DMT and Hyperbolic Geometry: 1 Million Views Special

My 2019 presentation The Hyperbolic Geometry of DMT Experiences just hit one million views on YouTube:

The casual QRI enjoyer may get the impression that this video encapsulates our current understanding of the phenomenology of DMT. The dedicated QRI reader/watcher, however, knows that we are light-years ahead in our understanding relative to where we were at the time. So I figured that this would be a good opportunity to highlight some of the DMT-specific insights that we have presented since that video came out. But before I do so, let me briefly discuss why this work is actually advancing our understanding (unlike most psychedelic phenomenology work out there) and then summarize some of the core points presented in that video so that we are all on the same page before moving on to the new models:


Introduction: What’s Useful Phenomenology?

At QRI we have put a lot of effort into characterizing what it means to describe an exotic state of consciousness in a way that is actually useful (see our guide for how to write good trip reports). Here are some key points:

Most people who try to make sense of the DMT-induced state of consciousness focus on the intentional content (the narrative) of the experience, which isn’t actually that helpful (consider how both a mescaline trip and a DMT trip can give rise to a hallucination about e.g. “meeting a dragon in another dimension”, yet the texture of such experiences will be very different!). Many others obsess over the question of whether what one experiences on DMT has a reality outside your brain or not (cf. Andrew Zuckerman has made it easy for you to test a DMT prime factorization experiment, were you to be so inclined). While interesting, I don’t think these approaches really advance our understanding very much; they in fact leave an enormous amount of low-hanging fruit uncollected.

Instead, a more fruitful approach is to focus on describing what we call the phenomenal character of the experience (yes, the dragon is important, but please also tell us how the scales on the skin of the dragon were arranged, whether they followed any wallpaper symmetry group, what their flicker frequency was, what patterns of local binding they expressed, and so on). The overwhelming majority of trip reports you can find in the literature and online don’t even try to do this. They are just quite content with a narrative account and superficial descriptions of the sensorial components of the experience (“I saw a lot of orange triangles”). But some psychonauts do try to rise to the challenge of describing the phenomenal character of the experience. Two examples are:

A step above doing this is where we find people such as Josikins (of Subjective Effect Index fame) who spend copious amounts of time trying to systematically catalogue exotic phenomenology by carefully describing and then labeling each effect with a concept handle. See also DMT-Nexus‘ systematic Hyperspace Lexicon which is perhaps a bit of a hybrid between focusing on intentional content and phenomenal character.

What’s missing here, however, is that the output ends up being a zoo of effects. Presumably, however, DMT and other psychedelics don’t have that many direct effects. Rather, they probably affect the properties of the nervous system in specific ways that in turn, downstream, give rise to a complex variety of effects. In other words, to really understand what’s going on, one should try to find a minimal set of core effects such that by combining them you get the complexity that we observe. Here is where we find people like Steven Lehar (see The Grand Illusion) and James L. Kent (see Psychedelic Information Theory). They are really experienced psychonauts who then go on to use their subject-matter expertise (cognitive science and signal processing, respectively) to explain the characteristics of the exotic states of consciousness they have experienced. They have both produced really excellent work with significant explanatory power.

At QRI we do something like that, but on a higher level. Namely, the exploration is integrated with philosophy of mind, neuroscience, and neurotechnology. What makes QRI’s psychedelic theory different than what you will see in academia is that:

  • We know of and take seriously a vastly larger experience base to work with (compared to e.g. some labs where you are not even allowed to discuss your own experiences with your colleagues!)
  • We use the framework of algorithmic reduction (and other key QRI paradigms) to try to simplify the complexity in terms of a minimal set of effects interacting with one another
  • Explore non-standard paradigms of computing (e.g. see Mike’s A Future for Neuroscience and more recently the video on Non-Linear Wave Computing), and
  • We have a crisp philosophy of mind that allows us to make modular progress on specific questions rather than being crippled by the “hard problem of consciousness” (e.g. solving the boundary problem or the translation problem can be done without having to solve everything else at once)

In other words, we actually pay attention to the details of experience no matter how weird they may be (did you know that seeing a hyperbolic honeycomb while on DMT can make your visual field “glitch”? Why does that happen?). We don’t let the theory define the facts and instead let the facts define the theory. And we try to tie it all together in light of what we know about how the nervous system works.

Example of a *structural* feature of experience: the fractal dimension of phenomenal objects. Empirically, the Hausdorff dimension of DMT phenomenal objects increases with the dose. (Ps. be careful not to look at objects with a high Hausdorff dimension while on DMT, such as cauliflowers – don’t ask me why, just don’t).


The Hyperbolic Geometry of DMT Experiences

The original article (slides; ELI5) upon which the video is based is over 8,000 words long and a lot of material is covered in it. Here I will merely highlight some of the key arguments, concepts, and talking points.

  • To a first approximation, the article does three things:
    • (1) provide detailed phenomenology focused on the structural and dynamic features that arise at each dose.
    • (2) postulate possible algorithmic reductions to explain the emergence of such structural and dynamic features.
    • (3) speculate on the information-processing properties of the state in question.
  • We point out that the reason why it is so difficult to recall the DMT experiences is that they take place in a phenomenal world with different geometry. Hence, what you do remember is whatever can exist both here and there! That said, you can modify the phenomenal objects you experienced as you come down in order to impress on them hints about what they were like up there.
  • We explain the concept of algorithmic reductions and how to apply it here.
  • Provide 17 reasons why DMT experiences are highly suggestive of hyperbolic geometry (from the presence of saddles in DMT psychedelic replications to the explicit accounts of Ralph Abraham who said his DMT experiences were distinctly non-Euclidean).
  • (1) Phenomenology:
    • Threshold (1-4mg): Crisp and high-resolution experience without obvious hallucinations. Intensified colors and sharper edges.
    • Chrysanthemum (4-8mg): The surfaces become fully saturated with wallpaper symmetry groups and then overflow, leading to a hyperbolization of such surfaces. At this level, the mind will still try to embed these constructs in 3D Euclidean space, so in practice you will see kale-like surfaces, saddles, helixes, corners, twists, etc. This often manifests as what looks like the blossoming of a flower or unwrapping of a present in the center of your attention.
    • Magic Eye (8-12mg): The Chrysanthemum becomes so curved that it can be used to render arbitrary 3D scenes of all sorts (e.g. ice cream shops, apparel, play pens, kitchen counters, etc.). We can think of this as a dynamic and animated depth map, which we call the world-sheet. If you pay attention, you will realize that the texture of the world-sheet is in fact made out of a widely contorted Chrysanthemum, with similarities to autostereograms (aka. Magic Eye visual illusions). 
    • Waiting Room (12-25mg): The curved world-sheet fully saturates 3D space; qualia continues to build to the point the that it simply does not fit 3D Euclidean space. Thus there is a forced hyperbolization of 3D phenomenal space, which also comes along a powerful multi-modal synchronization (cf. Kinesioöptic). This, in turn, makes the hallucinated world so engrossing that you lose contact with your surroundings. Often manifests as a hyper-realistic dome or series of interconnected rooms and exotic architectural structures with countless twists and turns.
    • Breakthrough (25mg+): The curvature and density of qualia is so extreme that the very topology of the worldsheet can change (e.g. via bifurcations and reconnections). One experiences radically exotic geometries of experience. There may be more than one geodesic between two given points, leading to markedly bizarre pseudo-acoustic properties. Sense of entering a sort of “interdimensional highway” that stitches together widely diverse and seemingly contradictory realities at once. (Today I would add that at this dose different regions of the experience may exhibit different pseudo-time arrows, and thus may have hybrid temporal qualities, as discussed here).
    • Amnesia (40mg+; depends): Not much to say here.
    • DMT objects, DMT space expansion, and DMT entities are described in terms of the unique features of each level.
  • (2) Algorithmic Reductions:
    • Control Interruption + Symmetry detection = Change in Metric: This algorithmic reduction combines the two core psychedelic effects of tracers (here discussed in light of Kent’s control interrupt model of psychedelic action) and lowering the symmetry detection threshold. The first one can be thought of as making the decay of qualia over time slower, and so the homeostatic level of qualia in one’s world-simulation reachers a higher level than normal. In turn, the rate at which “distances are being measured” with symmetry detection also changes. These two effects combined may give rise a network of distances between phenomenal objects that has a hyperbolic metric.
    • Dynamic System Account: Energy Sources, Sinks and Invariants: This algorithmic reduction bears a lot of similarities with predictive processing, except that it works at the algorithmic rather than computational level of abstraction.
      • We define the “Hamiltonian of Consciousness” (aka. the “temperature parameter”) as the sum total of the intensity-weighted qualia in an experience. It is noted that on DMT many energy invariants get activated: intense color can morph into acceleration which can morph into curvature and so on, as if they were trading a common currency (a unified “energy of consciousness” property).
      • Energy Sources: attention works as an energy source and on DMT this becomes intensified (almost as if the voltage of attention increased). Thus whatever you pay attention to becomes energized (brighter, faster, more curved, etc.).
      • Energy Sinks: The two main energy sinks are symmetry (not unlike how a soap bubble radiates out its energy until it settles as a perfect sphere) and semantic content (i.e. recognition). Essentially, when a part of the world-sheet starts to look symmetrical, it will “snap into symmetry” because that’s an energy minima in the neighborhood of configuration-space. And when parts of it start to resemble something you have seen or thought about before, it will snap into that configuration. We call the latter kind “Bayesian energy sinks” because they implement our perceptual priors.
      • On DMT the homeostatic balance between energy sources and sinks favors a much higher level of energy. Since curvature contributes to the Hamiltonian, most of the highly-energized states of mind are highly curved. This model wonderfully explains two aspects of tripping: first, it accounts for why what one ends up experiencing is a bizarre hybrid of symmetrical and semantic structures (e.g. faces with extra eyes, boats with point symmetry along extra degrees of freedom, etc.). And second, it explains why there are discontinuities between levels. This is because when you overwhelm the energy sinks the configuration of the world-sheet becomes less recognizable, and in turn this further blocks the ability to shed off the energy into Bayesian sinks. As a consequence, the balance between semantic content and symmetries favors symmetries on higher doses (since we lack the capacity to “recognize” semantically meaningful shapes in highly energized world-sheets).
    • Hyperbolic Micro-structure of Consciousness: This algorithmic reduction focuses on the low-level microstructure of experience. It postulates that the material properties of the world-sheet at the microscopic level are such that by energizing it one experiences a sort of thermal expansion and deformation on the parts of the world-sheet one pays attention to.
    • We note that these three algorithmic reductions might be complementary rather than mutually exclusive.
  • (3) Information Processing Properties:
    • We point out that these exotic states of consciousness may allow us to experience from the inside mathematical shapes for which mathematicians have so far had enormous difficulty visualizing and making sense of. In particular, knot complements (i.e. the space around a knot deformed so that the knot becomes the boundary at infinity), higher dimensional objects, and irreducibly complex (“prime”) shapes native to hyperbolic geometry can be encountered and interacted with. We speculate that perhaps someday breakthroughs in higher math might in fact primarily come from consciousness research centers.

Furthermore, the video includes some extra insights not present in the original article:

  • We add two more levels (which live at the interface between levels already discussed):
    • Between Threshold and Chrysanthemum there is a thin layer we call Symmetry Hotel where you still see the “real” world around you but every surface is fully saturated with wallpaper symmetry groups. Empirically, at this level the surfaces one sees on DMT can be tessellated with any of the 17 wallpaper symmetry groups and their combinations. Essentially, if you increase the energy parameter any more, then you will start to see some hyperbolization of the 2D surfaces and unlock the Chrysanthemum.
    • Between Magic Eye and Waiting Room there is a thin layer we call Crystal Worlds. It’s analogous to the Symmetry Hotel but one spatial dimension higher. Namely, the space around you becomes fully saturated with Euclidean space groups. If the energy parameter is raised any higher, then you will start to see a hyperbolization of (3D) space itself and unlock Waiting Room phenomenology.
  • In addition to the Hamiltonian of Consciousness (i.e. the temperature parameter) there is also a really important feature of experience: information content or complexity.
  • These two features define a state-space we call the Energy X Complexity landscape.
  • In order to provide an algorithmic reduction for the complexity of experience, we suggest that it is the result of feedback dynamics. This allows us to import an ontology of attractor states, which includes fixed points, limit cycles, chaos, and noise-drive spatial structures.
  • Note: In the presentation I highly recommended watching Space-Time Dynamics in Video Feedback to get a feel for this ontology. Today I would also recommend playing with the suitably psychedelic feedback-based phone app called Fraksl.
  • What defines a DMT trip is not only how far you traveled into the Energy X Complexity landscape, but also what your trajectory on it was (cf. Typical N,N-DMT Trip Progression According to an Anonymous Reader).
    • If you want to anneal a blissful state, starting in a minimally complex state and “going up” without moving right (i.e. getting caught up in any complexity) would be ideal.
    • For discovering and investigating mathematically interesting and exotic phenomena, aiming towards the upper center region would be ideal. This is where the machine elves show you absolutely mind-boggling irreducibly complex synesthetic patterns of qualia for which we have no names.
    • For processing stored inner tension or trauma, it might be necessary to go to the middle right region in order to induce entropic disintegration of patterns and then come back via the low-complexity region to anneal a harmonious state.
  • We concluded the presentation by suggesting that a way forward for science to investigate DMT-like states of consciousness would be to plan legal retreats with physicists, mathematicians, electrical engineers, and visual artists so that the models here presented could be explored, tested, and further developed out in the open.

More Recent DMT Insights

The descriptions shown below merely scratch the surface. Think of them as pointers rather than the insights themselves. For the videos in particular, even if you don’t have the time to see them in full, I nonetheless recommend clicking on them and reading their descriptions (rather than merely the excerpts pasted below). Of course there really isn’t a good substitute for watching the entire video if you want the detailed explanation.

  • November 15, 2019 Break Out of the Simulation Day: Televised Entity Contact, Injection Pulling Experiments, and the Brain as a Game Engine (article)
    • This essay proposes a novel way of testing the independent reality of DMT entities: one could in principle determine that the brain state is being influenced by an external force by looking for the dynamic signatures of injection pulling in neuroimaging data.
  • July 1, 2020 5-MeO-DMT vs. N,N-DMT: The 9 Lenses (article)
    • This article describes 9 key differences between the phenomenology of DMT and 5-MeO-DMT: (1) Space vs. Form: 5-MeO is more space-like than DMT. (2) Crystals vs. Quasi-Crystals: 5-MeO generates more perfectly repeating rhythms and hallucinations than DMT. (3) Non-Attachment vs. Attachment: 5-MeO seems to enable detachment from the craving of both existence and non-existence, whereas DMT enhances the craving. (4) Underfitting vs. Overfitting: 5-MeO reduces one’s model complexity whereas DMT radically increases it. (5) Fixed Points and Limit Cycles vs. Chaotic Attractors: 5-MeO’s effect on feedback leads to stable and predictable attractors while DMT’s attractors are inherently chaotic. (6) Modulation of Lateral Inhibition: 5-MeO may reduce lateral inhibition while DMT may enhance it. (7) Diffuse Attention vs. Focused Attention: 5-MeO diffuses attention uniformly over large regions of one’s experiential field, while DMT seems to focus it. (8) Big Chunks and Tiny Chunks vs. A Power Law of Chunks: 5-MeO creates a few huge phases of experience (as in phases of matter) with a few remaining specks, while DMT produces a more organic power law distribution of chunk sizes. (9) Integration vs. Fragmentation: 5-MeO seems to give rise to “neural integration” involving the entrainment of any two arbitrary subnetworks (even when they usually do not talk to each other), while DMT fragments communication between most networks but massively enhances it between some specific kinds of networks.
  • October 9, 2020 Modeling Psychedelic Tracers with QRI’s Psychophysics Toolkit: The Tracer Replication Tool (article)
    • This is the first attempt at quantitatively and qualitatively measuring the tracer characteristics of DMT hallucinations (try it yourself!). Preliminary findings suggest that DMT is special relative to other psychedelics in the following ways. First, it has pronounced tracer effects. Second, they flicker at a much higher frequency than other drugs (~30 Hz relative to ~15-20 for LSD and ~12 for 2C-B). Third, there are both strobe and replay effects galore. Fourth, there is a color pulsing effect at a very high frequency (also around 30 Hz). Unlike 5-MeO-DMT, which gives rise to monochromatic tracers, on DMT the color of the tracers alternates between their positive and negative afterimages.
  • Jan 8, 2021 Why Does DMT Feel So Real? Multi-modal Coherence, High Temperature Parameter, Tactile Hallucinations (video essay)
    • This explains why it is so hard to not take at face value the reality of the hallucinations on DMT. When we take psychedelics, we learn what “channels” of information become distorted and which ones can be trusted. It turns out that DMT can mess with many more channels relative to other psychedelics (such as LSD, mescaline, or 2C-B). In particular, DMT is exceptional in the degree of (1) cross-modal coherence that it induces, (2) heat, giving rise to a very high temperature parameter of experience, and (3) realistic tactile hallucinations. These three features combined might go a long way in explaining why DMT feels so real. Namely, that you can experience detailed tactile feelings like “crossing a veil” or “being invaded by energetic bugs” or “being operated on” that are coherent with the information you are receiving from other senses and are felt with a level of intensity much greater than the feelings one is used to in everyday life. This synergizes to create a very realistic feeling of touching parallel realities.
  • Feb 15, 2021 A Language for Psychedelic Experiences: Algorithmic Reductions, Field Operators, and Dimensionality (video essay)
    • From the description: We suggest that a remarkably fruitful strategy for pointing at a whole family of psychedelic effects comes in the form of “field operators” that change the qualitative properties of our experiential fields. I provide a detailed description of what we call the “world-sheet” of experience and how it encodes emotional and semantic content in its very structure. The world-sheet can have tension, relaxation, different types of resonance and buzzing entrainment, twisting, curling, divergence (with vortices and anti-vortices in the attention field-lines), dissonance, consonance, noise, release, curvature, holographic properties, and dimensionality. I explain that in a psychedelic state, you explore higher up regions in the “Hamiltonian of the field”, meaning that you instantiate field configurations with higher levels of energy. There, we observer interesting trade-offs between the hyperbolicity of the field and its dimensionality. It can instantiate fractals of many sorts (in polar, cartesian, and other coordinate systems) by multi-scale entrainment. Time loops and moments of eternity result from this process iterated over all sensory modalities. The field contains meta-data implicitly encoded in its periphery which you can use for tacit information processing. Semantic content and preferences are encoded in terms of the patterns of attraction and repulsion of the attention-field lines.
  • May 8, 2021 Healing Trauma with Neural Annealing (article & presentation)
    • This writeup does a lot of things. While the focus is on application (i.e. how to heal trauma with psychedelics), it also lays out a very significant amount of novel psychedelic theory. Excerpt: A lot of psychedelic phenomenology suggests that there is a duality between the vibe of the state and the geometric layout of the multi-modal hallucinations. In other words, each phenomenal object has a corresponding way of vibrating, and this is experienced as a holistic signature of such objects. (cf. Resonance and vibration of [phenomenal] objects). (See also: Hearing the shape of a drum). In the context of this presentation, the most important idea of this slide is that the duality between standing wave patterns and the vibe of the experience showcases how symmetry and valence are related. Blissful “heavenly realms” on DMT are constructed in ways where the resonance of the phenomenal objects with each other is consonant and their structure is symmetrical. Likewise, the screechy and painful quality of the DMT “hell realms” comes along with asymmetries, discontinuities, and missing components in the phenomenal objects that make up experiences. The overall vibe of the space is the result of the intrinsic vibratory modes of each phenomenal object in addition to each of the possible interactions between them (weighted by their phenomenal distance). An analogy readily comes to mind of an orchestra and the challenges that come with making it sound consonant. […] We hypothesize that DMT’s effects at the implementation level can be understood as the result of competing clusters of coherence across the hierarchy, whereas the main attractors of 5-MeO-DMT seem to involve global coherence. Modulating the average synaptic path length in a system of coupled oscillators can give rise to this sort of effect. By randomly adding connections to a network of coupled oscillators one first sees an emergent state of many competing patches of synchrony, and then, after a threshold is crossed, one starts seeing global synchrony emerge. Despite both drugs making the brain “more interconnected”, the slight difference in just how interconnected it makes it, may be the difference between the colorful chaos of DMT and the peaceful nothingness of 5-MeO-DMT. The competing clusters of coherence across the hierarchy can evolve to adapt to each other. The DMT realm is more of an ecosystem than it is a state per se (ex: Hyperspace Lexicon). And due to the duality between dissonance minimization and prediction error minimization, avoiding updating one’s belief in the direction of these realms being real causes intense cognitive dissonance. Some level of belief updating to fit the content of the hallucinations might be very difficult to resist. Indeed, the forced coherence across the layers of the hierarchy would be bypassing one’s normal ability to resist information coming from the lower layers.
      As you can see, contrary to what many people in the comments* seem to say, DMT visuals are in fact extremely important and not at all just a superficial aspect of the experience. Due to the duality between the vibe of the state and the geometric layout of the multi-modal hallucinations, it is always the case that the geometry of your experience will be a reflection of your emotional processing! Solving for harmony in your hallucinations will in turn have unexpected harmonizing effects at the emotional level as well.
  • May 31, 2021 DMT vs. 5-MeO-DMT: 12 Key Differences (video essay)
    • This video essay expands on the article and adds three key differences: (10) Global Coherence vs. Competing Clusters of Coherence: 5-MeO-DMT gives rise to a global coherent state (the so-called “unified energy field”), whereas DMT gives rise to an ecosystem of time-loops, each trying to capture as much of your attention as possible, which in turn results in coalition-building and evolution of patterns in the direction of being very “attention grabbing” (cf. reddit.com/r/place). (11) Really Positive or Really Negative Valence vs. Highly-Mixed Valence: 5-MeO-DMT gives rise to either a globally coherent state (high-valence) or two competing coherent states (negative-valence), whereas DMT tends to generate complex consonance/dissonance relationships between the clusters of coherence. (12) How they are different according the the Free Energy Principle: On 5-MeO-DMT the entire experience has to reinforce itself, whereas each cluster of coherence needs to model the rest of the experience in order to be reinforced by it on DMT. Thus 5-MeO-DMT makes experiences that express “the whole as the whole” whereas DMT makes each part of the experience represent the whole yet remains distinct.
  • Jun 20, 2021 Psychedelics and the Free Energy Principle: From REBUS to Indra’s Net (video essay)
    • The key achievement of this video is to discuss the Free Energy Principle and Predictive Processing at the implementation level of analysis in light of Neural Annealing, the Symmetry Theory of Valence, and Holistic Field Behavior. Here we realize that prediction errors feel bad not because they are inherently negative, but because the nervous system is implemented in such a way that they generate dissonance. More so, there is also a dissonance cost to model complexity (complex internal representations “self-intersect” and thus generate dissonance). This balances out so that our nervous system minimizing dissonance ends up generating relatively simple models with high levels of accuracy. In other words, it avoids both underfitting and overfitting merely by trying to minimize internal dissonance! The video also articulates how Bayesian Energy Sinks might be implemented. It concludes with a derivation of the “mystical” (or psychedelic, really) state of Indra’s Net, i.e. why on substances such as DMT it often feels like “everything reflects everything else”. Indra’s Net, it turns out, can be explained as a local energy minima of a highly energized system of coupled oscillators organized hierarchically so that each “competing cluster of coherence” minimizes its energy by predicting perfectly the behavior of the surrounding ones. In other words, each “competing cluster of coherence” needs to model its environment in order to synch up with it in a reinforcing way. This leads to attractor states where everything is a reflection of everything else.
  • Sep 24, 2021 Are Higher Dimensions Real? From Numerology to Precision Xenovalence – 4 5 6 8 10 12 16 20 24 32 (video essay)
    • This video explains how a system of coupled oscillators can in fact instantiate virtual higher dimensions. Namely, dynamic systems that behave as if they were embedded in a higher spatial dimension. There is a trade-off between degrees of freedom and higher virtual dimensions. It argues that indeed on DMT one can experience such higher dimensions and that in light of the Symmetry Theory of Valence there is a corresponding “generalized music theory” that explains why some of them feel good and others not. Additionally, there seems to be an algebra for how “DMT objects” with specific dimensionalities can be composed with one another (the 2D symmetry slabs found in Symmetry Hotel can be composed with each other to form 3D spatial structures native to the Crystal World level).
  • Jan 30, 2022 Qualia Computing: How Conscious States Are Used For Efficient And Non-Trivial Information Processing (video essay)
    • From the video description: The reason we are conscious is because being conscious allows you to recruit self-organizing principles that can run on a massively parallel fashion in order to find solutions to problems at [wave propagation] speed. Importantly, this predicts it’s possible to use e.g. a visual field on DMT in order to quickly find the “energy minima” of a physical state that has been properly calibrated to correspond to the dynamics of a world-sheet in that state. This is falsifiable and exciting.
  • Feb 26, 2022 Full-Spectrum Superintelligence: From Shape Rotator to Benevolent Rainbow God
    • From the video description: High-octane mental power, when pointed in a pointless direction, is not particularly useful. Thus, we must enrich our conception of intelligence to encapsulate philosophical, meditative, and existential cognition. And, perhaps the Crown Jewel of Intelligence: the ability to explore, make sense of, navigate, and recruit exotic states of consciousness for information processing and aesthetic purposes. In particular, I make the case that intelligence is truly about identifying *self-organizing principles* of physics that are energetically cheap which can *solve the problem for you* (cf. “Repulsive Shape Optimization”).
  • Mar 5, 2022 Non-Linear Wave Computing: Vibes, Gestalts, and Realms (video essay)
    • DMT both energizes one’s state of consciousness and also provides a new medium of wave propagation. At a sufficient dose (>5mg) it takes one’s consciousness to the non-linear regime. This video discusses the very nature of vibes, how gestalts arise, and how they assemble to form realms. It also explains how a vibe acquires its valence (partly through its ADSR envelope characteristics). If you only watch one video, make it this one.
  • Mar 15, 2022 Attention & Awareness: Oscillatory Complementarity, Non-Linearities, and the Pointlessness of It All (video essay)
    • This video explains how DMT objects emerge out of exotic attention-awareness patterns. From the video description: LSD non-duality can be understood as more diffuse elements of experience becoming the non-linear oscillatory complements of the field of awareness, such as “light”, “space”, and “being”. DMT’s competing clusters of coherence and their compositional properties also emerge naturally out of a hyper-energized field of awareness that generates oscillatory complements. 5-MeO-DMT is a straight path to insight territory, as it activates a new medium of wave-propagation orthogonal to the one in which our world-simulation is typically embedded. And so on… I also re-evaluate the models introduced in the original Qualia Computing article on the geometry of DMT experiences in light of this new paradigm. In particular, I delve into the concept of exotic attention in the form of wallpaper symmetry groups and Bayesian energy sinks.

DMT-related Media Appearances

Since the Harvard presentation, I have also given many other presentations and participated in podcasts, some of which touch upon DMT. Here is a selection of some of the most relevant ones:


Note: Of course all of this still needs to be synthesized, presented, and written up in ways that can interface more smoothly with academia and the world at large. That said, I constantly get emails and messages from people in academia (typically PhD students, but often also professors and even heads of labs) telling me that QRI’s psychedelic theory is the most illuminating content they are aware of when it comes to how to make sense of exotic states of consciousness. One relatively well-known academic described our models in private as “two steps ahead of the current understanding in academia”. Sadly, I am also aware of a few peer reviewed articles and publications that present our ideas as their own- ideas which we shared with the authors in private meetings, where they told us they were insightful and new to them at the time. I would kindly request to any academic reader of QRI to please cite our articles and videos if they inspired or informed their research in any way. It’s of course a matter of intellectual integrity to do so (and contrary to common misconception, you can in fact cite blogposts and YouTube videos in your scientific articles! In fact, not doing so when you got a key insight from them goes against the very spirit of science. Please do so when appropriate). Thank you, and remember that citing us for our meaningful contributions to the field will put a smile on my face! 🙂

(source)


Special thanks to: Everyone at QRI (especially Michael Johnson, for years of fruitful collaboration on these topics). Andrew Zuckerman and Kenneth Shinozuka who were instrumental for setting up this presentation and so many other things. Quintin Frerichs who 3D-printed and brought the cool shapes shown in the video**, not to speak of his outstanding internal technical contributions. Romeo Stevens for all the incredible support (he was also there in the audience!). Anders Amelin and Maggie Wassinge for their brilliant and holistic contributions to the conversation. Marcin Kowrygo and Hunter Meyer for stepping up in times of need and being such great and dedicated helpers in so many ways. The extended QRI network and anonymous psychonauts who have participated in fruitful discussions and informed our models. David Pearce for years of friendship and collaboration in this and related areas. Our donors for bravely supporting our projects despite how crazy they may seem from the outside view. And to YOU, dear reader. Thank you all!

Infinite bliss!


* You can find my response to the most common kinds of comments on the video here: Collecting Qualia Souvenirs.

**They are technically {5,3,4} hyperbolic honeycombs drawn in the Poincaré ball model. We got the files from Henry Segerman‘s website.

High Valence 5-MeO-DMT + Nitrous Oxide Trip Report from an Anonymous Reader

Here’s an interesting report I received a few days ago. It’s noteworthy due to the author’s familiarity with QRI paradigms, emphasis on the phenomenal character rather than on the intentional content of the experience, and its interest in observing the structural properties of valence. [Comments and links added by me].

25/03/2021 – Conversations with my ‘self’ and cheat codes to bliss

Demographic information:

Age: 24
Gender: Male
Ethnicity: European descent
Weight: 70-75kg
Height: 170-180cm

Substances consumed:

T- 1:30 45g raw cacao (solid) [NOTE: it’s unsafe to combine 5-MeO-DMT and MAOIs. I do not know if cacao’s MAOIs in these doses could possibly represent a problem, but out of an abundance of caution I’d recommend against it.]
T+/- 0:00 ~30mg(?) 5-MeO-DMT (freebase)
T+ 0:25-1:30 13 double balloons of nitrous oxide
T+ 0:35 ~50mg cannabis

Set and setting:

I prepared my room by cleaning the air with my HEPA purifier, increasing the temperature to a comfortable degree, turning off all the lights (except for a dull red light in the corner), and collecting various soft blankets and pillows into a heap on my bed.

I prepared my mind by drinking cacao, re-reading some of my favourite 5-MeO-DMT trip reports and accounts of its phenomenology, and meditating for 20 minutes.

Past experiences:

Two past experiences with 5-MeO-DMT at low doses:

  1. A dose of 10-15mg (plugged) in which I experienced ~45 minutes of very slight effects. Around 15 minutes into the experience I decided to experiment with nitrous oxide, which I discovered increased the feeling of connectedness and bliss considerably, but still not to the level of combining high doses of other drugs with nitrous. Around 30 minutes into the experience and past the ‘peak’ I vaporised a small amount of cannabis, which brought back the intensity of the 5-MeO-DMT for a brief period (~10 mins) in conjunction with the nitrous.
  2. A dose of ~5mg (vaporised) to test ‘the machine’ pipe that I built. The energy / intensity I felt was perhaps 5 times greater than my past experience with 5-MeO-DMT (not counting the nitrous and cannabis synergy), but only lasted for about 10 minutes.

Two past experiences of N,N-DMT at low doses:

  1. A mild dose of ayahuasca.
  2. A moderate dose of changa (to the ‘Magic Eye Level’).

Lots of experience (~50+) with conventional psychedelics (e.g., LSD, Mescaline, Psilocybin, 2C-B), often mixed with other psychoactive compounds (e.g., cannabis, ketamine, MDMA, nitrous oxide, Syrian rue).

Philosophical background:

I have studied analytic philosophy near full-time for the past eight years with a focus on philosophy of mind, philosophy of biology, applied ethics, well-being, and value theory. During this time, I have developed a strong personal ontology of experientialism (i.e., subjective experiences are important to answering philosophical questions in a fundamental rather than instrumental sense).

I have actively followed LessWrong & its blogging community for the past three years, and first encountered QRI and Qualia Computing approximately two years ago. For the past year, perhaps 70-80% of my recreational research consumption has consisted of QRI content or adjacent material. I broadly agree with QRI paradigms – in particular, the notion that the best way to understand subjective experiences involves analyzing their structural rather than representational content. About three months ago, I also converted from empty individualism to open individualism.

Phenomenology report:

I was gifted about ~40mg of 5-MeO-DMT from a friend. Unfortunately, they did not weigh it out, nor do I have a precision scale, so the actual quantity of the substance I received could have been +/- 10mg from the estimated quantity.1 I had already used one quarter of this amount (10mg) to test my vaporisation apparatus, of which I wasted half (5mg), so I assumed that I had 30mg left. After talking with some friends and weighing up the risks, I decided that I would try to vaporise the remaining quantity in one go. I strongly discourage anybody reading this report from being so reckless; my rationale was that (1) I have limited access to 5-MeO-DMT and I did not want to waste this rare opportunity, (2) I have extensively researched the phenomenology of 5-MeO-DMT consumption and knew what to expect, and (3) my prior on having a ‘bad trip’ on conventional psychedelics is very low.2

Earlier in the evening I consumed 45g of raw cacao, which I grated up and boiled in a small pot of soy milk (with monk fruit extract added to sweeten the mix). The subjective effects of unprocessed cacao at high doses are very slight and similar to coffee (probably due to its mild caffeine content), but with more of an empathetic and euphoric quality. That said, I suspect that an individual’s expectations also play a nontrivial role in producing these effects.

After preparing my room and meditating for a short period to lower my heart rate (which I measured using a pulse oximeter), I fired up ‘the machine’. Due to the small size of the device, the chamber filled up fairly quickly and I lost some vapor, so after about 20 seconds I began to slowly inhale the contents of the chamber while continuing to heat the steel mesh with my butane torch. Soon enough I began to feel the effects of the substance, and once I lost the ability to coordinate my hands I placed the device gently on my bed, wrapped myself up in a soft blanket, and lay down with my eyes closed. In the background, I had the song ‘Structures from Silence’ by Steve Roach playing quietly.

My memories of the peak are very limited, and that is because I lost the capacity to experience the passing of time, the boundaries of space, and even the first-person phenomenology of thought. While I have had psychedelic experiences resembling descriptions of ego death before, I don’t believe that I have ever had an experience in which my attention – the focussing of my awareness on particular aspects of my experience – was entirely absent from my consciousness. Without this capacity, the appearance of duality within my experience collapsed, such as the distinction between subject and object, internal and external, or mind and body. This corresponds with nondual accounts of 5-MeO-DMT that I have previously read where people experience ‘becoming one with the universe’ or ‘pure consciousness’.

An important takeaway from this trip was that while the valence of the experience was very high, it felt qualitatively different from ordinary instances of high valence experiences, such as physical pleasure. If I had to describe the general qualia of being on 5-MeO-DMT, I would use the terms ‘significant’ or ‘meaningful’ rather than ‘good’ or ‘enjoyable’ [see a similar observation made on this trip report]. Consider the feeling of encountering something so profoundly important that it cuts deep into your conception of intrinsic value, and then increase the intensity of that feeling by a few orders of magnitude. However, I could not point out where in my field of experience the feeling of ‘significance’ was located, suggesting global rather than local coherence.3 Additionally, while the information content of the experience was extremely low, the feeling of ‘connectedness’ was extremely high.4 I remember observing this as I was coming up and coming down from the peak – the perception of ‘synchrony’ between different modes of my experience directly mapped onto its perceived intensity.

After I had regained my attention, the first thing I noticed within my body was how heavily I was breathing – louder and faster than if I had just finished a sprint [I don’t know how common this is, and/or if it might be related to the cacao consumed before the experience]. From past experiences of ego-disillusion, I know that once I have passed an energy threshold my nervous system will instantiate a ‘self-preservation’ algorithm which involves breathing heavily. Soon after noticing this, I became aware that I was on 5-MeO-DMT and so I was not alarmed. My body then began to cry; however, as my consciousness was still experiencing disembodiment, ‘I’ did not identify with the crying state and simply observed this process as it unfolded.

After a short period, my body rolled over onto its front and began talking sweetly to ‘me’ – the disembodied awareness – as if different aspects of my internal personality model wanted to reassure the light of consciousness trapped within that it was loved and supported, and to thank it for always being there to assist in the survival of the organism that sustained us both. This was totally fascinating to experience, especially as I became increasingly lucid until eventually it was ‘me’ who was talking! In other words, I experienced a gradual merging of two distinct ‘selves’ – the metaphysical ‘me’ (i.e., my conscious awareness) with the ontological ‘me’ (i.e., my ‘self’ model) – until one had completely osmosed into the other and an equilibrium was reached. I feel very fortunate to hold a system of philosophical beliefs that is sophisticated enough to make sense of this experience without detracting from its perceived significance. Also, yay to self-love! <3

Immediately after this ‘cool down’ period, I decided to try and use up whatever was left within the vaporisation device, which turned out to be quite a lot!5 I’d say that while I didn’t go into ‘blackout’ territory, I certainly re-entered nonduality, and soon enough experienced my self-model talking to my consciousness again. I then decided to experiment with potential synergies between 5-MeO-DMT and other psychoactive substances I had lying around in order to document their effects. Given the success of my past experience on a very low dose of 5-MeO-DMT (plugged) and nitrous oxide, I cracked two bulbs into my nitrous canister, prepared as much 5-MeO-DMT as I had left in the glass device and inhaled it, and then quickly discharged the pressurised gas into a large balloon which I subsequently inhaled, repeating this process several times.

The resulting experience was, somewhat surprisingly, higher valence than my 5-MeO-DMT breakthrough.6 On its own, nitrous isn’t that interesting to experience, but it has remarkable synergistic properties when combined with other drugs – especially psychedelics. It is difficult to describe the exact ways in which the phenomenology of nitrous interacts with the phenomenology of 5-MeO-DMT, but I can confidently say that the valence I experienced was more blissful / pleasurable but less spiritually significant. In a general sense, I would argue that nitrous functions as a sort of magnifying glass on certain aspects of experience by slowing down the speed at which your consciousness processes sensory information (which includes thought), and in this specific case it amplified the blissful qualia that resulted from having high levels of consonance between different regions of my nervous system. I also noticed that if I wrapped myself in my softest blanket immediately after inhaling the nitrous and consciously wriggled my body around, the tactile sensations gave me my first visuals; tens of thousands of tiny specs of qualia dotted across my world-sheet, moving together in a synchronous pattern corresponding to the feeling of soft fabric rubbing against my skin.

After vaporising absolutely everything in the glass chamber, I then proceeded to vaporise some cannabis to observe how it would interact with the residual effects of the 5-MeO-DMT that still remained in my body. The resulting effects were then more typical of ordinary nitrous experiences, except that they were far more tranquil with a deeper sense of love, compassion, and serenity. During the peak of each balloon, I had the first-person sense of ‘being’ a thought process, constructing low-information ontological models that entirely made up my world simulation. Coming out of each balloon involved constantly updating this ontological model to account for a steady flow of prediction errors as I was increasingly capable of comprehending complexity within patterns of information contained within my experience, until I would eventually realise that I had taken nitrous.7

Concluding remarks:

I would like to reiterate that guesstimating the dose of a highly volatile and dose-dependent drug such as 5-MeO-DMT is extremely dangerous – especially without taking steps to work your way up the dosage ladder to become acquainted with its effects. As such, I would not recommend doing what I did for the vast majority of people interested in taking 5-MeO-DMT. Despite this risk, I had what was probably the most intense experience of my life and it was net-positive in valence, so I consider it a success. I am looking forward to future experimentation with this substance – especially in conjunction with nitrous oxide – and would like to work on developing a better understanding of how nitrous works and why it produces such a wide range of effects with different drug cocktails.8

Notes:

1. I do not endorse eyeballing drug doses – especially high-energy substances such as 5-MeO-DMT that have the potential to create extremely unpleasant states of consciousness. [This is such an important point that I considered not sharing this report based on this fact alone in order to not encourage unsafe practices. In the end I figured that the content was valuable enough that sharing it with this note was worth it nonetheless. The point remains: NEVER eyeball milligram-sensitive drugs like 5-MeO-DMT.]

2. This observation is based on past experiences in which I have consumed high doses of psychedelics – often in conjunction with other substances – and observed the various autonomic responses of my body and mind.

3. This is not the case with ordinary high valence experiences in which I can usually locate its ‘source’ within specific sensations (e.g., tactile, visual, auditory).

4. I cannot remember whether I opened my eyes, but I’m sure even that if I did, this would not have altered any aspect of the experience in the moment.

5. I hypothesized that it would be more efficient to use the remaining 5-MeO-DMT as soon as I could physically operate the device in order to make use of the residual effects of the previous dose that I had consumed.

6. Perhaps this is more the result of my having extensive experience with nitrous and limited experience with 5-MeO-DMT, or my 5-MeO-DMT experience was more mixed / dissonant than I remember.

7. For some, the vibe of nitrous can be quite frightening, as if they are the subject of one big cosmic joke. However, for the philosophically minded who are also on the right combination of substances, it can be an extremely intellectually rewarding experience, shedding light on the internal workings of their mind.

8. A combination I am even more excited to experiment with is MDMA + 5-MeO-DMT + Nitrous Oxide, which I would assign a nontrivial chance to being the most blissful synergy between all known substances.


Featured image by: Marek Piwnicki on Unsplash


See other high-quality trip reports:

Also relevant:

7 Recent Videos: Cognitive Sovereignty, Phenomenology of Scent, Solution to the Problem of Other Minds, Novel Qualia Research Methods, Higher Dimensions, Solution to the Binding Problem, and Qualia Computing

[Context: 4th in a series of 7-video packages. See the previous three packages: 1st2nd, and 3rd]


Genuinely new thoughts are actually very rare. Why is that? And how can we incentivize the good side of smart people to focus their energies on having genuinely new thoughts for the benefit of all? In order to create the conditions for that we need to strike the right balance between many complementary forces.

I offer a new ideal we call “Cognitive Sovereignty”. This ideal consists of three principles working together in synergy: (1) Freedom of Thought and Feeling, (2) Idea Ownership, and (3) Information Responsibility.

(1) Freedom of Thought and Feeling is the cultivation of a child-like wonder and positive attitude towards the ideas of one another. A “Yes And” approach to idea sharing.

As QRI advisors Anders Amelin and Margareta “Maggie” Wassinge write on the topic:

“On the topic of liberty of mind, we may reflect that inhibitory mechanisms are typically strong within groups of people. As is the case within minds of individuals. In minds it’s this tip of the iceberg which gets rendered as qualia and is the end result of unexperienced hierarchies of powerfully constraining filters. It’s really practical for life forms to function this way and for teams made up of life forms to function similarly, but for making grand improvements to the very foundations of life itself, you need maximum creativity instead of the default self-organizing consensus emergence.

“There is creativity-limiting pressure to conform to ‘correctness’ everywhere. Paradigmatic correctness in science, corporate correctness in business, social correctness, political correctness, and so on. As antidotes to chaos these can serve a purpose but for exceptional intellectual work to blossom they are quite counterproductive. There is something to be said for Elon Musk’s assertion that ‘excellence is the only passing grade’.

“The difference to the future wellbeing of sentient entities between the QRI becoming something pretty much overall OK-ish, and the QRI becoming something of great excellence, is probably bigger than between the corresponding outcomes for Tesla Motors.

“The creativity of the team is down to this exact thing: The qualia computing of the gut feeling getting to enjoy a haven of liberty all too rare elsewhere.”

On (2) we can say that to “be the adult in the room” is also equally important. As Michael Johnson puts it, “it’s important to keep track of the metadata of ideas.” One cannot incentivize smart people to share ideas if they don’t feel like others will recognize who came up with them. While not everyone pays close attention to who says what in conversation, we think that a reasonable level of attention on this is necessary to align incentives. Obviously too much emphasis on Idea Ownership can be stifling and generate excessive overhead. So having open conversations about (failed) attribution while assuming the best from others is also a key practice to make Idea Ownership good for everyone.

And finally, (3) is the principle of “Information Responsibility”. This is the “wise old person” energy and attitude that deeply cares about the effects that information has on the world. Simple heuristics like “information wants to be free” and the ideal of a fully “open science” are pleasant to think about, but in practice they may lead to disasters on a grand scale. From gain of function research in virology to analysis of water pipes in cities, cutting-edge research can at times encounter novel ways of causing great harm. It’s imperative that one resists the urge to share them with the world for the sake of signaling how smart one is (which is the default path for the vast majority of people and institutions!). One needs to cultivate the wisdom to consider the long-term vision and only share ideas one knows are safe for the world. Here, of course, we need a balance: too much emphasis on information security can be a tactic to thwart other’s work and may be undully onerous and stifling. Striking the right balance is the goal.

The full synergy between these three principles of Cognitive Sovereignty, I think, is what allows people to think new thoughts.

I also cover two new key ideas: (a) Canceling Paradise and (b) Multi-level Selection and how it interacts with Organizational Freedom.

~Qualia of the Day: Long Walks on the Beach~

Relevant links:


In this talk we analyze the perfume category called “Aromatic Fougère” in order to illustrate the aesthetic of “Qualiacore” in its myriad manifestations.

Definition: The Qualiacore Aesthetic is the practice and aspiration to describe experiences in new, meaningful, and non-trivial ways that are illuminating for our understanding of the nature of consciousness.

At a high-level, we must note that the classic ways of describing the phenomenology of scents tend to “miss the target”. Learning about the history, cultural imports, associations, and similarities between perfumes can be fun to do but it does not advance an accurate phenomenological impression of what it is that we are talking about. And while reading about the “perfume notes” of a composition can place it in a certain location relative to other perfumes, such note descriptions usually give you a false sense of understanding and familiarity far removed from the complex subtleties of the state-space of scent. So how can we say new, meaningful, and non-trivial things about a smell?

Note-wise, Aromatic Fougères are typically described as the combination of herbs and spices (the aromatic part) with the core Fougère accord of oak moss, lavender/bergamot, geranium, and coumarin. In this video I offer a qualiacore-style analysis of how these “notes” interact with one another in order to form emergent gestalts. Here we will focus on the phenomenal character of these effects with an emphasis on bringing analogies from dynamic system behavior and energy-management techniques within the purview of the Symmetry Theory of Valence.

In the end, we arrive at a phenomenological fingerprint that cashes out in a comparison to the psychoactive effect of “Calvin Klein” (cocaine + ketamine*), which blends both stimulation and dissociation at the same time – a rather interesting effect that can be used to help you overcome awkwardness barriers in everyday life. “Smooth out the awkwardness landscape with Drakkar Noir!”

I also discuss the art of perfumery in light of QRI’s 8 models of art:

  1. Art as family resemblance (Semantic Deflation)
  2. Art as Signaling (Cool Kid Theory)
  3. Art as Schelling-point creation (a few Hipster-theoretical considerations)
  4. Art as cultivating sacred experiences (self-transcendence and highest values)
  5. Art as exploring the state-space of consciousness (ϡ☀♘🏳️‍🌈♬♠ヅ)
  6. Art as something that messes with the energy parameter of your mind (ꙮ)
  7. Art as puzzling valence effects (emotional salience and annealing as key ingredients)
  8. Art as a system of affective communication: a protolanguage to communicate information about worthwhile qualia (which culminates in Harmonic Society).

~Qualia of the Day: Aromatic Fougères~

* Extremely ill-advised.

Relevant links:


How do you know for sure that other people (and non-human animals) are conscious?

The so-called “problem of other minds” asks us to consider whether we truly have any solid basis for believing that “we are not alone”. In this talk I provide a new, meaningful, and non-trivial solution to the problem of other minds using a combination of mindmelding and phenomenal puzzles in the right sequence such that one can gain confidence that others are indeed “solving problems with qualia computing” and in turn infer that they are independently conscious.

This explanatory style contrasts with typical “solutions” to the problem of other minds that focus on either historical, behavioral, or algorithmic similarities between oneself and others (e.g. “passing a Turing test”). Here we explore what the space of possible solutions looks like and show that qualia formalism can be a key to unlock new kinds of understanding currently out of reach within the prevailing paradigms in philosophy of mind. But even with qualia formalism, the radical skeptic solipsist will not be convinced. Direct experience and “proof” is necessary to convince a hardcore solipsist since intellectual “inferential” arguments can always be mere “figments of one’s own imagination”. We thus explore how mindmelding can greatly increase our certainty of other’s consciousness. However, skeptical worries may still linger: how do you know that the source of consciousness during mindmelding is not your brain alone? How do you know that the other brain is conscious while you are not connected to it? We thus introduce “phenomenal puzzles” into the picture: these are puzzles that require the use of “qualia comparisons” to be solved. In conjunction with a specific mindmelding information sharing protocol, such phenomenal puzzles can, we argue, actually fully address the problem of other minds in ways even strong skeptics will be satisfied with. You be the judge! 🙂

~Qualia of the Day: Wire Puzzles~

Many thanks to: Everyone who has encouraged the development of the field of qualia research over the years. David Pearce for encouraging me to actually write out my thoughts and share them online, Michael Johnson for our multi-year deep collaboration at QRI, and Murphy-Shigematsu for pushing me over the edge to start working on “what I had been putting off” back in 2014 (which was the trigger to actually write the first Qualia Computing post). In addition, I’d like to thank everyone at the Stanford Transhumanist Association for encouraging me so much over the years (Faust, Karl, Juan-Carlos, Blue, Todor, Keetan, Alan, etc.). Duncan Wilson for the beautiful times discussing these matters. Romeo Stevens for the amazing vibes and high-level thoughts. And of course everyone at QRI, especially Quintin Frerichs, Andrew Zuckerman, Anders and Maggie, and the list goes on (Mackenzie, Sean, Hunter, Elin, Wendi, etc.). Likewise, everyone at Qualia Computing Networking (the closed facebook group where we discuss a lot of these ideas), our advisors, donors, readers, and of course those watching these videos. Much love to all of you!

Relevant links:

“Tout comprendre, c’est tout pardonner” – To understand all is to forgive all.


New scientific paradigms essentially begin life as conspiracy theories, noticing the inconsistencies the previous paradigm is suppressing. Early adopters undergo a process that Kuhn likens to religious deconversion.” – Romeo Stevens

The field of consciousness research lacks a credible synthesis of what we already know about the mind. One key thing that is holding back the science of consciousness is that it’s currently missing an adequate set of methods to “take seriously” the implications of exotic states of consciousness. Imagine a physicist saying that “there is nothing about water that we can learn from studying ice”. Silly as it may be, the truth is that this is the typical attitude about exotic consciousness in modern neuroscience. And even with the ongoing resurgence of scientific interest in psychedelics, outside of QRI and Ingram’s EPRC there is no real serious attempt at mapping the state-space of consciousness in detail. This is to a large extent because we lack the vocabulary, tools, concepts, and focus at a paradigmatic level to do so. But a new paradigm is arriving, and the following 8 new research methods and others in the works will help bring it about:

  1. Taking Exotic States of Consciousness Seriously (e.g. when a world-class phenomenologist says that 3D-printed Poincaré projections of hyperbolic honeycombs make the visual system “glitch” when on DMT the rational response is to listen and ask questions rather than ignore and ridicule).
  2. High-Quality Phenomenology: Precise descriptions of the phenomenal character of experience. Core strategy: useful taxonomies of experience, a language to describe generalized synesthesia (multi-modal coherence), and a rich vocabulary to convey the statistical regularities of textures of qualia (cf. generalizing the concept of “mongrels” in the neuroscience of visual perception to all other modalities).
  3. Phenomenology Club: Critical mass of smart and rational psychonauts.
  4. Psychedelic Turk for Psychophysics: Real-time psychedelic task completion.
  5. Generalized Wada Test: What happens when half of your brain is on LSD and the other half is on ketamine?
  6. Resonance-Based Hedonic Mapping: You are a network of coupled oscillators. Act like it!
  7. Pair Qualia Cartography: Like pair programming but for exploring the state-space of consciousness with non-invasive neurostimulation.
  8. Cognitive Sovereignty: Furthering a culture that has a “Yes &” approach to creativity, keeps track of meta-data, and takes responsibility for the information it puts out.

~Qualia of the Day: Being Taken Seriously~

Relevant links:


Many people report experiencing “higher dimensions” during deep meditation and/or psychedelic experiences. Vaporized DMT in particular reliably produces this effect in a large percentage of users. But is this an illusion? Is there anything meaningful to it? What could possibly be going on?

In this video we provide a steel man (or titanium man?) of the idea that higher dimensions are *real* in a new, meaningful, and non-trivial sense. 

We must emphasize that most people who believe that DMT experiences are “higher dimensional” interpret their experiences within a direct realist framework. Meaning that they think they are “tuning in” to other dimensions, that some secret sense organ capable of perceiving the etheric realm was “activated”, that awareness into divine realms became available to their soul, or something along those lines. In brief, such interpretations operate under the notion that we can perceive the world directly somehow. In this video, we instead work under the premise that we live in a compact world-simulation generated by our nervous system. If DMT gives rise to “higher dimensional experiences”, then such dimensions will be phenomenological in nature.

We thus try to articulate how it can be possible for an *experience* to acquire higher dimensions. An important idea here is that there is a trade-off between degrees of freedom and geometric dimensions. We present a model where degrees of freedom can become interlocked in such a way that they functionally emulate the behavior of a *virtual* higher dimension. As exemplified by the “harmonograph”, one can indeed couple and interlock multiple oscillators in such a way that one generates paths of a point in a space that is higher-dimensional than the space inhabited by any of the oscillators on their own. More so, with a long qualia decay, one can use such technique to “paint” entire images in a *virtual* high dimensional canvas!

High-quality detailed phenomenology of DMT by rational psychonauts strongly suggests that higher virtual dimensions are widely present in the state. Also, the unique valence properties of the state seem to follow what we could call a “generalized music theory” where the “vibe” of the space is the net consonance between all of the metronomes in it. We indeed see a duality between spatial symmetry and temporal synchrony with modality-specific symmetries (equivariance maps) constraining the dynamic behavior.

This, together with the Symmetry Theory of Valence (Johnson), makes the search for “special divine numbers” suddenly meaningful: numerological correspondences can illuminate the underlying makeup of “heaven worlds” and other hedonically-loaded states of mind!

I conclude with a discussion about the nature of “highly-meaningful experiences”. In light of all of these frameworks, meaning can be understood as a valence effect that arises when you have strong consonance between abstract (narrative and symbolic), emotional, and sensory fields all at once. A key turning point in your life combined with the right emotion and the right “sacred space” can thus give rise to “peak meaning”. The key to infinite bliss!

~Qualia of the Day: Numerology~

Relevant links:

Thumbnail Image Source: Petri G., Expert P., Turkheimer F., Carhart-Harris R., Nutt D., Hellyer P. J. and Vaccarino F. 2014 Homological scaffolds of brain functional networks J. R. Soc. Interface.112014087320140873 – https://royalsocietypublishing.org/doi/full/10.1098/rsif.2014.0873


How can a bundle of atoms form a unified mind? This is far from a trivial question, and it demands an answer.

The phenomenal binding problem asks us to consider exactly that. How can spatially and temporally distributed patterns of neural activity contribute to the contents of a unified experience? How can various cognitive modules interlock to produce coherent mental activity that stands as a whole?

To address this problem we first need to break down “the hard problem of consciousness” into manageable subcomponents. In particular, we follow Pearce’s breakdown of the problem where we posit that any scientific theory of consciousness must answer: (1) why consciousness exists at all, (2) what are the set of qualia variety and values, and what is the nature of their interrelationships, (3) the binding problem, i.e. why are we not “mind dust”?, and (4) what are the causal properties of consciousness (how could natural selection recruit experience for information processing purposes, and why is it that we can talk about it). We discuss how trying to “solve consciousness” without addressing each of these subproblems is like trying to go to the Moon without taking into account air drag, or the Moon’s own gravitational field, or the fact that most of outer space is an air vacuum. Illusionism, in particular, seems to claim “the Moon is an optical illusion” (which would be true for rainbows – but not for the Moon, or consciousness).

Zooming in on (3), we suggest that any solution to the binding problem must: (a) avoid strong emergence, (b) side-step the hard problem of consciousness, (c) circumvent epiphenomenalism, and (d) be compatible with the modern scientific word picture, namely the Standard Model of physics (or whichever future version achieves full causal closure).

Given this background, we then explain that “the binding problem” as stated is in fact conceptually insoluble. Rather, we ought to reformulate it as the “boundary problem”: reality starts out unified, and the real question is how it develops objective and frame invariant boundaries. Additionally, we explain that “classic vs. quantum” is a false dichotomy, at least in so far as “classical explanations” are assumed to involve particles and forces. Field behavior is in fact ubiquitous in conscious experience, and it need not be quantum to be computationally relevant! In fact, we argue that nothing in experience makes sense except in light of holistic field behavior.

We then articulate exactly why all of the previously proposed solutions to the binding problem fail to meet the criteria we outlined. Among them, we cover:

  1. Cellular Automata
  2. Complexity
  3. Synchrony
  4. Integrated Information
  5. Causality
  6. Spatial Proximity
  7. Behavioral Coherence
  8. Mach Principle
  9. Resonance

Finally, we present what we believe is an actual plausible solution to the phenomenal binding problem that satisfies all of the necessary key constraints:

10. Topological segmentation

The case for (10) is far from trivial, which is why it warrants a detailed explanation. It results from realizing that topological segmentation allows us to simultaneously obtain holistic field behavior useful for computation and new and natural regions of fields that we could call “emergent separate beings”. This presents a completely new paradigm, which is testable using elements of the cohomology of electromagnetic fields.

We conclude by speculating about the nature of multiple personality disorder and extreme meditation and psychedelic states of consciousness in light of a topological solution to the boundary problem. Finally, we articulate the fact that, unlike many other theories, this explanation space is in principle completely testable.

~Qualia of the Day: Acqua di Gio by Giorgio Armani and Ambroxan~

Relevant links:


Why are we conscious?

The short answer is that bound moments of experience have useful causal and computational properties that can speed up information processing in a nervous system.

But what are these properties, exactly? And how do we know? In this video I unpack this answer in order to explain (or at least provide a proof of concept explanation for) how bound conscious states accomplish non-trivial speedups in computational problems (e.g. such as the problem of visual reification).

In order to tackle this question we first need to (a) enrich our very conception of computation, and (b) also enrich our conception of intelligence.

(a) Computation: We must realize that the Church-Turing Thesis conception of computation only cares about computing in terms of functions. That is, how inputs get mapped to outputs. But a much more general conception of computation also considers how the substrate allows for computational speed-ups via interacting inner states with intrinsic information. More so, if reality is made of “monads” that have non-zero intrinsic information and interact with one another, then our conception of “computation” must also consider monad networks. And in particular, the “output” of a computation may in fact be an inner bound state rather than just a sequence of discrete outputs (!).

(b) Intelligence: currently this is a folk concept poorly formalized by the instruments with which we measure it (primarily in terms of sequential logics-linguistic processing). But, alas, intelligence is a function of one’s entire world-simulation: even the shading of the texture of the table in front of you is contributing to the way you “see the world” and thus reason about it. So, an enriched conception of intelligence must also take into account: (1) binding, (2) the presence of a self, (3) perspective-taking, (4) distinguishing between the trivial and significant, and (5) state-space of consciousness navigation.

Now that we have these enriched conceptions, we are ready to make sense of the computational role of consciousness: in a way, the whole point of “intelligence” is to avoid brute force solutions by instead recruiting an adequate “self-organizing principle” that can run on the universe’s inherent massively parallel nature. Hence, the “clever” way in which our world-simulation is used: as shown by visual illusions, meditative states, psychedelic experiences, and psychophysics, perception is the result of a balance of field forces that is “just right”. Case in point: our nervous system utilizes the holistic behavior of the field of awareness in order to quickly find symmetry elements (cf. Reverse Grassfire Algorithm).

As a concrete example, I articulate the theoretical synthesis QRI has championed that combines Friston’s Free Energy Principle, Atasoy’s Connectome-Specific Harmonic Waves, Carhart-Harris’ Entropic Disintegration, and QRI’s Symmetry Theory of Valence and Neural Annealing to shows that the nervous system is recruiting the self-organizing principle of annealing to solve a wide range of computational problems. Other principles to be discussed at a later time.

To summarize: the reason we are conscious is because being conscious allows you to recruit self-organizing principles that can run on a massively parallel fashion in order to find solutions to problems at [wave propagation] speed. Importantly, this predicts it’s possible to use e.g. a visual field on DMT in order to quickly find the “energy minima” of a physical state that has been properly calibrated to correspond to the dynamics of a worldsheet in that state. This is falsifiable and exciting.

I conclude with a description of the Goldilock’s Zone of Oneness and why to experience it.

~Qualia of the Day: Dior’s Eau Sauvage (EDT)~

Relevant links:

7 Recent Videos: Buddhist Annealing, Is This a Simulation?, The Purple Pill, DMT vs. 5-MeO-DMT, Digital Sentience, Psychedelics and the Free Energy Principle, and Advanced Visions of Paradise

[Context: 3rd in a series of 7-video packages. See the previous two packages: 1st and 2nd]

[Featured image by Wendi Yan.]

Buddhist Annealing: Wireheading Done Right with the Seven Factors of Awakening (link)

This video discusses the connections between meditative flow (any feeling of change) and the two QRI paradigms of “Wireheading Done Right” and “Neural Annealing”. To do so, I explore how each of the “seven factors of awakening” can be interpreted as operations that you do to flow. In a nutshell: the factors are “energy management techniques”, which when used in the right sequences and dosages, tend to result in wholesome neural annealing.

I then go on to discuss two fascinating dualities: (1) The dual relationship between standing wave patterns and vibratory frequencies. And (2) the dual correspondence between annealing at the computational level (REBUS) and annealing in resonance networks.

(1) Describes how the crazy patterns that come out of meditation and psychedelics are not irrelevant. They are, in a way, the dual counterpart to the emotional processing that you are undergoing. Hence why ugly emotions manifest as discordant structures whereas blissful feelings come together with beautiful geometries.

(2) Articulates how simulated annealing methods in probabilistic graphical models such as those that underlie the synthesis of entropic disintegration and the free energy principle (Friston’s and Carhart-Harris’ REBUS model) describe belief updating. Whereas annealing at the implementation level refers to a dissonance-minimization technique in resonance networks. In turn, if these are “two sides of the same coin”, we can expect to find that operations in one domain will translate to operations in the other domain. In particular, I discuss how resisting information (“denial”, “cognitive dissonance”) has a corresponding subjective texture associated with muscle tension, “resistance”, viscosity, and hardness. Equanimity, in turn, allows the propagation of both waves of dissonance, consonance, and noise as well as bundles of information. This has major implications for how to maximize the therapeutic benefit of psychedelics.

Finally, I explain how we could start formalizing Shinzen Young’s observation that you can, not only “read the contents of your subconscious”, but indeed also “heal your subconscious by greeting it with enough concentration, clarity, and equanimity”. Negentropy in the resonance network (patches of highly-ordered “combed” coherent resonance across levels of the hierarchy) can be used to heal patches of dissonance. This is why clean high-valence meditative objects (e.g. metta) can absorb and dissipate the internal dissonance stored in patterns of habitual responses. In turn, this might ultimately allow us to explain why, speaking poetically, it is true that love can heal all wounds. 🙂

~Qualia of the Day: Nirvana Rose~

(Skip to ~10:00 if you don’t need a recap of Wireheading Done Right and Neural Annealing)

[ps. correction – I wrote a 30 page document about my retreat, not a 50 word document]

Relevant Links:


Is This a Simulation? (link)

Will You Take the Simulation Pill?

Warning: Once You Take It There Is No Going Back.

Apologies for the Clickbait. I Can’t Say More Unless You Take the Pill With Me. 🙂

~Qualia of the Day: The Red Pill – With Your Consent, We Will Take It Together~

Relevant Links:


The Purple Pill: What Happens When You Take the Blue and the Red Pill at the Same Time? (link)

The Purple Pill is the pill that gives you both high hedonic tone and an unprejudiced open-ended approach to the pursuit of truth. For losing truth is to lose it all, but to lose it all is only bad because it makes you and others suffer in the wider universe.” – The Purple Pill (Qualia Computing)

In this talk I explain that the “Blue vs. Red Pill” trope relies on a false dichotomy. You don’t need to choose between depressive realism and comforting illusions. Put differently, you don’t need to choose between truth and happiness. High hedonic tone is not incompatible with one’s representational accuracy of causal structures. The world, and the existence of experiential heaven and hell, can be understood without curling into a ball and crying your way to sleep. More so, effective and persistent action towards the good requires that you don’t believe in this false dichotomy, for sustainable altruistic productivity necessitates both accurate models and positive motivations. Thus, the aspiring paradise engineer ought to be willing to take the Purple Pill to move onwards.

I advocate having a balanced portfolio of (1) efforts to minimize experiential hell, (2) techniques to increase the hedonic baseline sustainably, and (3) methods to reliably experience peak states of consciousness in a sane way.

I do not think that spending 100% of one’s time in “destroying hell” is a sustainable approach to life because it does not allow you to “reinvest” in the conditions that gave rise to one’s goodness to begin with (otherwise you become more of a martyr than an effective player in the field!). More so, the relationship between suffering and productivity is non-trivial, which means that to just helping people who suffer extremely does not generally pay off in terms of productive action towards the cause in the future. Hence, improving baseline is just as important: it is precisely what allows people to go from near zero productivity to a high level of productivity. Finally, the benefits of having access to reliable, pro-social ultra-blissful states of consciousness should not be underestimated. They are an important piece of the puzzle because they motivate the “animal self” and are deeply reassuring. Thus, as a “package”, I see a lot of potential in simultaneously reducing negative extremes, improving the baseline, and achieving new heights of bliss. This, to me, is what I see as the path forward.

Topics I cover span: Trungpa’s “Spiritual Materialism” (the attitude of using exalted states of consciousness to “decorate our ego”), optimization problems/reinvesting in the good, sane in-group/out-group dynamics, the game theory of virtue signaling, and the importance of having an explicit commitment to the wellbeing of all sentient beings (to prevent value drift).

~Qualia of the Day: Spiritual Materialism~

Relevant Links:

Thanks Mike Johnson and David Pearce for many conversations on this topic.


DMT vs. 5-MeO-DMT: 12 Key Differences (link)

What are the differences between DMT and 5-MeO-DMT? And what gives rise to those differences? In this video we discuss 12 different ways to analyze the strange and unique effects of these substances. We go over the 9 lenses already discussed in Qualia Computing* and add three more.

Starting with three new lenses (5-MeO-DMT left/DMT right):

A) Global Coherence vs. Competing Clusters of Coherence: 5-MeO-DMT gives rise to a global coherent state (the so-called “unified energy field”), whereas DMT gives rise to an ecosystem of time-loops, each trying to capture as much of your attention as possible, which in turn results in coalition-building and evolution of patterns in the direction of being very “attention grabbing” (cf. reddit.com/r/place).

B) Really Positive or Really Negative Valence vs. Highly-Mixed Valence: 5-MeO-DMT gives rise to either a globally coherent state (high-valence) or two competing coherent states (negative-valence), whereas DMT tends to generate complex consonance/dissonance relationships between the clusters of coherence.

C) How they are different according the the Free Energy Principle: On 5-MeO-DMT the entire experience has to reinforce itself, whereas each cluster of coherence needs to model the rest of the experience in order to be reinforced by it on DMT. Thus 5-MeO-DMT makes experiences that express “the whole as the whole” whereas DMT makes each part of the experience represent the whole yet remains distinct.

And the original 9 lenses:

1) Space vs. Form: 5-MeO is more space-like than DMT.
2) Crystals vs. Quasi-Crystals: 5-MeO generates more perfectly repeating rhythms and hallucinations than DMT.
3) Non-Attachment vs. Attachment: 5-MeO seems to enable detachment from the craving of both existence and non-existence, whereas DMT enhances the craving.
4) Underfitting vs. Overfitting: 5-MeO reduces one’s model complexity whereas DMT radically increases it.
5) Fixed Points and Limit Cycles vs. Chaotic Attractors: 5-MeO’s effect on feedback leads to stable and predictable attractors while DMT’s attractors are inherently chaotic.
6) Modulation of Lateral Inhibition: 5-MeO may reduce lateral inhibition while DMT may enhance it.
7) Diffuse Attention vs. Focused Attention: 5-MeO diffuses attention uniformly over large regions of one’s experiential field, while DMT seems to focus it.
8) Big Chunks and Tiny Chunks vs. A Power Law of Chunks: 5-MeO creates a few huge phases of experience (as in phases of matter) with a few remaining specks, while DMT produces a more organic power law distribution of chunk sizes.
9) Integration vs. Fragmentation: 5-MeO seems to give rise to “neural integration” involving the entrainment of any two arbitrary subnetworks (even when they usually do not talk to each other), while DMT fragments communication between most networks but massively enhances it between some specific kinds of networks.

I also explain what is going on with the “Megaminx DMT worlds” and when DMT entities bully you into believing in their independent existence.

~Qualia of the Day: Rheoscopic Fluid~

Relevant Links:


Digital Sentience: Can Digital Computers Ever “Wake Up”? (link)

I start by acknowledging that most smart and well-informed people today believe that digital computers can be conscious. More so, they believe this for good reasons.

In general, 99.99% of the times when someone says that digital computers cannot be conscious they do so equipped with very bad arguments. This, of course, does not mean that all of these smart people who believe in digital sentience are right. In fact, I argue that they are making a critical yet entirely non-obvious mistake: they are not taking into account a sufficiently detailed set of constraints that any scientific theory of consciousness must satisfy. In this video I go over what those constraints are, and in what way they actually entail that digital sentience is literally impossible.

The talk is divided into three parts: (1) my philosophical journey, which I share in order to establish credibility, (2) classic issues in philosophy of mind, and (3) how we can solve all those issues with QRI’s theory of consciousness.

(Skip to 31:00 if you are not interested in my philosophical journey and you want to jump into the philosophy of mind right away).

(1) I’ve been hyper-philosophical all my life and have dedicated thousands of hours working on this topic: having discussions with people in the field, writings essays, studying qualia in all manners of exotic states of consciousness, and working through the implications of different philosophical background assumptions. I claim that QRI’s views here are indeed much more informed than anyone would assume if they just heard that we think digital computers cannot be conscious. In fact, most of us started out as hard-core computationalists and only switched sides once we fully grokked the limitations of that view! Until the age of 20 I was a huge proponent of digital sentience, and I planned my life around that very issue. So it was a big blow to find out that I was neglecting key pieces of the puzzle that David Pearce, and later Mike Johnson, brought up when I met them in person. In particular, they made me aware of the importance of the “phenomenal binding/boundary problem”; once I finally understood it, everything unraveled from there.

(2) We go over: Marr’s levels of analysis (and “interactions between levels”). The difference between functionalism, computationalism, causal structure, and physicalist theories of consciousness. The Chinese Room. Multiple Realizability. Epiphenomenalism. Why synchrony is not enough for binding. Multiple Drafts Theory of consciousness. And the difference between awareness and attention.

(3) We solve the boundary problem with topological segmentation: this allows us to also provide an explanation for what the causal properties of experience are. The integrated nature of fields can be recruited for computation. Topological boundaries are neither epiphenomenal nor frame-dependent. Thus, evolution stumbling upon holistic field behavior of topological pockets of the fields of physics would solve a lot of puzzles in philosophy of mind. In turn, since digital computers don’t use fields of physics for computation, they will never be unified subjects of experience no matter how you program them.

I also discuss issues with IIT’s solution to the binding problem (despite IIT’s whole aesthetic of irreducible causality, their solution makes binding epiphenomenal! The devil’s in the details: IIT says the Minimum Information Partition has “the highest claim of existence” but this leaves all non-minimal partitions untouched. It’s epiphenomenal and thus not actually useful for computation).

Thanks also to Andrew Zuckerman and other QRI folks for great recent discussions on this topic.

~Qualia of the Day: Dennett’s Intentional Stance~


Relevant Links/References:


Psychedelics and the Free Energy Principle: From REBUS to Indra’s Net (link)

Friston’s Free Energy Principle (FEP) is one of those ideas that seem to offer new perspectives on almost anything you point it at.

It seems to synthesize already very high-level ideas into an incredibly general and flexible conceptual framework. It brings together thermodynamics, probabilistic graphical models, information theory, evolution, and psychology. We could say that trying to apply the FEP to literally everything is not a bad idea: it may not explain it all, but we are bound to learn a lot from seeing when it fails.

So what is the FEP? In the words of Friston: “In short, the long-term (distal) imperative — of maintaining states within physiological bounds — translates into a short-term (proximal) avoidance of surprise. Surprise here relates not just to the current state, which cannot be changed, but also to movement from one state to another, which can change. This motion can be complicated and itinerant (wandering) provided that it revisits a small set of states, called a global random attractor, that are compatible with survival (for example, driving a car within a small margin of error). It is this motion that the free-energy principle optimizes.

Organisms that survive over time must minimize entropy injections from their environment, which means they need to minimize surprise, which unfortunately is computationally intractable, but the information theoretic construct of variational free-energy provides an upper bound on this ground truth surprise, meaning that minimizing it will indirectly minimize surprise. This cashes out in the need to maximize “accuracy – complexity” which prevents both overfitting and underfitting. In the video we go over some of the classical ideas surrounding the FEP: the dark room, active inference, explicit vs. implicit representations, and whether real dynamic systems can be decomposed into Markov blankets. Finally, we cover how the FEP naturally gives rise to predictive coding via hierarchical Bayesian models.

We then talk about Reduced BEliefs Under pSychedelics (REBUS) and explain how Carhart-Harris and Friston interpret psychedelics and the Anarchic Brain in light of the FEP. We then discuss Safron’s countermodel of Strengthened BEliefs Under pSychedelics (SEBUS) and the work coming out of Seth’s lab.

So, that’s how the FEP shows up in the literature today. But what about explaining not only belief changes and perceptual effects, but perhaps also getting into the actual weeds of the ultra bizarre things that happen on psychedelics?

I provide three novel ideas for how the FEP can explain features of exotic experiences:

(1) Dissonance-minimizing resonance networks would naturally balance model complexity due to an inherent “complexity cost” that shows up as dissonance and prediction error minimization when prediction errors give rise to out-of-phase interactions between the layers.

(2) Bayesian Energy Sinks: What you can recognize lowers the (physical) energy of one’s world-sheet. I then blend this with an analysis of symmetrical psychedelic thought-forms as energy-minimizing configurations. On net, we thus experience hybrid “semantic + symmetric” hallucinations.

(3) Indra’s Net: Each “competing cluster of coherence” needs to model its environment in order to synch up with it in a reinforcing way. This leads to attractor states where “everything reflects everything else”.

~Qualia of the Day: Indra’s Net~

Relevant Links:


Advanced Visions of Paradise: From Basic Hedonism to Paradise Engineering (link)

This video was recorded as a way for me to prepare for the speech I gave at the “QRI Summer Party 2021: Advanced Visions of Paradise” (see livestream here). You can think of it as the significantly more in-depth (and higher audio quality!) version of that speech.

The core message of this video is: thinking wholesome, genuinely useful, and novel thoughts about how to build paradise is hard. Doing so without getting caught up in low-dimensional aesthetics and pre-conceptions is very challenging. Most of the “visions of paradise” we find in our culture, media, and art are projections of implicit aesthetics used for human coordination, rather than deeply thought-out and high-dimensional perspectives truly meant to elevate our understanding and inspire us to investigate the Mystery of reality. Aesthetics tend to put the cart before the horse: they tacitly come with a sense of what is good and what is real. Aesthetics are fast, parallel, and collective ways of judging the goodness or badness of images, ideas, and archetypes. They give rise to internal dissonance when you present to them things that don’t fit well with their previous judgements. And due to naïve realism about perception, these judgements are often experienced as “divine revelations”.

To disentangle ourselves from tacit low-dimensional aesthetics, and inspired by the work of Rob Burbea (cf. Soulmaking), I go over what aesthetics consist of: Eros, Psyche, and Logos. Then, to explore high-quality aesthetics relevant to paradise engineering, I go over 7 camps of a hypothetical “Superhappiness Festival”, each representing a different advanced aesthetic: Hedonism, Psychiatry, Wholesome, Paleo, Energy, Self-Organization, and Paradise Engineering. For didactic purposes I also assign a Buddhist Realm (cf. “Opening the Heart of Compassion” by Short & Lowenthal) to each of the camps.

Note: the Buddhist realms are a very general lens, so a more detailed exposition would point out how each of the camps manifests in each of the Buddhist realms. Don’t put too much stock on the precise mapping I present in this video.

~Qualia of the Day: Pure Lands~

Picture by Wendi Yan (wendiyan.com) “The Tower of Paradise Engineering” (also the featured image of this post / image to appear in the forthcoming QRI Book)

For context, here is the party invite/description:

Dear Everyone!

Science fiction and futurism have failed us. Simply put, there is a remarkable lack of exploration when it comes to the role that consciousness (and its exotic states) will play in the unfolding of intelligent agency on Earth. This, of course, is largely understandable: we simply lack adequate conceptual frameworks to make sense of the state-space of consciousness and its myriad properties. Alas, any vision of the future that neglects what we already know about the state-space of consciousness and its potential is, in the final analysis, “missing the point” entirely.

Exotic states of consciousness are consequential for two reasons: (1) they may provide unique computational benefits, and (2) they may have orders of magnitude more bliss, love, and feelings of inherent value.
As Nick Bostrom puts it in Letter From Utopia:

(1) “Mind is a means: for without insight you will get bogged down or lose your way, and your journey will fail.

(2) “Mind is also an end: for it is in the spacetime of awareness that Utopia will exist. May the measure of your mind be vast and expanding.”

In light of the above, let us for once try to be serious consciousness-aware futurists. Then, we must ask, what does paradise look like? What does it feel like? What kinds of exotic synesthetic thought-forms and hyper-dimensional gems populate and imbue the spacetime of awareness that makes up paradise?

Come and join us for an evening of qualia delights and great company: experience and make curious smells, try multi-sensory art installations, and listen to a presentation about what we call “Advanced Visions of Paradise”. Equipped with an enriched experience base and a novel conceptual toolkit, we look forward to have you share your own visions of paradise and discuss ways to bring them into reality.

Infinite Bliss!

Ps. If you are being invited to this event, that means that we value you as a friend of QRI ❤

Pss. Only come if you are fully vaccinated, please!

Key Links:

~Music: People were asking me about the playlist of yesterday’s party. The core idea behind this playlist was to emulate the sequence of aesthetics I talked about in the speech. Namely, the songs are ordered roughly so that each of the 7 camps gets about 1 hour, starting in camp Hedonism and going all the way to camp Paradise Engineering: QRI Summer Party 2021: Advanced Visions of Paradise~


And that’s it for now!

Thank you for tuning in!

Infinite Bliss For All!

A Field Equation to Mend the World

Excerpt from The Science of Enlightenment (2005) by Shinzen Young (p. xv-xvii)

Author’s Preface

It took me quite a while to get to the point of publishing this book — many years actually. That may seem like a strange statement. How can someone not get the point of publishing something they themselves wrote? Let me explain.

A central notion of Buddhism is that there’s not a thing inside us called a self. One way to express that is to say that we are a colony of sub-personalities and each of those sub-personalities is in fact not a noun but a verb–a doing.

One of my doings is Shinzen the researcher. Shinzen the researcher is on a mission to “take the mist out of mysticism.” Contrary to what is often claimed, he believes that mystical experience can be described with the same rigor, precision, and quantified language that one would find in a successful scientific theory. In his opinion, formulating a clear description of mystical experience is a required prenuptial for the Marriage of the Millennium: the union of quantified science and contemplative spirituality. He hopes that eventually this odd couple will exuberantly make love, spawning a generation of offspring that precipitously improves the human condition.

Shinzen the researcher also believes that many meditation masters, current and past, have formulated their teachings with “less than full rigor” by making unwarranted, sweeping philosophical claims about the nature of objective reality based on their subjective experiences—claims that tend to offend scientists and, hence, impede the science-spiritually courtship.

Shinzen the researcher has a natural voice. It’s the style you would find in a graduate text on mathematics: definition, lemma, theorem, example, corollary, postulate, theorem. Here’s a sample of that voice:

It may be possible to model certain global patterns of brain physiology in ways that feel familiar to any trained scientist, i.e., equations in differential operators on scalar, vector, or tensor fields whose dependent variables can be quantified in terms of SI units and whose independent variables are time and space (where space equals ordinary space or some more esoteric differential manifold). It is perhaps even possible to derive those equations from first principles the way Navier-Stokes is derived from Cauchy continuity. In such fields, distinctive “flow regimes” are typically associated with relations on the parameters of the equations, i.e., F(Pj) → Q, where Q is qualitative change in field behavior. By qualitative change in field behavior, I mean things like the appearance of solitons or the disappearance of turbulence, etc. Through inverse methods, it may be possible to establish a correspondence between the presence of a certain parameter relation in the equations modeling a field in a brain and the presence of classical enlightenment in the owner of that brain. This would provide a way to physically quantify and mathematically describe (or perhaps even explain) various dimensions of spiritual enlightenment in a way that any trained scientist would feel comfortable with.

That’s not the voice you’ll be hearing in this book. This book is a record of a different Shinzen, Shinzen the dharma teacher, as he talks to students engaged in meditation practice. Shinzen the dharma teacher has no resistance at all to speaking with less than full rigor. He’s quite comfortable with words like God, Source, Spirit, or phrases like “the nature of nature.” In fact, his natural voice loves spouting the kind of stuff that makes scientists wince. Here’s an example of that voice:

The same cosmic forces that mold galaxies, stars, and atoms also mold each moment of self and world. The inner self and the outer scene are born in the cleft between expansion and contraction. By giving yourself to those forces, you become those forces, and through that, you experience a kind of immortality–you live in the breath and pulse of every animal, in the polarization of electrons and protons, in the interplay of the thermal expansion and self-gravity that molds stars, in the interplay of dark matter that holds galaxies together and dark energy that stretches space apart. Don’t be afraid to let expansion and contraction tear you apart, scattering you in many directions while ripping away the solid ground beneath you. Behind that seeming disorder is an ordering principle so primordial that it can never be disordered: father-God effortlessly expands while mother-God effortlessly contracts. The ultimate act of faith is to give yourself back to those forces, give yourself back to the Source of the world, and through that, become the kind of person who can optimally contribute to the Mending of the world.

Shinzen the hard-nosed researcher and Shinzen the poetic dharma teacher get along just fine. After all, they’re both just waves. Particles may bang together. Waves automatically integrate. Just one problem though. The researcher is a fussy perfectionist. He is very resistant to the notion of publishing anything that lacks full rigor. Spoken words return to silence from where they came from. Printed text sits around for centuries waiting for every tiny imprecision and incompleteness to be exposed.

So it took a while for me to see value in allowing my talks to be published in something close to their original spoken form.


See also:


This video discusses the connections between meditative flow (any feeling of change) and the two QRI paradigms of “Wireheading Done Right” and “Neural Annealing“. To do so, I explore how each of the “seven factors of awakening” can be interpreted as operations that you do to flow. In a nutshell: the factors are “energy management techniques”, which when used in the right sequences and dosages, tend to result in wholesome neural annealing.

I then go on to discuss two fascinating dualities: (1) The dual relationship between standing wave patterns and vibratory frequencies. And (2) the dual correspondence between annealing at the computational level (REBUS) and annealing in resonance networks.

(1) Describes how the crazy patterns that come out of meditation and psychedelics are not irrelevant. They are, in a way, the dual counterpart to the emotional processing that you are undergoing. Hence why ugly emotions manifest as discordant structures whereas blissful feelings come together with beautiful geometries.

(2) Articulates how simulated annealing methods in probabilistic graphical models such as those that underlie the synthesis of entropic disintegration and the free energy principle (Friston’s and Carhart-Harris’ REBUS model) describe belief updating. In contrast, annealing at the implementation level refers to a dissonance-minimization technique in resonance networks. In turn, if these are “two sides of the same coin”, we can expect to find that operations in one domain will translate to operations in the other domain. In particular, I discuss how resisting information (“denial”, “cognitive dissonance”) has a corresponding subjective texture associated with muscle tension, “resistance”, viscosity, and hardness. Equanimity, in turn, allows the propagation of both waves of dissonance, consonance, and noise as well as bundles of information. This has major implications for how to maximize the therapeutic benefit of psychedelics.

Finally, I explain how we could start formalizing Shinzen Young’s observation that you can, not only “read the contents of your subconscious“, but indeed also “heal your subconscious by greeting it with enough concentration, clarity, and equanimity”. Negentropy in the resonance network (patches of highly-ordered “combed” coherent resonance across levels of the hierarchy) can be used to heal patches of dissonance. This is why clean high-valence meditative objects (e.g. metta) can absorb and dissipate the internal dissonance stored in patterns of habitual responses. In turn, this might ultimately allow us to explain why, speaking poetically, it is true that love can heal all wounds. 🙂

~Qualia of the Day: Nirvana Rose~

(Skip to ~10:00 if you don’t need a recap of Wireheading Done Right and Neural Annealing)

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)

Low-Dose Ibogaine + Opioids: A Possible Treatment for Chronic Pain, Schizophrenia, and Depression?

Excerpt from Ibogaine in the 21st Century: Boosters, Tune-ups and Maintenance by Ibogaine treatment experts Patrick K. Kroupa and Hattie Wells


“Dirty” Maintenance

For some, abstinence from narcotic analgesics is not a reality-based goal. Many chronic pain patients are really not going to cast off their crutches [sic], light up some medical marijuana and dance in the meadow, after ibogaine.

In addition to chronic-pain patients, there are many people who are using narcotic analgesics to self-medicate a variety of comorbid conditions. In some cases a “successful” detox from opiates means that somebody can look forward to a lifetime’s worth of maintenance on neuroleptics.

Given the choice between opiates and neuroleptics, there is no simple answer, but the side-effects of current anti-psychotic medications can be devastating. When you compare the quality of someone’s life when they are controlling schizophrenia, for example, through the use of opiates (which tend to have extremely mild side effects) vs. the qualify of life attained using sanctioned medicines (usually neuroleptics, with Cogentin to alleviate some of the side-effects anti-psychotics produce), it is entirely possible, even probable, that the person is happier with the opiates.

Ibogaine is remarkably effective in addressing one of the primary problems in any sort of opiate or opioid maintenance: tolerance. Over time, individuals find they must do extremely high doses of their medications in order to achieve any effect whatsoever.

WARNING: the following category should be considered highly experimental. There is a complete lack of published scientific data regarding the following examples. The difference between 50mg and 500mg is extremely significant and quite possibly fatal. Ibogaine potentiates the analgesic effect of opiates and opioids.

Individual 1: Male, mid-30’s, in good health, who has experienced full-blown resets using ibogaine HCl in the past. His average daily intake was 20Mgs oxycodone and 4–6Mgs hydromorphone (Dilaudid), which he is prescribed for pain management.

By using a very low-dose regimen of 25–50Mgs of ibogaine HCl on a daily basis, he was able to taper down to a point at which 3.75Mg of oxycodone is subjectively providing him with identical pain relief.

He began by taking 25Mg ibogaine HCl per day, and was able to immediately halve his intake of narcotic analgesics with no withdrawal symptoms or discomfort whatsoever. After 6 days he increased the ibogaine HCl to 40Mg, and at week two, he went up to 50Mg a day of ibogaine HCl. After 22 days of ibogaine maintenance, he took a ten day break, before returning to 50Mg which he presently takes every other day. His intake of oxycodone has remained consistent at 3.75Mg/day.

In his own words, “The goal with adding ibogaine to the oxycodone is to minimize if not end the need for it [oxycodone] for pain management. The HCl seems to help with the pain, or at least gives me awareness to take better care of my body by stretching, drinking more water and to get outside for exercise and sunshine.

Most importantly the HCl has given me a feeling of well being and feeling comfortable in my place in the universe, allowing me to process through a depression I have been suffering from. I feel GREAT. The darkness has lifted, the impending doom is cast away! The low dose regimen has also been extremely helpful in musical inspiration; songs I had half-written are coming to completion and new songs are being created. There is a distinct connection between ibo and rhythm/melody, and further underscores for me the important aspect of music in the Bwiti ceremonies.

Individual 2: Female, early 40s, overall good health but suffering from anorexia, has been physically dependent on narcotic analgesics for 19 years. Her use started with heroin and eventually shifted to methadone maintenance and finally hydromorphone (Dilaudid). She has extreme fear and dislike of “tripping” and has repeatedly refused to take a full-blown ibogaine reset.

Her average daily intake was 28Mg of hydromorphone which she “cold-shakes” (breaks down the pills in a cooker so they can be injected) and IVs.

She began by doing 35Mg of ibogaine HCl and was immediately able to stop injecting the hydromorphone and obtained similar analgesia from 24Mg of Dilaudid. Over a period of five days she maintained on 35Mg of ibogaine HCl while continuously decreasing the hydromorphone, which she was taking orally, as prescribed. After five days she was on 16Mg of hydromorphone.

At the start of day 8 she began attending psychotherapy. Over the next two weeks she gradually increased her intake of ibogaine HCl to 50Mg/day, and decreased hydromorphone to 6Mg. On day 19, she took a 10 day break from ibogaine HCl, and her hydromorphone intake rose back to 12Mg/daily (oral), before tapering back down to 6Mg/day within hours of restarting ibogaine maintenance at 35Mg.

At six months out, this cycle appears to be consistent. She takes a break from ibogaine maintenance every 20 days. Slowly drifts from 6Mg/day of hydromorphone, up to 12Mg, before restarting ibogaine at 35Mg/day, at which point she drops back to 6Mg—which appears to be her comfort zone—while gradually increasing ibogaine HCl to 50Mg/day.

She has plans to try a 500Mg dose of ibogaine HCl, and attempt complete cessation of narcotic analgesics.


See also: Low-Dose Ibogaine for Hedonic Tone Augmentation, Anti-Tolerance Drugs, and On Hitting the Actual Target of Hedonic Tone for more up-to-date information.

Coffee Saves Lives

[July 18 2019 addendum: This assumes that coffee has a causal- rather than merely correlational- influence on longevity. See comment section for more details.]


The T-shirt in the featured image was probably designed as a joke, but I take it very seriously.

Indeed, I think there is a strong case to be made that subsidizing coffee could be seen as an Effective Altruist priority. You see, you can save a life with coffee for as little as $50k. This makes coffee an intervention that is on par with some of the top charities in the world, and it is an outlier when it comes to the cost-benefit ratio of medical interventions. Consider how, e.g. this article on QALY states that:

“The UK’s recommendations, for example, are about £20,000 to £30,000 ($30,000 to $45,000) for each additional year of good health, once it has been adjusted to take into account the quality of life. So a drug that achieved 0.5 on the QALY measure would only merit £10,000-15,000 ($15,000 to $22,500).”

Assuming a QALY-adjusted average life-span of about 60 years per person, coffee is about 30 to 50 times more cost-effective than the types of medical interventions the UK is willing to subsidize to extend people’s lives. And that’s not even considering what people themselves are willing to pay to extend their own lives, which is, of course, a lot more than what a government would.

Relative to GiveWell‘s top charities this is still not the best intervention out there (with some of the ultra-effective charities saving a life for about 2,000 dollars). I would nonetheless point out that the ultra-effective charities out there are all effective because they address populations where very basic human needs are not typically met. In Malaria-ridden, war-torn areas, a little can go a long way. But what’s different about coffee is that it is as effective everywhere in the world. Sure, you can save a life with $50k in many African countries. But can you do so in Sweden?! With coffee you can!

Anyhow, how did I arrive at these numbers? Well consider that you can get about 380 doses of coffee for as little as 10 dollars.*

So this means you can have a cup of coffee for as little as 2.63 cents(!). In turn, we know from a lot of research that each cup of coffee up to 4 cups a day prevents about 1/2 micromorts (interestingly, it is just as cost-effective to encourage people who don’t drink coffee to drink 1 cup as it would be to encourage people who drink 3 to go ahead and drink 4).

Given those numbers, we have that the cost of a full life-span worth of micromorts is about $52,631.58.

Why are we not funding this?!


*With: Example 48 oz brand. (we could do even better buying in bulk – I reached out to a delivery company to get a quota and will update when I know more).

Low-Dose Ibogaine for Hedonic Tone Augmentation

Excerpt from Tools of Titans (ps. 119-120) by Tim Ferriss (2017)

Biochemically, Why Is Ibogaine So Oddly Effective?

“[Ibogaine isn’t] just masking the withdrawal like a substitution drug would. For example, if somebody on heroin takes methadone, they won’t have withdrawal for a period of time, but as soon as the methadone leaves the system, the withdrawal comes back. This is not something that happens on ibogaine. You take ibogaine, and the withdrawal is gone – 90% of the withdrawal is completely gone. That’s telling us that the ibogaine is actually changing the receptor to the way it was before the person started using. It’s actually restructuring and healing it. Ibogaine appears to affect almost every major class of neurotransmitter, primarily via NMDA, serotonin, sigma, and nicotinic receptors. A prominent ibogaine researcher, Dr. Kenneth Alper [of New York University School of Medicine], has stated in presentations that certain aspects of ibogaine defy traditional paradigms in pharmacology.”

Tim Ferriss: “I have noticed that microdosing seemed to increase my happiness ‘set point’ by 5 to 10%, to peg a number on my subjective experience. This persists for several days after consumption. Preliminarily, the effect appears to relate to up-regulation of mu-opioid receptors. From one study: ‘…in vivo evidence has been provided for the possible interaction of ibogaine with μ-opioid receptor following its metabolism to noribogaine.’*”

Martin: “[In treating chemical dependency] it’s opiate-specific. We have seen some benefits for certain psychiatric medications, but not for benzodiazepine or alcohol withdrawal. These two withdrawals are actually dangerous. When somebody gets the shakes, it’s DT (delirium tremens) and that can be deadly. So, it’s a very delicate process and somebody who’s physically addicted to alcohol should not take ibogaine. They need to detox first, and then they can take ibogaine for the psychological and the anti-addictive benefits.”


* Bhargava, Hemendra N., Ying-Jun Cao, and Guo-Min Zhao. “Effects of ibogaine and noribogaine on the antinociceptive action of μ-, δ-, and κ-opioid receptor agonists in mice.” Brain research 752, no. 1 (1997): 234-238


See also: Anti-Tolerance Drugs, On Hitting the Actual Target of Hedonic Tone, and A Novel Approach to Detoxification from Methadone Using Low, Repeated, and Cumulative Administering of Ibogaine (from Psychedelic Science 2017).

On Hitting the Actual Target of Hedonic Tone

Practically speaking, I think that our single best psychopharmacological bet for tackling depression, anxiety, and above all chronic pain worldwide in the next decade is to:

1) Identify great, non-toxic, partial mu-opioid agonists with extremely high therapeutic index (e.g. tianepetine, 7-hydroxymitragynine, etc.), and

2) Prescribe them in conjunction with anti-tolerance drugs (such as proglumide, agmatine, black seed oil, small dose ibogaine, etc.).

I think that whomever manages to patent a mixture of partial opioid agonist + anti-tolerance drug that works in the long term will be a multi-billionaire within a couple of years while actually reducing/preventing massive amounts of untold suffering.

imgsrv

Proglumide: A Promising Anti-Tolerance Agent (proof of concept of what is to come)


Ps. My core research at QRI is not pharmacological but rather phenomenological and “patternceutical“. So I am not pursuing the above line of research myself as the core objective of the next few years. But if I was looking into pharmacological options, that’s where I’d shine some light on. If you are in the field, I urge you to look into this option. For more info: “Anti-Tolerance Drugs“.