5-MeO-DMT + 0.116*MDMA + 0.043*cis-2a + 0.016*6-F-DMT + 0.005*Mescaline

I see, so since 2C-B is still the backbone of the desired affinity pattern, it appears in high proportion in the mixture as a kind of “base” on top of which the modifications are made. It makes sense that 5-MeO-DMT would come next as it is pretty selective for 5HT7 (remember, the most literally mind-blowing chemical), and MDMA would follow due to the desire for Imidazoline affinity. That by the way, is also probably partly why the formula contains a pinch of Mescaline, to round up that Imidazoline for good measure. I then decided to relax the 5HT7 requirement and instead increase the 5HT6 and 5HT5A, and got the following formula:

0.038*Lisuride + 0.273*2C-B + 0.056*DMT +0.079*Mescaline + 0.15*MDMA + 0.377*RR-2b + 0.018*Ibogaine

And this now looks pretty different. After playing like this for a while, it occurred to me to use this technique to basically try to reconstruct a drug using a non-negative linear combination of the remaining drugs available. Imagine for example that you are stuck in quarantine at your house and you don’t have any 2C-B to kill time (I know! Very relatable isn’t it?), but you do somehow happen to have an assortment of hundreds of other unscheduled random research chemicals. Could you combine them in such a way that you approximate the effects of 2C-B? Well, let’s see.

Here are the “drug reconstructions” the method derives (again, please, don’t try this at home):

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I am pleasantly surprised to see the formulas actually do seem pretty intuitive to me. Take for example the DIPT reconstruction. The top two ingredients are 5-MeO-DIPT and DPT, which are the two closest structural analogues of DIPT in the dataset. Or take the one for DOB: this is the amphetamine version of 2C-B, so it makes sense that both an amphetamine psychedelic (Aleph-2) and 2C-B would make up the top two ingredients. Or consider 5-MeO-DMT, with its most prominent ingredient being 5-MeO-TMT, which is one carbon atom away in terms of structure. Or see how Mescaline’s heart-opening effects are well represented by its reconstruction with MDMA and MDA, while TMA contributes the receptor affinity characteristic of the trimethoxy class of functional groups, along with another Mescaline-like phenethylamine, 4C-T-2. Alas, here is where an imperfect understanding of drug interactions could come and bite us in the ass: if 4C-T-2 is anything like 2C-T-2, it might have some MAOI action, which could be potentially very dangerous to combine with compounds like MDMA. Needless to say, before you go out and try these crazy drug cocktails, we first need a thorough understanding of each drug well beyond just its affinity to “only” 30 or so receptors.

Now, not every reconstruction makes sense to me, and really only a few substances have what I would call a descent mean squared error. See the receptor affinity tables below for examples of both successful and unsuccessful reconstructions (only non-zero entries shown):

DOB and 2C-T-2 have some of the lowest errors in the sample, meaning that their reconstructions are pretty good, while Ibogaine and MDMA have two of the worst error rates, and their reconstructions are still obviously pretty far from the goal. Naturally, if we were ever to test this method in the lab (with e.g. a drug discrimination paradigm) we would probably start with the most accurate reconstructions first. For instance, train rats to distinguish between 2C-B and DOB, and see if administering the (2C-B-containing) “DOB reconstruction” makes the rats think they got DOB rather than 2C-B.

Master Druggist (Synapse? Dendrite?)

I would like to conclude this essay with an interesting speculation: what if we developed drug combos like we develop perfumes? It is my appreciation that it takes a very high level of intelligence, domain expertise, and psychological robustness to be able to contribute usefully to the field of psychonautics. Sasha Shulgin spent over 30 years taking hundreds of completely new drugs, and I would very much trust his judgement about what makes a great psychedelic drug combo than I would trust a random BlueLight or Erowid user. (As an aside: Shulgin was extremely cautious in his approach, but he certainly wasn’t doing some of the low-hanging fruit on safety, such as wearing a heart monitor or measuring his blood pressure when taking a new drug, for starters. Future systematic psychonautic work should also record as much biometric data as is feasible). You wouldn’t put on a perfume made by someone who has only ever worn Axe, would you? Training a “Nose” takes up to 7 years, and it involves becoming deeply familiar with the scent of a long list of molecules, accords, and perfumes. Likewise, I’d expect that in order to be qualified to find extremely good drug combinations, one would first need to become familiar with the effect of many different individual drugs, “natural drug accords” (e.g. peyote), and designed drug cocktails. Only once you have an intuitive sense of how e.g. the sigma receptor interacts with the 5HT1A receptor would I trust your judgement about adding a pinch of agmatine to your already convoluted mixture of 20 psychoactive substances. A Super-Shulgin Academy could train people to be professional drug cocktail makers (if perfumers are called “Noses” would we call Super-Shulgin certified cocktail makers “Dendrites”?). As discussed above, this assumes that we can do this safely, which I suspect will be possible once we map out the space of dangerous combinations and receptors we shouldn’t mess with to avoid side effects like cardiotoxicity (e.g. 5HT2B, 5HT3A, calcium channels, etc.).

You come to the master cocktail designer with a general concept for a new recreational drug, and they would come up with activity profiles that best evoke those feelings. The Dendrite would select from hundreds or thousands*** of pure chemicals and accords to create your unique cocktail. As is the case with Noses in the perfume industry, a Dendrite would tend to have a set of about one to two hundred “frequently used” compounds, and a dozen or so “signature” ones they’re deeply familiar with and that usually reveal who the Druggist is, if found in large proportions in the end product. Of course there would be “house favorites” (e.g. the classic “ambroxan bomb” of Dior fragrances for men) and chemical fads (e.g. the wide adoption of Iso E Super in 90s perfumes). Every year would come with a new season of amazing, safe, and uniquely interesting recreational drug cocktails.

In perfumery you find both natural and synthetic “accords”: “Violet reconstructions” attempt to emulate the smell of violet but in a much more long-lasting, storable, and versatile way. Good Dendrites would not only use “natural accords” such as “peyote” or “marijuana plant” but would also make their own, aided with computer models and datasets of trip reports along with their own first person experiences. In both perfumery and professional drug cocktail making we would study accords packed with combos of qualia-triggering chemicals, and a Dendrite could be known not only for making good final products, but for making excellent accords with predictable and desirable effects.

To finalize the analogy (and this article) we could also discuss the way in which perfumes feel “broad spectrum” thanks to being constructed by combining “top, heart, and base notes”. Roughly speaking, top notes tend to “feel higher frequency” (such as citric scents) while base notes tend to “feel low frequency” (such as woody scents), not unlike how a symphony will tend to combine sounds across the spectrum. The most interesting, voluptuous, and commercially viable combos would also probably have a broad spectrum of activity. They would be anxiolytic, exciting, relaxing, trippy, and empathogenic to various degrees all at once. They would combine fast, slow, and spiritual euphoria in a single power punch of qualia cornucopia. As such, each drug cocktail made this way would entail an entire worldview – a whole realm currently hidden in the vast state-space of consciousness.



* For an intuition: recall from linear algebra that a basis of n linearly independent vectors span an n-dimensional vector space. When the vector that you are trying to reconstruct is not in the span of your basis, the best you can do is to project your vector to the nearest hyperplane of the spanning space. Adding the constraint that you can only make non-negative linear combinations with your basis vectors, you find that the span will look like an ‘inverted pyramid’, and the least-squares solution will be the point of that inverted pyramid that is closest to your desired vector. This is why most of the reconstructions only use a subset of the available drugs in the dataset. In most cases, the desired vector (i.e. affinity profile in this case) will be outside of the inverted pyramid of the non-negative span, and the closest hyperplane will be a linear combination of only a subset of the building blocks- those which span that particular hyperplane. I.e. the solution is the projection to the nearest hyperplane segment covering the non-negative span. This is what the NNLS method is doing under the hood.

** Note: It’s important to point out that these are not dosages. The coefficients provided by the non-negative least squares method apply to the normalized affinity “npKi“, which is the receptor affinity normalized by the highest affinity among the receptors. The coefficients will be correlated with “proportion of a standard active dose” but there will be an error caused by the pretty tricky confounder that molecules vary in their “breadth of affinity”. Additionally: the psychoactivity of each receptor is not the same, we are not considering saturation effects, the difference between partial and full agonists is not taken into account, downstream effects are ignored, etc. etc. Needless to say, there is still quite some work to be done to transform these coefficients into meaningful dosages.

*** List of Psychoactive Drugs a professional Dendrite would be expected to be familiar with:

L-Tyrosine, L-DOPA, Apomorphine, Flumazenil, CPZ, BPAP, PPAP, Cabergoline, DAR-0100, Lisuride, Pergolide, Pramipexole, Rotigotine, Biopterin, PLP, Aminepetine, PCP, Marijuana, Dextromethorphan, Isoflavones, Citicoline, Metadoxine, Arecoline, Niacinamide, Paraxanthine, a-GPC, Acetylcarnitine, AR-R17779, GTS-21, Ispronidine, PHA-543,613, SSR-180,711, WAY-317,538, Hopantenic Acid, IDRA-21, Propentofylline, PRL-8-53, Trytophan, Picamilon, Betahistine, A-349,821, Cipoxifan, Creatine, Mildronate, Pregnenolone, Nisoxetine, Orexin, CP-39,332, Esreboxetine, Daledalin, AM-1248, Phenoxybenzamine, Symbescaline, Phentolamine, Isomescaline, Tolazoline, a-Methylfentanyl, Ketamine, Dichlorpane, 3-meo-pcp, Hex-en, Paraflourofentanyl, 3-Methylfentanyl, Metofoline, Buscaline, O-DT, Nortilidine, Thiobuscaline, Dizocilpine, Rolicyclidine, Phenescaline, Tenocyclidine, Methoxyketamine, pFPP, 5-me-MDA, 4-MAR, 1,4-Butanediol, 2-Methyl-2-Butynol, GHV, GVL, Mebroqualone, Benzylbutylbarbituates, Phenmetrazine, 3-Fluorophenmetrazine, Crack, Cocaine, Coca, Kava, Phenylacetylindoles, Benzoylindoles, Napthoylindoles, Adamantoyindoles, Pineapple Sage, Kokum, Brahmi, Artic Weed, Skullcap, Salvia Splendens, Coriander, Rhodiola Rosea, Velvet Bean, Bitter Orange, St. John’s Worth, Grape Seed Extract, Tulsi, Blessed Thistle, 3-Desoxy-MDA, Skatole, Isoindole, Indole, Benztropine, Diphenhydramine, Niaprazin, Doxylamine, Alaproclate, Zopiclone, Ifoxetine, Methylmethaqualone, Panuramine, Meta-Tyramine, Para-Tyramine, 2M2B, Pirandamine, SB-649,915, Epinephrine, Mepyramine, Octopamin, Delucemine, Oxidopamine, β-Methylphenethylamine, Mesembrine, Psuedoephedrine, Etolorex, Cathine, Cathinone, Ethcathinone, Norfenfluramine, Fenfluramine, Phentermine, Metaescaline, n-Ethylbuphedrone, Naphyrone, Pyrovalerone, Isopropylamphertamine, Clobenzorex, Pholedrine, Chlorphentermine, Xylopropamine, DON, DOPR, TMA, Methyl-BOB, Tetramethoxyamphetamine, 4-MTA, Bromatane, Hydroxyzine, BNC-210, CL-218,872, L-838,417, SL-651,498, S32212, 6-CAT, TAP, ETAI, IMP, Lorxaserin, Cisapride, Tegaserod, AS-19, E-55888, LP-12, LP-44, LP-211, Etoperidone, Lorpiprazole, Lubazodone, Mepiperazole, 5-TASB, TB, 3-TE, 4-TE, 2-TIM, 3-TIM, 4-TIM, 3-TM, 4-TM, TMA, TMA-2, TMA-3, TMA-4, TMA-5, TMA-6, 3-TME, 4-TME, 5-TME, 2T-MMDA-3a, 4T-MMDA-2, TMPEA, 2-TOET, 5-TOET, 2-TOM, 5-TOM, TOMSO, TP, TRIS, 3-TSB, 4-TSB, 3-T-TRIS, 4-T-TRIS, 44-BMAR, 3-MOMC, Prolintane, SDB-001, AB-FUBINACA, Dichloromethylphenidate, AB-PINACA, MN-24, 5F-MN25, A-836,339, ADBICA, 5F-NNEI, RCS-4, RCS-8, MPHP, 6-APDB, 4-HMP, EDMA, a-PBP, Methylhexamine, a-PPP, 4-FMD, EIDA, Phenylphrine, UWA-101, MPBP, RH-34, F-2, F-22, MR-2096, Adrenochrome, AET, Carbogen, DOB, DOM, Desmorphine, Ethylcathinone, Ehylene, GHV, Hypocretin, mCPP, MDPR, Methaqualone, TFMPP, CPP, MeoPP, A2, Salvinorin A, Scoplamine, TMA-2, BDO, 2c-B-FLY, 4-Flouromethcathinone, 4-HO-MPT, U4EA, 4-MTA, Phenylpiracetam, Aniracetam, Coluracetam, Pramiracetam, Melatonin, NRG-3, Theobromine, A834-735, Oxytocin, NZT-48, Heroine, 3-HO-PCP, MAOIs, 4-MeO-PCP, 3c-P, 5-IAI, Atropine, 5-IT, Bufotenin, 5-MAPB, 4-Aco-MiPT, 6-MAPB, ALD-52, AMMI, MET, D2PM, DET, CBD, CBN, LY-2183240, SF-SDB-005, AM-404, EG-018, DXM, FDU-PB22, AL-LAD, 3-MeOMC, 2-MeO-Diphenidine, 4-MPD, bk-MDMA, 4-MeO-a-PVP, GHB, 4-MeO-PBP, MBDB, 4-MeO-PV9, Fentanyl, 4F-PV8, a-PBT, BDB, a-PVT, 2-FMA, Dibutylone, 5-Meo-DiPT, Diclofensine, Methcathinone, DL-4662, MDEA, MDPPP, Methylone, Butylone, NEB, Phenibut, PV-8, GABA, 25B-NBF, Etaqualone, 5-API, Ethylone, Pentadrone, 4F-PVP, 25C-NBF, BZ-6378, C30-NBOMe, RH-34, MDAT, MDMA, MDMAI, Dimethocaine, Synthacaine, 3β-FBT, 5-MeO-BFE, 3,4-DMMC, AM-1248, MTTA, AM-2233, URB-597, AM-694, AM-087, BAY-38-7271, AB-005, A-796260, URB-754, 2-DPMP, a-PVP, 25N-NBOMe, 5-MeO-NiPT, Dexmethylphenidate, Buphedrone, RTI-111, Pentylone, 25I-NBF, Flourotropacocaine, Flourococaine, Cocaethylene, 25D-NBOMe, 25E-NBOMe, DMT, 5-Meo-DMT, 2C-I, 2C-E, 25I-NBOMe, 25I-NBOH, 25C-NBOMe, MXE, MDA, MDE, Mescaline, Ibogaine, Bromo-DragonFLY, Salvinorum, RU-28306, 2NE1, Psilocybin, HOT-7, JWH-018, JWH-250, 5-Meo-EiPT, AM-2201, 5-APDI, BZP, BZ, 4-MEC, MDPV, Bakers Ammonia, THC, THCv, Chloral, Chlorabutynol, MT-45, 5-Methyl-Ethylone, Methylphenidate, Ethylphenidate, 6-APB, 5-APB, Muscimol, 5-MeO-MALT, AKB48, 3,4-CTMP, PB-22, Diphenidine, UR-144, Flubromazepam, HU-210, MPA, XLR-11, MN-18, Naltrexone, STS-135, Gabapentin, 5-MAPB, Nitrous, Etizolam, Mephedrone, Pyrazolam, Methedrone, AH-7921, Phenazepam, AMT, OxyNEO, DPT, 5-MeO-AET, 4-Aco-DMT, EAM-2201, 5-MeO-DALT, 5-MeO-AMT, Acefentanyl, Ehylphenidate, 4-HO-MiPT, THJ-2201, 5-APDB, 5-EAPB, 4-HO-DPT, DOC, bk-2c-B, Escaline, THJ-018, 4-HO-MET, 2-AI, 2-MeO-Ketamine, Methoxphenidine, Ketamine, 2c-EF, Methamphetamine, Dextroamphetamine, Nitracaine, DALT, IAP, 4-fa, 2-Me-DMT, 4-fcocaine, Isopropyl Nitrate, 5-MeO-TMT, Piracetam, Amatadine, Choline, Memantine, 5-HTP, Camfetamine, Methallyescaline, LSZ, LSA, NBOMe-Mescaline, Loperamide, LSB, 25P-NBOMe, 25G-NBOMe, 3-MeO-PCE, MAM-2201, PCP, MPTP, MDAI, DOI, BB-22, EA-3167, BDF, L-Theanine, Dimethylone, Hydrocodone, Codeine, Morphine, Dilaudid, Oxycontin, Alpralozam, Diazepam, Fentanyl, Soma, Suboxone, Marinol, Seroquell, Trazodone, Lithium Bicarbonate, Abilify, Methadone, Amitriptyline, Strattera, Chloral Hydrate, Bromazepam, Buperonorphrine, Bupropion, Chlordiazepoxide, Clonidine,Clonazepam, Cyclobenzaprine, Dramamine, Benadryl, Ethchlorvynol, Fluoxetine, Tianeptine, Amineptine, Flurazepam, Metaxalone, Mirtazapine, Nalaxone, Nimetazepam, Oxymorphone, Paroxetine, Zopidone, Pregabalin, Promethazine, Risperadone, Selegiline, Sertraline, Sumatripan, Tiagabine, Propofol, Propanolol, Tiletamine, Zolpidem, Lotus, Aloe, Datura, Calendula, Chacruna, Galangal, Chaliponga, Chamomile, Damiana, Fever Few, Nightshade, Ginseng, Foxglove, Lavender, Henbane, Mugwort, Hemlock, Monkshood, Dream Herb, Capsaicin, Amanita, Hawaiian Baby Woodrose, Ergot, Hops, Imphepho, Indian Warrior, Kanna, Dagga, Kratom, Mandrake, Valerian, Nicotiana Tobacum, Nicotiana Rustica, Mimosa Hostilis, Morning Glory, Nutmeg, Opium Lettuce, Poppy, Sinicuichi, Syrian Rue, Tree Tobacco, Wormwood, Yohimbe, Yopo, Khat, Peyote, Cannabis, Catnip, Phalaris, San Pedro, Soma (ancient), Chacruna, Acacia, Ephedra, Mulungu, Mullet Fish, Siganus Spinus, Fugu, Sting-ray Venom, Bufo Alvarius, Epipedobates Tricolor, Waxy Monkey Frog, Salamandra Salamandra, Cobra & Scorpion Venom, Reindeer Urine, Glomeris Marginata, Sergeant Major, Grouper, Bluefish, Brass Beam, Flathead Mullet, Golden Goatfish, Rabbit Fish, Goat Fish, Adrafinil, DHEA, Dilantin, DMAE, Fipexide, Gerovital, Ginko, Black seed oil, HGH, Hydeigine, Meclofenoxate, Modafinil, Oxiracetam, Phenyton, Vasopressin, Vinopocetine, Bee Venom, Monkey Frog, UCM-707, AM-1172, VDM-11, VDM-13, OMDM1, OMDM2, LY-2318912, O-2093, OL-135, URB-597, URB-532, AEM, AL, ALEPH, ALEPH-2, ALEPH-4, ALEPH-6, ALEPH-7, ARIANDE, ASB, B, BEATRICE, BIS-TOM, BOB, BOH, BOHD, BOM, 4-Br-3,5-DMA, 3-Br-4,5-MDA, 2C-B, 3C-BZ, 2C-C, 2C-D, 3C-E, 2C-F, 2C-G, 2C-G-3, 2C-G-4, 2C-G-5, 2C-G-N, 2C-H, 2C-N, 2C-O-4, 2C-P, CPM, 2C-SE, 2C-T, 2C-T-4, 2C-T-2, 2C-T-7, Ψ-2C-T-4, 2C-T-8, 2C-T-9, 2C-T-13, 2C-T-15, 2C-T-17, 2C-T-21, 4-D, β-D, DESOXY, 2,4-DMA, 2,5-DMA, 3,4-DMA, DMCPA, DMMDA, DMMDA-2, DMPEA, DOAM, DOBU, DOEF, DOET, Ψ-DOM, DON, DOPR, E, EEE, EEM, EME, EMM, ETHYL-J, ETHYL-K, FLEA, G-3, G-4, G-5, GANESHA, G-N, HOT-2, HOT-17, IDNNA, IM, IP, IRIS, J, LOPHOPHINE, M, 4-MA, MADAM-6, MAL, MDAL, MDBU, MDBZ, MDCPM, MDDM, MDHOET, MDIP, MDMC, MDMEO, MDMEOET, MDMP, MDOH, MDPEA, MDPH, MDPL, MDPR, ME, MEDA, MEE, MEM, MEPEA, META-DOB, META-DOT, METHYL-DMA, METHYL-DOB, METHYL-J, METHYL-K, METHYL-MA, METHYL-MMDA-2, MMDA, MMDA-2, MMDA-3a, MMDA-3b, MP, MME, MPM, ORTHO-DOT, P, PE, PEA, PROPYNYL, SB, TA, 3-TASB, 4-TASB, Tropane, Vomeronasal Organ, Tropine, Hyosyamin, Dihydrokavain, Hyoscine, Myrcene, Ecgonine, 7-OH-DPAT, Benzoylecgonine, Sunifiram, Hydroxytropacocaine, Estrogen, Methylegonine Cinnamate, Estradiol, Catuabines, Estratetraenol, Phenyltropane, Androstenone, Civetone, Adrostenol, 5F-PB-22, Androstadienone, CBG, THCa, CBC, CBDa, Anandamide, 2-AG, CBL, CBDv, CBCv, CBGv, CBGm, Ibogaine, Noribogaine, Tabernanthine, Coronaridine, Ibogamine, Vaocangine, 18-MC, 5-MeO-Alkyltryptamine, β-Carboline, Tryptoline, Pinoline, Harmane, Harmaline, Harmine, Harmalol, Harmalan, Harmanamide, Acetylnorhormine, Bufotenin Oxide, DMT-N-Oxide, 5-MeO-Tryptamine, 5-OH-DMT, 5-MeO-DMT-Oxide, 3,4-Dimethoxyphenylamine, 6-MeO-Harman, Anethole, Safrole, Estragole, Monolignol, Pukateine, Glaucine, THP, Nantenine, Thujone, Lagochilin, Nicotine, Carbachol, Methacholine, ME-18-MC, 18-MAC, Tryptamine, β-Methyl-Phenethylamine, NMT, Voacanga Africana, Vachellia Farnesiana, Duboisia Hopwood, Acacia Victoriae, Anadenanthera Penegrina, Phalaris Aquatica, Echinopsis Lageniformus, Cylindropuntia Echinocarpa, Leptactina Densiflora, Fennel, Justica Pectoralis, Lactucarium, Glacium Flavum, Zornia Latifolia, Argemone Mexicana, Silene Undulata, Catharanthus Roseus, Desfontainia, Heimia Salicifolia, Lophophora, Sea Urchin Eggs, Bethanechol, Muscarine, Pilocarpine, Oxotremorine, Aporphine, Leonurine, Bungacotoxin, Tetrodotoxin, Taurine, Opiod Peptide, Streamlined Spinefoot, Blue-Spotted Spinefoot, Dusky Spinefoot, Marbled Spinefoot, Little Spinefoot, Salema, Phyllomedusa, Blue Sea Chub, Brow Chub, Conuict Surgeonfish, Yellowstipe Goatfish, Finstripe Goatfish, Acute Jawed Mullet, Coral Grouper, Platypus Venom, Slow Ioris Venom, Pygmy Slow Ioris Venom, Giant Leaf Frog, Gluten Exorphin, Soymorphin-5, Dermophin, 7-PET, Dimethyliambutene, Proopiomelanocortin, β-Endorphine, Dynorphin, Adrenorphin, Salvinorin B Methoxymethyl ether, Amindophin, Enkephalins, Salvinorin B ethoxymethyl ether, Opiorphin, Herkinorin, RB-101, DPI-221, Spinorphin, Kelatorphan, Delta-Pheylalanine, Thiorphan, Tynorphin, Hemorphon-4, Valorphin, Casomorphin, Gliadorphin, Rubiscolin, Deltorphin, MG6, MT-45, Myrophine, Acetorphine, Acetylmorphone, Actiq, Benzethidine, BU-48, BRL-52537, Pethidine, Naloxol, Betacetylmethadol, Methorphan, Bezitramide, RAM-378, Bromadol, Eriadoline, BW373U86, Thebaine, C-8813, Menthol, 8-CAC, Capperidine, Matrine, Chloromorphide, a-Chlorocodide, HZ-2, Codeinone, LPK-26, Codoxime, AD-1211, Conorfone, DADLE, Butorphanol, DAMGO, Semorphone, Dextromoramide, Sutentanil, Diampromide, Zenazocine, Difenoxin, Thebacon, Dihydroetorphine, Tilidene, Dimenoxadol, Xorphanol, Dipipanone, Dipropanoylmorphine, Doxpicomine, DPI-3290, Drotebanol, Endomorphin, Eseroline, Ethoheptacine, 14-Ethoxymetopon, Ethylmorphine, Etorphine, Etoxerdine, Furethidine, Heterocodeine, RAM-320, IBNtxA, IC-26, 1-Iodomorphine, Isomethadone, Ketobemidone, Ketorfanol, Lefetamine, Levorphanol, Loperamide, Meprodine, Metofoline, Metopon, Morpheridine, Morphine-N-Oxide, Morphinone, MR-2096, Nicocodeine, Nicomorphine, Normethadone, Ocefentanyl, Ohmefentanyl, Oxpheneridine, Oxymorphazone, Oxymorphol, Oxymorphone, Pentamorphone, PEPAP, Pericine, Phenadoxone, Phenempromide, Phenazocine, Pheneridrine, Phenomorphan, Picenadol, Piminodine, Piritramide, Proclilidine, Prodine, Proheptazine, Properidine, Prosidol, R-30490, R-4066, Ro4-1539, RWJ-394674, Sameridine, SC-17599, Methyldesorphine, Hydroxypethidine, 4-Fluouropethidine, Cannabis Indica, Cannabis Sativa, Cubensis, Hash, BHO, Delta-9-THC, 25TFM-NBOMe, 2C-B-BZP, 2CBFLY-NBOMe, 2CD-5Et0, 5-I-R91150, A-372,159, 2-Bromo-LSD, a-5IA, PWZ-029, L-655,708, TB-21007, 5-Ethoxy-DMT, 5-Ethyl-DMT, 7,N,N-TMT, VER-3323, YM-348, Alnespirone, 8-OH-DPAT, Aminorex, Batoprazine, 5-BT, BIMU-8, BMY-14802, BRL-54443, BW-723C86, 5-CT, CGS-12066A, Cinitapride, CJ-033,466, CP-135,807, CP-809,101, CP-93,129, CP-94,253, N,a,-DEPEA, Dimemebfe, RA-7, E-6801, E-6837, Eltoprazine, Methylsulfonylmethane, EMD-386,088, EMDT, ST-1936, Fluprazine, Indorenate, Jimscaline, L-694,247, Lasmiditan, APD-356, MMDPEA, LY-293,284, LY-310,762, LSD-pip, LPD-824, LSM-775, 5-MT, MBZP, Methyl-MMDA-2, a-MS, MK-212, Mosapride, Org 12,962, Org 37,684, Quipazine, 6-Nitroquipazine, NBUMP, 1-NP, 5-(Nonyloxy)Tryptamine, PHA-57378, PNU-181731, PNU-22394, Propylhexedrine, Prucalopride, PRX-03140, Psilocin, RDS-127, RH-34, Ro60-0175, Ro60-0213, RS-56812, RS-67,333, RU-24,969, RU-28306, SKF-97,541, SR-57227, Tandospirone, Tegaserod, TFMFly, pTMFPP, U-92,016A, SCA-136, TD-5108, Vortionetine, WAY-161503, WAY-208,466, WAY-629, Xaliproden, YM-31636, Zacopride, A-423,579, A-84,543, Abercarnil, 5-Br-DMT, Sugar, Acetildenafil AMMI 4C-D, AS-8112, Astemizole, Asymbescaline, Azapride, BAY-38-7271, BAY-59-3074, BAY-60-6583, Benproperine, Benzylmorphine, Berberine, 2-Pyrrolidone, JBIR-03(1), 1′-O-Acetylpaxilline, Penijanthine A, Emindole DA (1), Petromindole, Emindole SA (2), JWH-133, Napthylmethylindoles, Napthyolpyrroles, Napthylideneindenes, Cyclohexylphenols, Indole-2-Carboxamides, C3 Amino-Indoles, Cymserine, Hodgkinsine, Physostigmine, Psychotridine, Psychotria Colrata, Yuremamine, Gevotroline, Latrepirdine, BMY-7,378, Boldine, BP-897, Brexpiprazole, 4-Bromo-3,5-Dimethoxyamphetamine, Bromopride, Caroverine, CGS-20625, Cinchocaine, DAA-1097, DAA-1106, DOTFM, DMPEA, DMCM, Dyclonine, Ethylvanilin, Evoxine, Furoquinoline Alkaloids, Gabazine, GBLD-345, Rapacuronium, Mivacurium Chloride, Cisatracurium Besilate, DTC, Cloroqualone, Diproqualone, Mecloqualone, Methylmethaqualone, Eszopiclone, TP-003, TP-13, TPA-023, Y-23684, Pagoclone, Pazinaclone, Suproclone, Suriclone, Zapiclone, CGS-9896, NS-2664, NS-2710, Pipequaline, RWJ-51204, SB-205,384, ELB-139, Acamprosate, GABOB, N4-Chloroacetylcytosine Arabinoside, (+)-CAMP, CACA, AZD-3355, 1,4-Butanediol, XP19986, Rosarin, Rosavarin, Atagabalin, Gabapentin Enacarbit, Hopantenic Acid, Imagabalin, 4-Methylpregabalin, PD-217,014, Afloqualone, Rocuronium Bromide, Vecuronium Bromide, Pipecuronium Bromide, Pancuronium Bromide, Amyl Nitrate, Atracurium Besilate, BWA444, Benzylisoqualone, Papaverine, Protopine, HS-342, HS-347, HS-310, Emylcamate, Eperisone, Febarbamate, Flavoxate, Inaperisone, Acamprosate, Progabide, Tiagabine, Lanperisone, Mephenesin, HS-692, HS-693, HS-704, HS-705, HS-626, Chlorzoxazone, Cisatracurium Besilate, Curare, Cyclobenzapine, Dantrolene, Decamethonium, Difebarbamate, Dihydrochanclonium, Doxacurium Chloride, Gallamine Triethiodide, Gantacurium Chloride, Hexafluronium Bromide, Meprobamate, Metaxalone, Methocarbamol, Norgesic, Orphenadrine, Pancuronium Bromide, Phenprobamate, Pipecuronium Bromide, Premazepam, Promoxolane, Quazepam, Rocuronium Bromide, Silperisone, Sulazepam, Suxamethonium Chloride, Suxethonium Chloride, Tetrabamate, Tizanidine, Tolperisone, Gigantine, BAY-73-6691, Indiplon, Nitrosoprodenafill, Zaleplon, Udenafil, Sulfoaildenafill, Sildenafil, Ocinaplon, Alpidem, Bamaluzole, DS-1, Fadrozole, Fazadinium Bromide, Imidazopyridine, Minodronic Acid, Bisphosphonate, Miroprofen, Necopidem, AL-LAD, DBT, a.O-DMS, 2,a-DMT, a,N-DMT, ETH-LAD, a-ET, 4-HO-DBT, 4-HO-pyr-T, MBT, 4,5-MDO-DIPT, 5,6-MDO-DIPT, 4,5-MDO-DMT, 5,6-MDO-DMT, 5,6-MDO-MIPT, 5,6-MeO-MIPT, 5-MeO-pyr-T, 5-MeO-NMT, 6-MeO-THH, 5-MeS-DMT, PRO-LAD, pyr-T, a,N,O-TMS, Olprinone, Telcagepant, Febrifugine, Halofuginone, MK-0249, LY-156,735, Ramelteon, Tasimelteon, SL-164, Quinazoline, Albaconazole, Altaserin, ATC-0175, Canertinib, Cediranib, Doxazosin, Fluproquazone, Gefitinib, Katanserin, Lapatinib, Agmatine, Amantadine, AP-7, AP5, Aptiganel, CGP-37849, 7-CTKA, DCKA, DXO, MK-801, SL-82.0715, Esketamine, Ethanol, NEFA, Besonprodil, Gacyclidine, Gavestinel, Huperzine A, Ifenprodil, Indantadol, Metaphit, Memantine, LY-235,959, Lubeluzole, Levomethadone, Kynuretic Acid, Midafotel, Neramexane, Nitromemantine, PEAQX, Perzinfotel, 8A-PHDQ, Remacemide, Rhynchophylline, Sabeluzole, Tiletamine, Tramadol, Xenon, Hydroxchloroquine, Antrafenine, Bedaquiline, GSK-299423, JTC-801, JTE-907, LGD-2226, PBT-2, PF-2545920, SB-215,505, SB-277,011-A, SB-742,457, BHF-177, BHFF, BSPP, Cartazolate, CGP-7930, Clomethiazole, Etazolate, Etomidate, Felbamate, Fospropofol, Gaboxadol, Glutethimide, GS-39783, Ibotenic Acid, ICI-190,622, Isoguracine, Isonipecotic Acid, Loreclezole, Methyprylone, Allopregnanolone, 5a-Dihydroprogesterone, Progesterone, THDOC, Alfadolone, Alfaxalone, Ganaxolone, Hydroxydione, Minaxolone, Org-20599, Pregnane, Piperadone, Propanidid, Propofol, Pyrithyldione, ROD-188, Stiripentol, Thiomuscimol, Thymol, Tybamate, QNB (BZ), Scopolamine, Midazolam, Sodium Pentathol, Amobarbital, Blue 88, Adinazolam, Alphenal, Bentazepam, Bromisoval, Camazepam, Carbromal, Centalun, Chloralodol, Chronobiotic, Cinolazepam, Clorazepate, Cloxazolam, Cyclopyrrolones, Delorazepam, Dichloralphenazone, DPH, Doxefazepam, Doxylamine, Embutramide, Eplivaserin, Ethinamate, Ethyl Ioflazepate, Fludiazipam, Heptabarb, Oleamide, Org 21465, Org 25435, Paraldehyde, Phenobarbital, Propiomazine, Promethazine, Propylbarbital, QH-II-66, Glycine, Quetiapine, SH-053-R-CH3-2’F, Sulfonmethane, Tetrabarbital, Tetronal, Trional, Trytophol, Acaprazine, Acebrochal, Acetylglycinamide Chloral, Almorexant, Detomidine, Bromouriede, Benzoctamine, Barakol, Bekhterev’s Mixture, Fasiplon, Fenadiazole, Fluperlapine, JM-1232, Inebriating Mint, Ro41-3696, Methapyrilene, Minitran, Nisobamate, Oxanamide, Oxomemazine, Panadiplon, Pazinaclone, Pentabamate, Petrichloral, Potassium Bromide, Procymate, Saripidem, Vinybital, Vinbarbital, Valofane, Validolum, Valeric Acid, Unisom, U-90042, U-89843A, Triclofos, 2,2,2-Trichloroethanol, TCS-OX2-29, SX-3228, Suvorexant, Sigmodal, SB-649,868, 6-APA, 77-LH-28-1, Adimolol, Alfentanil, Amedanil, Amedalin, BMS-564,929, Binospirone, Carburazepam, Clazolam, Clobazam, Clobenzepam, Clotiazepam, Thienodiazepine, Brotizolam, CP-14145, Cyclazodone, CSP-2503, Cycloserine, Cytisine, Demoxepam, Chlordizepoxide, Dibenzepin, Dihydroergocorine, Dihydroergocristine, DHEC, Dihydroergotamine, 17-DMAG, Dimiracetam, Doliracetam, Droperidol, Dihydrotestosterone, Dutasteride, Edaravone, EGIS-12,233, Elfazepam, Elzasonan, Enilospirone, Ergoloid, Ergotamine, Ergocrytine, Ergocristine, Ergovaline, Etazepine, Evodiamine, Fenmetramide, Fenozolone, Flunitrazepam, Flutazolam, Flutemazepam, Flutoprazepam, Fosazepam, GW-803,430, Halazepam, Haloxazolam, Herbimycin, Horsfiline, HT-0712, Icilin, Clazepam, Indoprofen, Ipsapirone, Isatin, Ketazolam, KF-26777, Lofendazepam, Lopirazepam, Loprazolam, Lorazepam, Lormetazepam, Menitrazepam, Meclonazepam, Menitrazepam, NMSP, Mexazolam, THCI, THCII, THCIII, THCIV, THCV, Mosapramine, Motrazepam, NBQX, Nevirapine, Nimetazepam, Nitrazepam, Nitrazepate, Nitroxazepine, Nordazepam, Nortetrazepam, Oxazepam, Oxatomide, Paliperidone, Prazepam, Pivoxazepam, Pirquinozol, Pirenzepine, Pinazepam, Pemoline, Paraxazone, Palonosterone, Proflazepam, Propizepine, Razobazam, Revospirone, Ripazepam, Ro15-4513, Ro48-6791, Ro48-8684, Ro5-2904, Ro5-4864, Ro64-6198, Ropinirole, RPL-554, RS-102,221, SL65.0155, Spiroxatrine, Temazepam, Tetrazepam, Thozalinone, Tolufazepam, Triflubazam, Vardenafil, Ziprasidone, Zolazepam, Zomebazam, Zometapine, Pyrazolodiazipines, Triazolodiazipines, Estazolam, Flubromazolam, Triazolam, Nitrobenzodiazepines, Pentazocine, 8-HO-PBZI, A-366,833, ABT-202, Sympathomimethies, ABT-239, ABT-418, Almotriptan, BD-1008, LR-132, BD-1031, Singma Agonists, BD-1018, 4-PPBP, Alazocine, BD-1052, Butinoline, Clemizole, CPHPC, Desoxy-D2PM, Citalopram, Ditolyguanidine, Escitalopram, Fluoxetine, Fluvoxamine, Tgmesine, L-697,384, PRE-084, S33005, SA-4503. Siramesine, Venlafaxine, Clonidine, VUT-8430, UR-AK49, Moroxydine, Altinicline, Anabasine, 3-Bromocytine, Bradanicline, Cotinine, Desformylflustrabromine, Dianicline, DMPP, Epibatidine, Epiboxidine, Lobeline, Myosmine, PNU-120,596, PNU-282,987, ABT-089,Rivanicline, RJR-2429, Phantasmidine, Sazetidine A, SIB-1553A, TC-1698, TC-1827, TC-2216, Tebanicline, 2,3,4,5-Tetrahydro-1,5-Methano-1H-3-Benzazepine, UB-165, Varenicline, FE-β-CPPIT, FB-β-CPPIT, RTI-336, NVP-AUY922, Pleconaril, RTI-177, RTI-371, Calea Ternifolia, African Dream Herb, Ambutonium Bromide, Hyoscamine, Ilex Guayusa, Abediterol, Aclidinium Bromide, Benzilycholine Mustard, Bevonium, Bornaprine, Cyanodothiepin, Darifenacin, Dexetimide, Dicycloverine, Etybenzatropine, Fenpiverinium, Fesoterodine, Homatropine, Hydroxyzine, Imidafenacin, Ipratropium Bromide, Methylatropine, Methylhomatropine, Octatropine Methylbromide, PD-0298029, PD-102,807, Pipenzolate, Piperidolate, Tiotropium Bromide, Anisodine, Benacytazine, Butylscopolamine, CAR-226,086, CAR-301,060, CAR-301,196, Caramiphen, Clidinium Bromide, Ditran, EA-3167, EA-3443, EA-3580, EA-3834, JB-318, JB-336, Methylscoplamin Bromide, Oxapium Iodide, Oxitropium Bromide, Polyfothine, Propiverine, Pyrrobutamine, Timepidium Bromide, Tridihexethyl, Tropatepine, WIN-2299, Amrutanjan, Abstral, Acetylmethadol, Acetyldihydrocodeine, Alletorphine, Anilopam, Axomadol, BC Powder, Befiradol, Benorilate, Betamethadol, Bicifadine, Butinazocine, Carbazocine, Celadrin, Chlorodyne, Cinchophen, Co-dydramol, Co-codamal, Cogazocine, Conolidine, Deltorphin I, Dezocine, Dimepheptanol, Dipyrocetyl, TRPV1 Receptor, Capsazepine, Dosulepin, Electroanalgesia, Epideral Steroid Injection, Eptazocine, Equianalgesic, Efazocine, Fedotozine, Filenadol, Fioricet, Fiorinal, Frakefamide, Hemprenorphine, 3-HM, Ibazocine, Levallorphan, Levomepromazine, Lufuradom, Magnesium Salicylate, Blue Prickly Poppy, Menabitan, A-40174, Dimethylhepylpyran, Metamizole, Metkefamide, Moramide, Morphiceptin, Moxazocine, Nafoxadol, Malmexone, Naproxen, Nefopam, Nimesulide, Naracymethadol, Norlevorphanol, Norpipanone, NS-11394, Panadol, Penthox Inhaler, Phenacetin, Phenazone, Phenazopyridine, Propyphenazone, Proxorphan, Resiniferatoxin, Rimazolium, Romifidine, RUB-A535, Salecylamide, Salonpas, Tectin, Tolfenamic Acid, Tenazocine, Ufenamate, Volazocine, Xylazine, Yangonin, Zinda Tilismath, Ziconotide, Anazocine, Bremazocine, Cyclazocine, EKC, Fluorophen, Gemazocine, Ketazocine, Metazocine, Quadazocine, Azocine, Benzazocine, 0-2545, DOU-216,303, Phenylethylpyrrolidine, GR-89696, HA-966, ICI-199,441, ICI-204,448, NNN, Nornicotine, Clemastine, PF-03654746, RTI-229, SB-269,970, U-50488, U-69,593, Bombesin, Bivaracetam, Cebaracetam, DEABL, Cromakalim, Doxapram, Dupracetam, Etiracetam, Fasoracetam, Imuracetam, Levetiracetam, Lidanserin, Nebracetam, Nefiracetam, Nicoracetam, Oxiracetam, Piperacetam, Seletracetam, MOPPP, MPBP, MPHP, MDPDP, MDPPP, Pyrovalone, a-PBP, a-PPP, Neuropeptides, Galanin, Neuropeptide Y, Enkephalin, Somatoslatin, CCK, Substance P, Neurotensin, TRH, Acepramazine, Aceprometazine, Acetanisol, Acetohexamide, Acetophenazine, Acetophenone, Acetosyringoine, 2-Acetylpyridine, Adrenalone, Anthrone, Apocynin, Avobenzone, Benzbromarone, Benziodarone, Benzoin, Butaperazine, CB-13, AM-6545, AZ-11713908, WIN-54,461, JWH-200, WIN-56,098,S-796,260, AM-1220, AM-1221, AM-1241, AM-2233, AM-630, AAI’s, CPE, GW-405,833, JWH-193, JWH-198, JWH-007, 3-Acetyl-6-Methoxybenzaldehyde, Aflobazole, AR-A000002, Azasestron, Bazinaprine, 3-Benzhydrylmorpholine, BML-190, Cobicistat, CYT387, Desmethylmoramide, Dioxaphetyl Butyrate, Edivoxetine, Epelsiban, Demoxytocin, Carbetocine, WAY-267,464, Atosiban, Eprobemide, L-371,257, L-368,899, Quinagolide, Terbutaline, 2CB-ind, 5-APDI, APICA, Donepezil, ICI-118,551, Indatraline, Indinavir, Ladostigil, Mutisianthol, PNU-99,194, S-15535, TAI, Zicronapine, Aleglitazar, Thromboxame Receptor Agonist, Verruculogen, Brevianamide, 2,5-DKP, Fellutanine, Phenylahistine, Plinabulin, Rugulosuvine, Fedrilate, Fenbutrazate, L-733,060, G-130, HC3, Indeloxazine, Levomoramide, Metostilenol, Molindone, Molracetam, Nimorazole, O-1057, O-1812, AM-2232, O-774, AM-2389, HHC, HU-243, Canbisol, Nabilone, 11-OH-THC, 2-AGE, Paxahexyl, THC-C4, AMG-36, AMG-41, AM-1235, AM-906, AM-365, O-2694, O-2372, O-2113, O-2050, VCHSR, TM-38837, PiplSB, PF-514273, MK-9470, LY-320,135, O-2545, PD-128,907, PF-219,061, ABT-670, ABT-742, UK-414,495, OSU-6162, Melanotan II, Oxaflozane, PF-592,379, 2-Phenyl-3,6-Dimethylmorpholine, Pramocaine, SCH-50911, 4-HTMPIPO, A-41988, AB-001, AB-005, ADBICA, AM-087, AM-411, KM-233, AM-679, AM-694, AM-855, AM-905, AM-919, AM-4030, AM-938, AM-251, AMG-1, AR-231,453, PSN-375,963, PSN-632,408, (C6)-CP-47,497, CCH, O-1871, CP-55,940, CP-47,497, CP-50,556’1, CP-55,244, Otenabant, (C9)-CP-47,497, CBS-0550, AVE-1625, GW-842,166x, HU-308, HU-336, HU-331, HU-320, Ajulemic Acid, JTE-7-31, A-834,735, MDA-19, S-444,823, JTE-907, JWH-015, JWH-019, JWH-030, JWH-047, JWH-048, JWH-051, JWH-057, JWH-081, SLV319, 2-Isopropyl-5-Methyl-1-(2,6-dihydroxy-4-nonphenyl)cyclohex-1-ene, HU-345, JWH-098, JWH-116, JWH-120, JWH-122, JWH-147, JWH-148, JWH-149, JWH-161, JWH-164, JWH-167, JWH-175, JWH-176, JWH-184, JWH-185, JWH-196, JWH-203, JWH-249, JWH-302, JWH-307, JWH-359, JWH-398, JWH-424, L-759,633, L-759,656, GW-405,833, Leelamine, NESS-0327, NESS-040C5, NMP-7, Nonabine, O-1125, O-1238, O-1269, O-806, O0823, Org-27569, Org-28312, LBP-1, Org-28611, Otenabant, Perrottetinene, PF-03550096, RCS-4, RCS-8, Rosonbrant, SDB-001, SDB-006, SER-601, Serinolamide A, THC-O-Phosphate, Tinabinol, VDM-11, Virohamine, A77636, Adafenoxate, Adapromine, Adatanserin, Bolmantalate, Bromantane, SR-142,948, 25B-NBOMe, 25I-NBMB, 25TFM-NBOMe, 5-MeO-NBpBiT, 2CBCB-NBOMe, 25CN-NBOH, Juncosamine, TCB-2, 6-Br-APB, Agelferin, Cridazepam, Meta-DOB, NGD-4715, Nicergoline, P7C3, SB-357,134, Sclerotia Truffle, 5-Flouro-aMT, 6-Flouro-aMT, Telepathine, AMDA, Amperozide, Cinaserin, Deramciclane, Fenanserin, Flibanserin, Glemanserin, Iferanserin, KML-010, LY-367,265, Pruvanserin, Rauwolscine, Setoperone, Spiperone, Volinanserin, Xlamidine, Altropane, ATI-2042, PIA, RTI-121, RTI-353, Tramethinib, SB-258,585, Lu-AE58054, MS-245, Ro04-6790, SB-271,046, SB-399,885, RTI-55, AC-262,356, 2′-Acetoxycocaine, Bemestron, Benzoylthiomethylecogine, Brasofesine, 2-CMT, Clobenztropine, Cocaethylene, Deptropine, Dichloropane, Diflouropine, Granisetron, 3-(p-Flourobenzoyloxy)tropane, p-ISOCOC, Methylvanillylecogonine, Norcocaine, NS-2359, RTI-126, WF-23, WF-33, WF-31, WF-11, BRL-46470, RTI-112, RTI-113, RTI-120, RTI-150, RTI-171, RTI-274, RTI-31, RTI-32, RTI-51, RTI-83, Thiophenyltropanes, MAT Inhibitor, Salicylmethylecgonine, Tesofesine, Troparil, WIN-35428, Amfonelic Acid, Oxolinc Acid, Tropisetron, Zatosetron, Dichloropane, RTI-336, RTI-126, Tropoxane, Poyo (Palm Wine), Tropicamide, Caffetin, Formic acid, Monocled Cobra, Sisa, Tramadol, Dazopride, Dolasetron, Amylocaine, Articaine, Bupivacaine, Butacaine, Chloroprocaine, Cyclomethycaine, Etidocaine, Hexylcaine, Levobupivacaine, Mepivacaine, Meprylcaine, Prilocaine, Proxymetacaine, Risocaine, Ropivacaine, Tetracaine, Trimecaine, Piperocaine, Metabutoxycaine, Adipiplon, Almitrine, ARRY-520, AZD5423, Cisapride, CP-226,269, CRL-40,941, DBL-583, Dexamethasone, DFMD, Methyldopa, Carbidopa, d-DOPA, L-DOPS, Octaflourocyclobutane, DFB, Didesmethylcitalopram, Elopiprazole, Phenylpiprazine, F-15,599, FGIN-127, Fletazepam, Flucindole, GR-159,897, LY-503,430, MPPF, PEPA, RS-127,445, S-23, SHA-68, SNAP-7941, SNAP-94847, TP-003, TPA-023, UH-301, Calycosin, Flavinoids, Psi-Tectorigenin, Blochanin A, Formononetin, Glyciten, Irigenin, Methoxyisoflavone, 5-O-Methylgenistein, 7-O-Methylluteone, Ononin, Pratensein, Prunetin, Retusin, Tectoridin, Tectorigenin, Barbigerone, Daidzein, Derrubone, Genistein, Ipriflavone, Irilone, Luteone, Orobol, Psuedobaotigenin, Wighteone, AMG-3, Nabazenil, Naboctate, a-Napthoflavone, 11-Nor-9-Carboxy-THC, Pirnabine, Apiol, Dillapiol, 1,3-Benzodioxole, Piperonal, beta-Asarone, Eleicin, Homovanyllyl Alcohol, Myristicin, 2-Bromo-4,5-Methylenedioxyamphetamine, Californidine, Chavicine, Cinoxacin, Dibutylone, Fenoverine, Befuraline, MDIP, MDMAI, MDPR, MDAL, ORTHO-MDA, MDP1P, MDP2P, Omiloxetine, Osemozotan, Piclozotan, Robalzotan, Ebalzotan, Sarlzotan, Piperine, Protokylol, Isoprenaline, Rhoeadine, MDMPEA, MMDPEA, MMDMPEA, MDIP, MDHOET, MDPL, GYKI-52895, Ungiminorine, NADA, Methylene blue, ECG, EGCG, EGC, Levonantradol, Cone Snail Venom, A-836,339, Abacavir, CYP-LAD, 2-Bromo-LSD, BU-LAD, DAM-57, DAL, Epicriptine, Ergometrine, Ergometrinine, Ergostine, ETH-LAD, LEA-32, Methylergometrine, MLD-41, LSP, LSH, MIPLA, PARGY-LAD, PRO-LAD, DCG-IV, DOV-102,677, MDCPM, MNTX, Amfonelic acid, J-113,397, SB-612,111, VUF-6002, DBM, Piberatine, Ilercimide, Dithranol, Divaplon, Ebastine, Flopropione, Iloperidone, Ketorolac, Melperone, NNC-38-1044, Tetralone, Cuscohydrine, Hygrine, 4-NEMD, Aceburic Acid, Amfecloral, Aprobarbital, Arfendazam, Benzobarbital, Benzylbutylbarbituate, Brallobarbital, Brophebarbital, Buthalitol, Carbubarb, Climazolam, Cyclobarbital, Cyclopentobarbital, and Acid (i.e. regular LSD).

(source)

A Big State-Space of Consciousness

Kenneth Shinozuka of Blank Horizons asks: Andrés, how long do you think it’ll take to fully map out the state space of consciousness? A thousand or a million years?

The state-space of consciousness is unimaginably large (and yet finite)

I think we will discover the core principles of a foundational theory of consciousness within a century or so. That is, we might find plausible solutions to Mike Johnsons’ 8 subproblems of consciousness and experimentally verify a specific formal theory of consciousness before 2100. That said, there is a very large distance between proving a certain formal theory of consciousness and having a good grasp of the state-space of consciousness.

Knowing Maxwell’s equations gives you a formal theory of electromagnetism. But even then, photons are hidden as an implication of the formalism; you need to do some work to find them in it. And that’s the tip of the iceberg; you would also find hidden in the formalism an array of exotic electromagnetic behavior that arise in unusual physical conditions such as those produced by metamaterials. The formalism is a first step to establish the fundamental constraints for what’s possible. What follows is filling in the gaps between the limits of physical possibility, which is a truly fantastical enterprise considering the range of possible permutations.Island_of_Stability_derived_from_Zagrebaev

A useful analogy here might be: even though we know all of the basic stable elements and many of their properties, we have only started mapping out the space of possible small molecules (e.g. there are ~10^60 bioactive drugs that have never been tested), and have yet to even begin the project in earnest of understanding what proteins can do. Or consider the number of options there are to make high-entropy alloys (alloys made with five or more metals). Or all the ways in which snowflakes of various materials can form, meaning that even when you are studying a single material it can form crystal structures of an incredibly varied nature. And then take into account the emergence of additional collective properties: physical systems can display a dazzling array of emergent exotic effects, from superconductivity and superradiance to Bose-Einstein condensates and fusion chain reactions. Exploring the state-space of material configurations and their emergent properties entails facing a combinatorial explosion of unexpected phenomena.

And this is the case in physics even though we know for a fact that there are only a bit over a hundred possible building blocks (i.e. the elements).

In the province of the mind, we do not yet have even that level of understanding. When it comes to the state-space of consciousness we do not have a corresponding credible “periodic table of qualia”. The range of possible experiences in normal everyday life is astronomical. Even so, the set of possible human sober experiences is a vanishing fraction of the set of possible DMT trips, which is itself a vanishing fraction of the set of possible DMT + LSD + ketamine + TMS + optogenetics + Generalized Wada Test + brain surgery experiences. Brace yourself for a state-space that grows supergeometrically with each variable you introduce.

If we are to truly grasp the state-space of consciousness, we should also take into account non-human animal qualia. And then further still, due to dual-aspect monism, we will need to go into things like understanding that high-entropy alloys themselves have qualia, and then Jupiter Brains, and Mike’s Fraggers, and Black Holes, and quantum fields in the inflation period, and so on. This entails a combinatorial explosion of the likes I don’t believe anyone is really grasping at the moment. We are talking about a monumental “monster” state-space far beyond the size of even the wildest dreams of full-time dreamers. So, I’d say -honestly- I think that mapping out the state-space of consciousness is going to take millions of years.

But isn’t the state-space of consciousness infinite, you ask?

Alas, no. There are two core limiting factors here – one is the speed of light (which entails the existence of gravitational collapse and hence limits to how much matter you can arrange in complex ways before a black hole arises) and the second one is quantum (de)coherence. If phenomenal binding requires fundamental physical properties such as quantum coherence, there will be a maximum limit to how much matter you can bind into a unitary “moment of experience“. Who knows what the limit is! But I doubt it’s the size of a galaxy – perhaps it is more like a Jupiter Brain, or maybe just the size of a large building. This greatly reduces the state-space of consciousness; after all, something finite, no matter how large, is infinitely smaller than something infinite!

But what if reality is continuous? Doesn’t that entail an infinite state-space?

I do not think that the discrete/continuous distinction meaningfully impacts the size of the state-space of consciousness. The reason is that at some point of degree of similarity between experiences you get “just noticeable differences” (JNDs). Even with the tiniest hint of true continuity in consciousness, the state-space would be infinite as a result. But the vast majority of those differences won’t matter: they can be swept under the rug to an extent because they can’t actually be “distinguished from the inside”. To make a good discrete approximation of the state-space, we would just need to divide the state-space into regions of equal area such that their diameter is a JND.15965332_1246551232103698_2088025318638395407_n

Conclusion

In summary, the state-space of consciousness is insanely large but not infinite. While I do think it is possible that the core underlying principles of consciousness (i.e. an empirically-adequate formalism) will be discovered this century or the next, I do not anticipate a substantive map of the state-space of consciousness to be available anytime soon. A truly comprehensive map would, I suspect, be only possible after millions of years of civilizational investment on the task.

Three Interesting Math Problems to Work on While on LSD

  1. Let P be a simple polygon with n>3 sides. A simple polygon is a polygon that does not self-intersect, but it is not necessarily convex. Prove that no matter the shape of P, there is always a diagonal (a segment that connects two vertices of P without intersecting any of its sides) that divides P into two polygons, both of which have at least n/3 sides.
  2. Let A and B be two points in the plane. Using only a compass and a straightedge, find the point C which is the exact middle point between A and B. Now do the same thing, but using only a compass.
  3. There are 17 point-sized light-houses in the plane. Assume that each of these lighthouses can shine light in any direction with an angle of 2*pi/17. Prove that no matter the position of each lighthouse, it is always possible to choose the angles at which they shine their light such that every point in the plane is illuminated (point-sized lighthouses don’t cast shadows).

In Selective Enhancement of Specific Capacities Through Psychedelic Training, Willis Harman and James Fadiman outline the results of a study about the potential use of psychedelics for problem solving. In the study, scientists, engineers, mathematicians, and designers took either 100 micrograms of LSD or 200mg of mescaline and worked on a problem they were personally invested in and which they had not been able to solve for at least 3 months. According to Fadiman, 9 out of 10 participants came up with a solution to the problem that was validated by the participant’s professional colleagues.

The three problems above are not easy, but they are also not insanely difficult. If it means anything to you, their level of difficulty might be around that of a problem 1 or 4 of an IMO, with the advantage that you do not need any fancy math to solve them (high-school math is more than sufficient). I do not know if solving these problems is easier or harder on psychedelics, but I figure I would share them as possible Schelling points for “challenging math problems to think about while on psychedelics” to see if anyone reports benefits from such a setup. I personally like these problems, and I can assure you that they do have interesting and clever solutions. Assuming you are already planning on taking a psychedelic substance in the future: I would recommend trying to solve one of these problems for at least 1 hour while sober, and then setting aside at least 30 minutes (preferably 1 hour) while on a psychedelic and giving it your full attention. Please let me know if you either solve the problem or get an interesting insight from such an exercise. I am particularly curious to hear about *what aspects* of the psychedelic state seemed to be either beneficial or detrimental in solving these problems. Even if you do not solve the problem, you may be able to think about it in new ways and derive useful insights. Again, if you do so, let me know as well.