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.

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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.

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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)

Qualia Computing at: TSC 2020, IPS 2020, unSCruz 2020, and Ephemerisle 2020

[March 12 2020 update: Both TSC and IPS are being postponed due to the coronavirus situation. At the moment we don’t know if the other two events will go ahead. I’ll update this entry when there is a confirmation either way].


These are the 2020 events lined up for me at the moment (though more are likely to pop up):

  • I will be attending The Science of Consciousness 2020 from the 13th to the 17th of April representing the Qualia Research Institute (QRI). I will present about a novel approach for solving the combination problem for panpsychism. The core idea is to use the concept of topological segmentation in order to explain how the universal wavefunction can develop boundaries with causal power (and thus capable of being recruited by natural selection for information-processing purposes) which might also be responsible for the creation of discrete moments of experience. I am including the abstract in this post (see below).
  • I will then fly out to Boston for the Intercollegiate Psychedelics Summit (IPS) from the 18th to the 20th of April (though I will probably stay for a few more days in order to meet people in the area). Here I will be presenting about intelligent strategies for exploring the state-space of consciousness.
  • At the end of April I will be attending the 2020 Santa Cruz Burning Man Regional (“unSCruz“) with a small contingent of members and friends of QRI. We will be showcasing some of our neurotech prototypes and conducting smell tests (article about this coming soon).
  • And from the 20th to the 27th of July I will be at Ephemerisle 2020 alongside other members of QRI. We will be staying on the “Consciousness Boat” and showcasing some interesting demos. In particular, expect to see new colors, have fully-sober stroboscopic hallucinations, and explore the state-space of visual textures.

I am booking some time in advance to meet with Qualia Computing readers, people interested in the works of the Qualia Research Institute, and potential interns and visiting scholars. Please message me if you are attending any of these events and would like to meet up.


Here is the abstract I submitted to TSC 2020:

Title – Topological Segmentation: How Dynamic Stability Can Solve the Combination Problem for Panpsychism

Primary Topic Area – Mental Causation and the Function of Consciousness

Secondary Topic Area – Panpsychism and Cosmopsychism

Abstract – The combination problem complicates panpsychist solutions to the hard problem of consciousness (Chalmers 2013). A satisfactory solution would (1) avoid strong emergence, (2) sidestep the hard problem of consciousness, (3) prevent the complications of epiphenomenalism, and (4) be compatible with the modern scientific world picture. We posit that topological approaches to the combination problem of consciousness could achieve this. We start by assuming a version of panpsychism in which quantum fields are fields of qualia, as is implied by the intrinsic nature argument for panpsychism (Strawson 2008) in conjunction with wavefunction realism (Ney 2013). We take inspiration from quantum chemistry, where the observed dynamic stability of the orbitals of complex molecules requires taking the entire system into account at once. The scientific history of models for chemical bonds starts with simple building blocks (e.g. Lewis structures), and each step involves updating the model to account for holistic behavior (e.g. resonance, molecular orbital theory, and the Hartree-Fock method). Thus the causal properties of a molecule are identified with the fixed points of dynamic stability for the entire atomic system. The formalization of chemical holism physically explains why molecular shapes that create novel orbital structures have weak downward causation effect on the world without needing to invoke strong emergence. For molecules to be “natural units” rather than just conventional units, we can introduce the idea that topological segmentation of the wavefunction is responsible for the creation of new beings. In other words, if dynamical stability entails the topological segmentation of the wavefunction, we get a story where physically-driven behavioral holism is accompanied with the ontological creation of new beings. Applying this insight to solve the combination problem for panpsychism, each moment of experience might be identified with a topologically distinct segment of the universal wavefunction. This topological approach makes phenomenal binding weakly causally emergent along with entailing the generation of new beings. The account satisfies the set of desiderata we started with: (1) no strong emergence is required because behavioral holism is implied by dynamic stability (itself only weakly emergent on the laws of physics), (2) we sidestep the hard problem via panpsychism, (3) phenomenal binding is not epiphenomenal because the topological segments have holistic causal effects (such that evolution would have a reason to select for them), and (4) we build on top of the laws of physics rather than introduce new clauses to account for what happens in the nervous system. This approach to the binding problem does not itself identify the properties responsible for the topological segmentation of the universal wavefunction that creates distinct moments of experience. But it does tell us where to look. In particular, we posit that both quantum coherence and entanglement networks may have the precise desirable properties of dynamical stability accompanied with topological segmentation. Hence experimental paradigms such as probing the CNS at femtosecond timescales to find a structural match between quantum coherence and local binding (Pearce 2014) could empirically validate our solution to the combination problem for panpsychism.

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Qualia Productions Presents: When AI Equals Advanced Incompetence

By Maggie and Anders Amelin

Letter I: Introduction

We are Maggie & Anders. A mostly harmless Swedish old-timer couple only now beginning to discover the advanced incompetence that is the proto-science — or “alchemy” — of consciousness research. A few centuries ago a philosopher of chemistry could have claimed with a straight face to be quite certain that a substance with negative mass had to be invoked to explain the phenomenon of combustion. Another could have been equally convinced that the chemistry of life involves a special force of nature absent from all non-living matter. A physicist of today may recognize that the study of consciousness has even less experimental foundation than alchemy did, yet be confident that at least it cannot feel like something to be a black hole. Since, obviously, black holes are simple objects and consciousness is a phenomenon which only emerges from “complexity” as high as that of a human brain.

Is there some ultimate substrate, basic to reality and which has properties intrinsic to itself? If so, is elementary sentience one of those properties? Or is it “turtles all the way down” in a long regress where all of reality can be modeled as patterns within patterns within patterns ending in Turing-style “bits”? Or parsimoniously never ending?

Will it turn out to be patterns all the way down, or sentience all the way up? Should people who believe themselves to perhaps be in an ancestor simulation take for granted that consciousness exists for biologically-based people in base-level reality? David Chalmers does. So at least that must be one assumption it is safe to make, isn’t it? And the one about no sentience existing in a black hole. And the one about phlogiston. And the four chemical elements.

This really is good material for silly comedy or artistic satire. To view a modest attempt by us in that direction, please feel encouraged to enjoy this youtube video we made with QRI in mind:

When ignorance is near complete, it is vital to think outside the proverbial box if progress is to be made. However, spontaneous creative speculation is more context-constrained than it feels like, and it rarely correlates all that beautifully with anything useful. Any science has to work via the baby steps of testable predictions. The integrated information theory (IIT) does just that, and has produced encouraging early results. IIT could turn out to be a good starting point for eventually mapping and modeling all of experiential phenomenology. For a perspective, IIT 3.0 may be comparable to how Einstein’s modeling of the photoelectric effect stands in relation to a full-blown theory of quantum gravity. There is a fair bit of ground to cover. We have not been able to find any group more likely than the QRI to speed up the process whereby humanity eventually manages to cover that ground. That is, if they get a whole lot of help in the form of outreach, fundraising and technological development. Early pioneers have big hurdles to overcome, but the difference they can make for the future is enormous.anders_and_maggie_thermometer

For those who feel inspired, a nice start is to go through all that is on or linked via the QRI website. Indulge in Principia Qualia. If that leaves you confused on a higher level, you are in good company. With us. We are halfway senile and are not information theorists, neuroscientists or physicists. All we have is a nerdy sense of humor and work experience in areas like marketing and planetary geochemistry. One thing we think we can do is help bridge the gap between “experts” and “lay people”. Instead of “explain it like I am five”, we offer the even greater challenge of explaining it like we are Maggie & Anders. Manage that, and you will definitely be wiser afterwards!

– Maggie & Anders


Letter II: State-Space of Matter and State-Space of Consciousness

A core aspect of science is the mapping out of distributions, spectra, and state-spaces of the building blocks of reality. Naturally occurring states of things can be spontaneously discovered. To gain more information about them, one can experimentally alter such states to produce novel ones, and then analyze them in a systematic way.

The full state-space of matter is multidimensional and vast. Zoom in anywhere in it and there will be a number of characteristic physics phenomena appearing there. Within a model of the state-space you can follow independent directions as you move towards regions and points. As an example, you can hold steady at one particular simple chemical configuration. Diamond, say. The stable region of diamond and its emergent properties like high hardness extends certain distances in other parameter directions such as temperature and pressure. The diamond region has neighboring regions with differently structured carbon, such as graphite. Diamond and graphite make for an interesting case since the property of hardness emerges very differently in the two regions. (In the pure carbon state-space the dimensions denoting amounts of all other elements can be said to be there but set to zero). Material properties like hardness can be modeled as static phenomena. According to IIT however, consciousness cannot. It’s still an emergent property of matter though, so just stay in the matter state-space and add a time dimension to it. Then open chains and closed loops of causation emerge as a sort of fundamental level of what matter “does”. Each elementary step of causation may be regarded to produce or intrinsically be some iota of proto-experience. In feedback loops this self-amplifies into states of feeling like something. Many or perhaps most forms of matter can “do” these basic things at various regions of various combinations of parameter settings. Closed causal loops require more delicate fine-tuning in parameter space, so the state-space of nonconscious causation structure is larger than that of conscious structure. The famous “hard problem” has to do with the fact that both an experientially very weak and a very strong state can emerge from the same matter (shown to be the case so far only within brains). A bit like the huge difference in mechanical hardness of diamond and graphite both emerging from the same pure carbon substrate (a word play on “hard” to make it sticky).

By the logic of IIT it should be possible to model (in arbitrarily coarse or fine detail) the state-space of all conscious experience whose substrate is all possible physical states of pure carbon. Or at room temperature in any material. And so on. If future advanced versions of IIT turn out to be a success then we may guess there’ll be a significant overlap to allow for a certain “substrate invariance” for hardware that can support intelligence with human-recognizable consciousness. Outside of that there will be a gargantuan additional novel space to explore. It ought to contain maxima of (intrinsic) attractiveness, none of which need to reside within what a biological nervous system can host. Biological evolution has only been able to search through certain parts of the state-space of matter. One thing it has not worked with on Earth is pure carbon. Diamond tooth enamel or carbon nanotube tendons would be useful but no animal has them. What about conscious states? Has biology come close to hit upon any of the optima in those? If all of human sentience is like planet Earth, and all of Terrestrial biologically-based sentience is like the whole Solar System, that leaves an entire extrasolar galaxy out there to explore. (Boarding call: Space X Flight 42 bound for Nanedi Settlement, Mars. Sentinauts please go to the Neuralink check-in terminal).

Of course we don’t currently know how IIT is going to stand up, but thankfully it does make testable predictions. There is, therefore, a beginning of something to be hoped for with it. In a hopeful scenario IIT turns out to be like special relativity, and what QRI is reaching for is like quantum gravity. It will be a process of taking baby steps, for sure. But each step is likely to bring benefits in many ways.

Is any of this making you curious? Then you may enjoy reading “Principia Qualia” and other QRI articles.

– Maggie & Anders

Break Out of the Simulation Day: Televised Entity Contact, Injection Pulling Experiments, and the Brain as a Game Engine

[Epistemic Status: Wild Speculations]

TL;DR I came up with a new way to test the reality of DMT entities!

Core idea: Look for signatures of injection pulling in the brain’s connectome-specific harmonic waves. This would distinguish between mere hallucinations (however weird they may feel) and hallucinations being driven by an external source.

Like the study about whether psychedelics can help you see through different Everett branches of the multiverse, I don’t expect the results of this experiment to come out positive. But it’s exciting to see a testable prediction on an otherwise so difficult-to-approach subject matter.


Televised Entity Contact

I think that we can basically assume that a certain percentage of people who vaporize DMT will believe that they contacted mind-independent beings. This is likely the result of hallucinations, but naïve realism and a bias to interpret more intense and detailed qualia as “more real than real external information” is so deeply ingrained that we can take it as a matter of fact that, say, 50%+ of people won’t be able to override their felt-sense of entity presence with heady philosophical epistemic rigor like discussions about the pseudo-time arrow, valence structuralism, or indirect realism about perception.

Is there anything we can do with that? Think of it from an economics arbitrage point of view. If we predict that X number of people will newly believe in DMT entities next year, is there an opportunity there?

I was thinking yesterday on a walk about how “Storm Area 51” is a reality check of sorts for the general public. As in – yes Area 51 is a thing, and no, you can’t just invade it with 100,000 people Naruto running towards it. It was predictable that would be the case, but going through the act in a collective and televised fashion was an interesting exercise in societal epistemology.

 

 

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Along those lines, I suggest that a “Break Out of the Simulation Day” event could be organized. That day we would have, on LIVE TV, people doing DMT trying to contact aliens as a medium, the camera going from one person to the next, always making sure that whoever has the microphone is currently peaking on DMT.

So if the DMT Elves are mind-independent sentient beings and want to send a coherent message to humanity, then that would be the time and place to do it. They would have all of our attention.


Perhaps it is unreasonable to expect DMT Elves to send a coherent message when, surprise surprise, they are on LIVE TV all of a sudden. And this is not only because they won’t have time to dress up. According to people who have tried DMT many times and believe it puts you in contact with other dimensions (cf. Dick Khan’s 600 DMT trip reports) there is an entire ecosystem of entities to contact, each of them with special gifts, powers, intentions, and styles. There are jesters, robots, greys, Archons, angels, demons, wireheading specialists, used alien spaceship dealers (those are the worst), etc. There are entire categories of entities whose sole purpose is to convince you that you are dead, or that you are in a simulation, or that the government is out to get you. There are entire species of entities of the sort that show you how to use sound to create thought-forms, and those that like to discuss with you the impact that the Greeks and Aztecs had on the aesthetics of the reptilians (i.e. interdimensional art historians). You cannot expect to be lucky and get a reasonable DMT entity who (1) will figure out what is going on, and (2) has good intentions for humanity. Perhaps we would be opening ourselves up to influence by incompetent, evil, or incompetent and evil entities. Worse, we would be doing so on LIVE TV!

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by Steven Haman (source)

Testing the Mind-Independent Existence of DMT Entities

Ok, so maybe televising the experiment is a bad idea. Back to the drawing board. Let’s ask: what are the main ways to prove the independent existence of DMT entities? How would serious researchers[1] approach this problem? As far as I can tell, there are three big categories of methods:

  1. Psi-based (having them tell you something about the world you would have no way of knowing otherwise)
  2. Computation-based (having them solve a problem that requires much more computational power than what is available to you with your brain alone)
  3. Quasi-Physical interference-based (have entities literally poke, shake, vibrate, excite, or inhibit your body or nervous system in ways that are impossible on their own)

The Psi-based category is the most well-known, and it includes tests such: (a) asking the entities what your family members are doing right now, (b) having them tell you what is inside a sealed box, (c) having them predict what tomorrow’s lottery numbers will be, and so on. While many people claim to have learned valuable information from DMT entities, I’ve yet to see credible reports of positive tests of this kind.

The computation-based category is perhaps best exemplified by Marko Rodriguez’ suggestion of having the entities factorize a large number for you. This method was popularized by Scott Alexander’s now-famous short story Universal Love, Said the Cactus Person, and then later Gwern made an estimate of the cost of such an experiment. It turns out that testing the hypothesis this way could be as cheap as one thousand (of 2015) dollars. Unfortunately, this test is very hard to conduct (saying 200 digits while on DMT and memorizing sets of numbers with dozens of digits the elves return to you as an answer is not an easy task). So other difficult-to-compute but easy-to-articulate and fast-to-memorize problems might be a better fit in this case. I predict it is only a matter of time before someone seriously tries a variant of this method and reports the results online. I would just caution that, depending on the computational task selected, one may inadvertently discover new computational applications of the DMT state rather than prove the existence of mind-independent DMT entities. After all, unusual states of consciousness may have unique computational trade-offs. See for example: Thinking in Numbers, How to Secretly Communicate with People on LSD, and the discussion about the possible applications for mathematical research of the hyperbolic phenomenal space disclosed during DMT intoxication. Indeed, I would not be surprised to find out that in the year 2100 many of the most important mathematical breakthroughs are taking place in consciousness research centers thanks to having identified states of consciousness capable of rendering exotic mathematical objects and their possible transformations. So before concluding the DMT Elf solved your computationally-demanding problem, it would be important to rule out that it wasn’t you (or the DMT-filled version of you) who solved the problem thanks to novel qualia varieties only disclosed in such a state. That said, this concern only applies to computational tasks that are not extremely difficult. If a DMT alien can factorize a 3000-digit number in 10 seconds then we could actually reasonably conclude that it exists in a mind-independent way.

Now, the 3rd approach is, IMO, both the most likely to work in practice, and also the most spooky and frightening were the results to come out positive. Here is why. I’ve recently received trip reports from rational psychonauts who have taken DMT hundreds of times, and it seems clear that there is a vast number of qualitatively distinct state-spaces disclosed by this substance. One of these such relatively rare idiosyncratic responses caught my attention, and I think it warrants closer scientific scrutiny. Namely, I’ve received reports that when the psychonaut is either tired or has been drinking (why anyone would dare take DMT while drunk is beyond me, but for science-I guess-someone already did it) there is a different kind of experience of a rather unpleasant nature that unfolds. This type of DMT experience is described as getting in contact with the “lower levels of the astral plane” in which parasitic etheric life-forms live (not my words). During such an experience, one may feel that these beings “jitter” your nervous system without asking for your permission to do so. And this is done in such a way that your body may literally get up and dance, as if possessed by a spirit, without your conscious control. In a less extreme presentation of this phenomenon, at the very least the entities seem to jerk one’s extremities whether or not you like it. For example, in one of these trip reports someone described having their arm being pulled and jerked left and right by a demon of sorts while at the same time insectoid life-forms crawled inside their body, into the veins of the tripper. Needless to say, this is a profoundly unpleasant experience, no doubt, but perhaps it is also one of the most empirically testable of the bunch.

Injection Pulling Experiments

The big-picture idea here would be to hook a person up to an EEG during such a state (or even place them in an fMRI if at all possible) in order to determine if the “jittering” experienced is endogenously or exogenously generated.2dof_outofphaseV2.15

How could we do this? Let’s take a step back for a second and recall Selen Atasoy’s study about the influence of LSD on the connectome-specific harmonic waves of the brain. The connectome-specific harmonic waves (CSHWs) are the “natural resonant modes” of a given brain. With this analysis, one can characterize a given “brain state” as a weighted sum of such resonant modes. In turn, one can then see how LSD affects one’s brain state by analyzing the CSHWs while under its influence. As it turns out, there are three major effects from LSD: (a) an overall increase in the power of all CSHWs, (b) the higher-frequency harmonics gain even more power relative to the lower-frequency ones, and (c) the repertoire of possible states dramatically increases, meaning that CSHWs that usually don’t co-occur are more likely to be simultaneously active while on LSD.dynabs-a

The thing to point out is that LSD in this case does not change which harmonic modes the brain has; it merely changes the energy distribution over those harmonics. On the other hand, we could in principle imagine that if the “DMT entity contact” brain state is not purely a hallucination, we would instead find out that such a state has a distinct “non-native harmonic pattern”. And this would manifest in the form of injection pulling and injection locking signatures in the reconstructed patterns of brain activity from the neuroimaging data.N4jchWg

An analogy with a musical instrument is possible: assume that your brain is a musical instrument and that the notes it plays sound like those of a guitar. In this analogy, taking LSD would entail increasing the volume of each note (and especially so for the higher notes) while also increasing the range of possible note-combinations. In other words, while LSD changes what you can play with the guitar, it does not change the fact that you are playing a guitar. That is, the brain states produced by LSD can be explained as different configurations of otherwise native vibratory patterns. In contrast, if DMT entity contact involves an external energy source with its own characteristic resonant modes, then the brain state that results from it would seem to have non-native vibratory patterns. It would be like having a guitar that produces saxophone sounds. You would know that on its own it is not physically capable of producing such sounds, and hence infer it is being externally influenced somehow.

ballspring_2

Are the jiggling patterns of your brain harmonics while on DMT best explained with or without an external metronome and its injection pulling effects?

Such an analysis might reveal that the jerking of the nervous system one experiences on those idiosyncratic DMT experiences is best explained with an injection pulling model and an external metronome marking the pace. In turn, this would imply that the brain is not merely hallucinating a scene, but rather, it is being influenced by an outside metronome. Now, that would be a scientifically-sound ground-breaking finding. And perhaps be so spooky we would all prefer to forget about it rather than contemplate its implications.[2]



Now, there is always the option to interpret all of the unusual phenomenal experiences on DMT with a scientific secular framework that excludes entities from other dimensions. At the Qualia Research Institute, the frameworks that we use to explain such unusual experiences involve what we call algorithmic reductions, namely, identifying a small set of data-structures and information-processing steps that when taken together are capable of generating the vast zoo of complex emergent effects. The advantage of this approach is two-fold. First, we avoid over-fitting by minimizing the information complexity of the model (few data structures and few operations is a vastly more parsimonious explanatory framework than ad-hoc spiritual or atomistic interpretations). And second, it allows us to generate predictions such as the possible existence of exotic phenomenal states that haven’t yet been reported in the literature. Indeed, verifying that its predictions are accurate is one way of validating an algorithmic reduction.

In the case of DMT, we have algorithmic reduction models that explain the unusual properties of space as well as their associated exotic phenomenal time. And while providing compelling explanations for the exotic space and time one can experience in such a state is foundational, we recognize that this is still a first step. I admit that such models still do not go far enough. We still need to explain the nature and unusual character of “entity contact” experiences. So what do we make of them?

The Brain as a Game Engine

Our best guess- for the time being- involves reformulating the nature of the state-space of consciousness to include a layer of “game parameters”. This was first brought up in the essay “Harmonic Society“:

Consider what happens when someone takes LSD. Most people expect that they will simply get to experience new sensations like brighter colors, tracers, or synesthesia. This is true to a point, for light doses. But on medium doses, in addition to exploring the state-space of sensory configurations, one also experiences new aesthetics, which this model would define as ways of organizing a lot of sensations in ways that feel right. More so, an aesthetic is also a way of delivering uninhibited sensations in a way that feels good at the level of the whole experience, from moment to moment. Most people have no clue that there is a vast space of possibilities here.

 

On higher doses, people are surprised to find an even more general way of exploring the state-space of consciousness. Namely, one instantiates alternate games. The DMT “vibe” that people report can be thought of as more than a “context switch”. It is, rather, a more radical change that we could describe as a “game switch”. The “Jester” that people talk about regarding DMT experiences is an archetype that the mind uses to signal the “rule violation” quality of the state. There is so much going on that one’s experience splits into multiple games at once trying to find some common ground, and this feeling of game-incompatibility feels very alien. A sort of anti-virus system in the mind is triggered at that point, and labels the inconsistency with a feeling of weirdness so that you know not to update your actions based on the (currently globally inconsistent) experience of multiple superimposed games. Rule violation through fast changes in implicit games of social status causes you to interpret what is going on as having extreme stakes. Interacting with DMT Aliens, Gods, Elves, etc. feels like the upper limit of potential social status transfer that your world simulation affords (like meeting a president or a king). The state-space of consciousness contains all of these alternate games and metagames, and we have not even begun to catalogue them.

 

Harmonic Society (3/4): Art as State-Space Exploration and Energy Parameter Modulation

In other words, taking DMT does not merely propel you to other regions of the state-space of possible sensory impressions, but it also grants you access to alternate aesthetics[3] and game setups. If you think of your brain not only as a sensory-processing tool, but in fact as a kind of high-level game engine, realizing that God and the Devil can be real in your experience shows that they are possible characters of the games your brain can render. In such a case, we will eventually find that the brain states that render DMT entities are, however exotic, still produced by combining the native resonant modes of one’s own nervous system. No need to invoke neuronal injection pulling from the etheric plane.

Of note is that such a “Game Engine” paradigm would go a long way in explaining unusual experiences such as Free-Wheeling Hallucinations where one becomes able to control almost all features of one’s experience with an incredible level of detail. Indeed we can describe a Free-Wheeling Hallucination state as having access to an experience editor, as illustrated in the Memory Facility Scene of Blade Runner 2049:

Unsurprisingly, we can anticipate that when one is given root access to the parameters of one’s own inner world-simulation, one is likely to focus on creating experiences entirely filled with enjoyable super-stimuli. Whether this involves sex-worlds or proofs of the existence of a benevolent God might be a function of what is it that one craves the most. The intense concern with theodicy and the nature of death while on psychedelic drugs might have something to do with having the ability to change the most essential parameters of one’s internal world simulation. After all, if “living in a world” where God exists and is loving is more enjoyable than the alternative, one’s own hedonic maximization algorithms would try to “realize that’s the truth” if given the option to forge evidence. The same could be going on with DMT entities, for a world in which DMT is an interdimensional portal technology is vastly more interesting (or at least dramatic) than the alternative.

In the end, studying DMT experiences do not need to involve actual entity contact to be of profound significance to the science of consciousness. If you think of your brain as a qualia machine engine, DMT is about the best (or second-best [4]) qualia fuel there is. There are vast regions of the state-space of consciousness that can only be accessed with DMT, many of which contain extremely computationally interesting qualia, and many others which contain intrinsically valuable states (aka. heaven worlds). If, on top of that, it also enables interdimensional beings to injection pull your brain harmonics, we could think of that as icing on the cake.



[1] Serious and Unserious Consciousness Researchers

On a tangential note, here is a quote I recently heard at a consciousness conference:

Thomas Metzinger, the famous and brilliant German neuroscientist and philosopher of mind*, was once asked at a conference presentation he was giving whether he had ever tried psychedelics. His response? “There are two kinds of consciousness researchers. There are the serious ones, and the unserious ones. The serious ones take advantage of all the tools at their disposal to crack this mystery. All I will say is that I am NOT an unserious consciousness researcher.”

*He is best known for being the writer of the books “Being No One” and “The Ego Tunnel“, friends with the Foundational Research Institute, a strong proponent of a variant of eliminativism about consciousness, and a negative utilitarian specializing in AI ethics.



[2] Implications

If the injection pulling experiment does reveal that DMT entities are indeed mind-independent sentient beings in alternate dimensions, then what?

We shall cross that bridge when we get there, but in the meantime, let me entertain you with a wild hypothesis: DMT Elves are us at a higher level of spiritual and psychological development. In such a case, we might want to revise Integral Theory’s levels to include DMT Elves. Expect Ken Wilber’s next book to contain the following:

Larval Stages of the Soul Before Ascension

1) Mythical, 2) Machiavellian, 3) Religious Traditional, 4) Scientific Secular, 5) Postmodern Multiculturalist, 6) Burner, 7) DMT Elf, 8) Full-Spectrum Supersentient Superintelligence, 9) Hedonium Plasma Wave, and finally 10) Pure Love.



[3] An open question for all my DMT-using readers: are DMT visuals more akin to Art Deco, or Art Nouveau?

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[4] On a Serious Note

My prediction is that the single most important tool to investigate consciousness is 5-MeO-DMT. It is probably the most important consciousness tool ever discovered. While I’ve seen serious consciousness researchers and academics admit in private that they have tried psychedelics, I almost never encounter people who have tried 5-MeO. I expect this to change over the course of the next decade as the word gets out that no, 5-MeO is not “yet another psychedelic” but it’s the “real deal” when it comes to disclosing profoundly insightful states of consciousness with implications for personal identity, ethics, the state-space of qualia, the nature of valence (i.e. harmony vs. dissonance), phenomenal time, causality, and the importance of quantum coherence for phenomenal binding. If you have explored this compound and would like to share your insights, please get in touch. We always welcome high-quality trip reports.



 

 

Self-transforming machine thought-forms.
Valued for their intrinsic qualia;
sometimes used for qualia computing.


Featured image source: Machinist Sculpture Chris Bathgate

Early Isolation Tank Psychonautics: 1970s Trip Reports

Excerpt from The Deep Self: Consciousness Exploration in the Isolation Tank by John C. Lilly, 1977 (selected reports between pgs. 186 and 247).

Spring 1974

Richard Feynman, male, 56 years, 160 lbs., 5′ 11”: summary of 35 hours done in 12 weeks, 1974.

Having done a number of introspective experiments on influencing my own dreams (and been objectively conscious and observing while I was dreaming), I became very curious about hallucinations and welcomed the opportunity to use Dr. Lilly’s sensory isolation tanks, for they were reputed to produce hallucinations, safely. I have spent at least a dozen sessions, each of over two hours, in the tank. The experience was very pleasant and rewarding. Although nothing happened for the first two sessions (except idle thinking as when one is going to sleep), hallucinations were experienced nearly every time thereafter. After some brief period after entering the tank, they would continue for hours. I was always aware that I was hallucinating and part of my mind was nearly always making observations. There were the usual out-of-body, or out-of-the-right-time hallucinations. For example, in one case I could see my hands on my head as if I were standing in back, and when I moved my hands (actually in the water) I would see them move and sky appear between the fingers, etcetera. I have later had imaginary flights over scenery, etcetera. In both of these cases the fact that others get this type of hallucination had been discussed beforehand.

On one occasion I had been thinking (in studies of artificial intelligence) about how the masses of memory materials might be organized in storage in the human memory. That week my hallucination consisted of vivid recalling, or reliving, nearly, image after image from far in the past (in no case were there any new details that I didn’t think I could have remembered if asked). But I was delighted to discover that the memories were stored according to locale — you thought of one scene occurring at some particular place and all the other things that occurred at that placed tumbled out. It took a full hour after I was out of the tank until I realized I had discovered nothing real, that that itself was an hallucination.

I am convinced of Dr. Lilly’s dictum that you can think of anything that you want to — that the hallucinations are a delightful and entrancing union of spontaneity of detail with a pattern or set which you have made or can make about their overall character. Thus if you have discussed a great deal about the blue spheres that you will see, you may see blue spheres but have the illusion they come not from you but from somewhere else — even though you know that the only one in the tank is you. The usual test of scientific reality is that many people see the same thing. In this case coincidence of experience lies not in the reality of the thing experienced but from a coincidence of influencing conversations and ideas about what you will imagine, and an illusion that the “image comes to you.” The same phenomena may explain some success in dream interpretations through dreaming certain symbols whose character or interpretation has been previously discussed.

I should like to thank Dr. Lilly, his wife, and associates for many pleasant experiences both in and outside of his tanks.


2 January 1974

Joan Grof, female, 31 yrs., 120 lbs., 5′: 2 hours, 20 minutes.

I entered the tank with the anticipation of several things happening: claustrophobic panic or delineated stages of experience, i.e. sleepfulness, and then visions. Neither set occurred. Instead, I was totally at ease, feeling as though this place (i.e. total quiet, darkness, and fluidity) was what I wanted. I lost body boundaries and time sense, immediately disappeared and I experienced total peace and a feeling of unity. Experience did not modulate and I did not play with it. Just was very passive and let “it” do it itself. What I experienced was a continuous void that was not boring, yet empty, not engaging, yet full.


No date

Stan Grof, male, 42 yrs.: no time recorded.

After about five minutes, enormous slowing down of time. Increasing stability, tranquility, a certain “inorganic quality of consciousness”–moving away from its biological characteristics. Atmosphere of ancient Egypt, becoming aware of her religion, philosophy and art. Insights into the process of mummification, becoming a mummy and experiencing the consciousness typical for it. Understanding it as an interspace vehicle (organic -> inorganic).

Matter -> spirit.

Moving into the initiation in the pyramids, feeling a parallel between a mummy and an adept in the sarcophagus. Awareness of granite, becoming the consciousness of granite. Understanding that the preoccupation with granite in Egypt was based on the appreciation of the state of consciousness associated with it. Changes occur on a scale of thousands of millions of years (as compared to seconds and minutes for biological forms). Return of an old insight: Granite statues are the deities, not the images thereof.

Moving into absolute void (experienced as consciousness of the interstellar space). Timelessness. No difference between minutes and millions of years.

Ending up the experience with feelings of regeneration, purification, refreshment, rejuvenation, clarity.


2 November 1973

Alejandro Jodorowsky, male, 44 yrs.: 1 hour.

It is one experience I would repeat every day, not to obtain, but to lose, like to go to the bathroom. In the first second, I was afraid of being afraid. “It” controls itself saying “It is only afraid to suffocate.” But he (Lilly) must control oxygen, because what will he do with my corpse? This matter of giving [up] my body, and to die to my self-conception. Ok, I will die. After two or three minutes, floating, marvelous comfort, you are at home, nice security, nice silence, nice temperature, and nice relaxation. No body, no sex, no emotions, no thoughts, no problems, no past, but absolutely no past, not plans for future. Little man into the water being the seed fish, without expecting to be a tree with scales. There in the only time, the no-time, there in the only center, the no-center. Sometimes relating with the maternal womb, but escaping of this image. It didn’t want to play with the fetal-paradise and then, it put out like excrement the problem of practical relaxation. Now we are ready. With a great breath of fire the burning of the oxygen like a simple star and a great general beating of heart. Nothing but nothing, and in the middle of the nothingness it was there like a stone–the conscience–Realize what I know, what I live in every moment. I am not so much but still I am something even if I didn’t want it to be active, even if it wanted to be the tongue like a cup without will with all his being made to receive. It tried to be liberated from the little stone when the middle of nothingness became the whole universe. It prepared itself to jump. But Mr. Lilly come, the hour is past. I regret. Was infinite but too short and this body got out of the baptismal desiring a lot of emersions. Anyway, I think, say the little body, I can live in this society in a very polite way in a very communicative way, being immersed all the time in the tank without having a tank.


16 October 1973

Jan Metzner, no data given: no time recorded.

Became aware immediately of tension areas and moved in to relax and give myself to the experience. I was surprised at the nonexistence of fear reactions to closeness/darkness in tank, which I had expected. Being trained as I am in moving in consciousness with the techniques of Light-Fire, I found I went comfortably within and worked with a technique, but found focusing more difficult. My head felt very heavy and had to support it with my hands. Felt salt irritating to the skin. The overall effect was very relaxing, and there are other areas in consciousness I would like to spend time exploring.


16 October 1973

Ralph Metzner, no data given: no time recorded.

I found it a very relaxing and enjoyable experience, marred only by the slight discomfort due to the fact that my head had a tendency to sink down.

I went into the energy-yoga technique I am currently working with and found that I got some unusual perspectives on the innerbody spaces that would be otherwise hard to get to.

Without the restraints of gravity, the moving into and throughout the body and, to an extent, out of it, was much easier–as if the structures had been slightly greased and made more slippery.


2 July 1975

Francisco Varela, male, 28 yrs., 155 lbs.: actual time: 2 hours, 50 minutes.

Closed space, heavy breathing, oppression from suppression. A wave of buoyancy, oily-saltry relaxation, surprise at fitting into water and staying. Letting go, feet are fine, trunk is fine, head is fine.

Beginning to stay–be.

Body goes out, inner sound takes over. Wild ride on heartbeat — inner music. Roller coaster.

Carved into inner sounds: sudden flashes of perception: dogs barking, old tunes on a junky radio, laughter and people’s noise. Startle. Experiment with closed and open eyes. No difference. Stay with eyes open. Visual-acoustic flashes now: scattered, fragmented. Too real. Strong recall of transit stages. I have been here. At a moment: I belong here.

Wilder/surrealist images interface with periods of sleep. In and out with no chance of distinction between dream and tank-reality. Am I there?

Banging. Voice to take me out. Voice is John. Get out. Seems I’ve been in thirty to forty minutes. Long lag in coming back.


No date

Louis Jolyon West, male, 40 yrs., 220 lbs., 6′ 3”: 1 hour.

(N.B.: Previous experience, fresh-water tank, Oklahoma City.)

Buoyancy definitely an advantage over the old method. Also, much better without need for mask.

Lost awareness of surroundings much faster in this situation. Very rapid access to “preconscious stream” (Kubie), with complete immersion therein until termination. No subclassification of mental state during that period would be accurate; my experience was of a smoothly unbroken flow of both digital and analog information. Had planned to meditate (TM) but never got around to it. My personal experience was that a state of “pure consciousness” (more or less) was reached in the tank without utilizing the mental echo of a mantra, but I wouldn’t emphasize this impression without a series of experimental and control sessions. Emerged refreshed with a sense that far less than an hour’s time had passed. A wholly pleasant experience.


10 April 1975

Robert A. Wilson, male, 32 yrs., 170 lbs., 5′ 10”: 2 hours.

Small red light room housing two dumpster-like sensory deprivation tanks. Climbing in the darker, older-looking tank I flash that perhaps it is deeper than the floor level would indicate, but not only ten to fourteen inches of warm water in this giant battery casing. Perhaps there’s not enough water. Sitting, then lying back, the buoyancy is surprising–suddenly I’m floating. Slight contact with tank sides, then my breathing is focus of my attention. Breathing, floating, thinking. Mind floats through myriad of subjects, tension generated within is soon apparent. Return to focus on breath. Thoughts return. After an hour little tastes of terror manifest. Each wave of fear though powerful seeming necessitates reevaluation of tension state, breathing again, floating, adjusting to a deeper relaxation state. Perhaps this is where I’ll sleep tonight. After two hours eyes begin burning, keeping them shut tonight… keeping them shut against the salt becomes a labor, then a drop of salt down my nasal passage–that does it. Sitting up pushing the tank lid open. Fun trip, I feel very relaxed, reborn in a way. Sounds seem much more audible, crickets in the night. Nice to be back.

More Dakka in Medicine

By Sarah Constantin (blog – 1, 2)

The More Dakka story is common in medicine. You do an intervention; the disease doesn’t get better, or gets only marginally better; the research literature concludes it doesn’t work; nobody tries doing MORE of that intervention, but when somebody just raises the dose high enough, it does work.

Examples:

a.) Chemotherapy didn’t work on cancer until doctors made cocktails of drugs, raised the dose so high it would kill you, and then mitigated the side effects with prednisone and intermittent dosing schedules. If they just used a safe daily dose of a single chemotherapeutic agent, they’d have concluded chemo didn’t work.

Prednisone-2D-skeletal

Prednisone

b.) Light therapy barely works for SAD; two internet-famous people have independently found that REALLY BRIGHT light therapy completely fixes SAD.

c.) The example in the post is about allopurinol. Allopurinol prevents gout attacks by lowering uric acid. “In studies, [allopurinol] improved [uric acid] linearly with dosage. Studies observed that sick patients whose [uric acid] reached healthy levels experienced full remission. The treatment was fully safe. No one tried increasing the dose enough to reduce [uric acid] to healthy levels.

d.) The standard treatment for hypothyroidism is thyroid hormone. People with “subclinical hypothyroidism”– people whose thyroid hormone levels are lower than average, but still above the cutoff for hypothyroid, and still suffer from exactly the same symptoms as hypothyroid–, ALSO benefit from thyroid hormone therapy. It’s not standard of care yet, though.

e.) I believe some vitamin deficiencies, don’t remember which exactly, are the same way; there’s an official cutoff for “deficient” but people slightly above that cutoff still have symptoms and still experience symptom relief from supplementation.

f.) Same deal with HIV. Virus has a replication rate & a clearance rate; its replication rate is also its mutation rate; an antiviral drug can raise the clearance rate above the replication rate, which will make the population drop exponentially, but if there’s only one drug the virus will have a chance to evolve to be resistant before the population drops low enough to be undetectable. And this is a simple differential equation that you can calculate years before you know what the drugs even are. One drug: death. Two drugs: death. Three or more drugs: survival.

Luckily David Ho was a physicist and thought about it this way, so when the antiviral drugs came out he was ready to test them in cocktails.

So “single antibiotics don’t work for chronic Lyme but cocktails do and this wasn’t realized for decades” isn’t an unprecedented story. It could turn out that way.

I bet this is something that has a more formal and accurate phrasing, but: if there’s an exponential-growth dynamic (like in a malignant cancer or an infection) where you’re trying to kill the exponentially-growing population, and if there’s a dose-response relationship where higher dose = more killing, then you have a bifurcation point in the outcome as t -> infinity, where a dose below that point means the enemy takes over and the patient dies and a dose above that point means “the enemy is killed faster than it can reproduce and so dies out in the long run.” And in principle you can calculate this cutoff if you know the dose-response relationship, as Ho did.

And separately, there’s a safety threshold; is the minimum effective dose safe or unsafe? With chemotherapy, the minimum effective dose is UNSAFE, which is why they have to get clever with ways to give you doses high enough to kill you while keeping you alive anyway. (Or “find a better drug”, but nobody has found a cytotoxic drug with strictly better tolerability/effectiveness tradeoffs since the 1960’s.)

This is kinda how you get a continuous/analog system to give you discrete outcomes: bifurcation points! Works in gene regulation too. “This regulatory gene turns on that gene’s transcription” – well, what’s actually happening is a continuous scalar, a rate of transcription and a rate of clearance, but because exponential functions are involved you get bifurcations in “steady-state” outcomes over the several-hour timescales needed to get to “this cell has tons of mRNAs for that gene or it’s literally empty of them”.

Systems biology is cool, it explains the math that gets you from a statistical-chemistry model of the cell (as a bag of molecules that bump into each other and have a probability of interaction) to a tinkertoy model that you can treat like a graph. (Gene regulatory networks, protein-protein interaction networks, neuron networks, etc.)

Why Care About Meme Hazards and Thoughts on How to Handle Them

By Justin Shovelain and Andrés Gómez Emilsson

Definition

Nick Bostrom defines an “Information Hazard” as: “A risk that arises from the dissemination or the potential dissemination of (true) information that may cause harm or enable some agent to cause harm.” A more general category is that of “Memetic Hazard”, which is not restricted to the potential harms of true information. False claims and mistaken beliefs can also produce harm, and should thus also be considered in any ethically-motivated policy for information dissemination. 

Introduction

Perhaps one of the best known analysis of meme hazards is the work of Nick Bostrom concerning: Information Hazards, the Unilateralist’s Curse, and Singletons. His focus could roughly be described as one of classifying the types of situations that can give rise to information hazards. A parallel set of problems to that of categorizing memetic hazards is the problem of coming up with policies for dealing with them, and the problem of convincing people that they should care. In this post we suggest some basic heuristics for dealing with meme hazards, and explain why you should care about them even when your work seems unambiguously positive.

Motivation

Why You Should Care

A big problem with getting people to engage with any kind of memetic hazard policy is that it may be perceived as a voluntary constraint on one’s behavior with little to no personal benefit. Nobody (well, at least nobody we know*) gets excited about compliance training at a new job, or inspection day at a manufacturing facility. Subjectively, most people perceive compliance and oversight as something that gets in the way of doing one’s work and as a hassle for one’s organization. That said, there is reason to believe that as the world’s technologies become both more powerful and more widely accessible, that there will be increasingly more dangerous information around. Considering the possible downsides of sharing information will thus become increasingly more important. So at least on a global scale, it will be increasingly more important for people to consider the impact of the information they choose to share. But at an individual level, why would they care about meme hazards policies and not think of them as a bothersome constraint?

Just like there are actions that can help or harm there are ideas that can help or harm. Furthermore, some ideas produce their primary good or bad effect through social transmission, which we can call memes. There are several ways to prevent the harm from memes: not producing them in the first place, not sharing them, or fixing the situation so that when dispersed they do not do damage (before or after dispersal). Let’s call policies to prevent harm from meme hazards, meme hazard policies. Because in a world with increasingly accessible technological power a lot of our largest effects are likely to be produced by memetic hazards, a good way to improve the chances of achieving one’s goals is to tilt things as much as possible towards our goals with good meme hazard policies. It thus makes sense to read works about meme hazard policy and to think about how it bears on one’s work. This way you can improve your implementation and design of meme hazard policies to avoid hampering your own goals. In particular, assuming that you are a rational agent (who both attempts to be epistemically and instrumentally rational) you will generally find that spreading dangerous information that causes large negative effects (even if by accident!) will interfere with your ability to carry out your own goals.

Why Good Work May Have Bad Net Effects

When one engages in very novel research one should be careful to consider the ratio with which one’s work advances desired outcomes relative to undesired outcomes. This may yield surprising results for the net effect of one’s work, sometimes flipping the net effect of research that at first may have seemed unambiguously good. For example, Artificial Intelligence Alignment research may in principle increase the chances of unaligned AI by virtue of providing insights into how to build powerful AIs in general. If it is 100 times harder to build an aligned AI than an unaligned AI, and researching AI alignment advances the goal of building unaligned AIs by more than 1/100 relative to how it advances building aligned AIs, then such research would (counter-intuitively) increase the chances of building unaligned AIs relative to aligned AIs.

As another example of how seemingly good work may have bad net effects let’s consider how information mutates in a social network. As discussed in previous articles such as consciousness vs. replicators there is no universal reason why causing large effects and causing good effects have to be correlated (see also: Basic AI Drives and Spreading happiness more difficult than just spreading). With an evolutionary view, it becomes clear that memes that are good and beneficial to everyone can eventually evolve to become bad and harmful to everyone if by doing so they gain a reproductive edge. As a rule of thumb, you can expect ideas to mutate towards:

    1. Noise due to generation loss
      1. Unless your copying method is perfect or has error correction methods, every time you make a copy of something the information will degrade to some extent. This is called generation loss and it leads to more noisy copies over time.
    2. Simplicity
      1. Since information transmission incurs a cost, simpler mutations of the meme have a reproductive edge.
    3. Ease of memorization and communication
      1. Mutations to the memes that are easier to memorize and communicate are more likely to spread.
    4. Inciting arms races
      1. If the meme provides a competitive edge in a zero-sum game, it may give rise to an arms race between agents who engage in such zero-sum game. For example, a new marketing method discovered by a given agency would force other marketing agencies to invest in researching how to achieve the same results. Since the rate of evolution of a meme is partly determined by the rate at which iterations over it are performed, a lot of memetic evolution takes place in arms races.
    5. Saliency (cognitive, emotional, perceptual, etc.)
      1. Saliency refers to the probability of noticing a given stimuli. Memes that mutate in a way that makes them more noticeable have a reproductive edge. Thus, many memes may over time acquire salient features, such as causing strong emotions.
    6. Uses for social signaling (such as used for signaling intelligence, knowledge, social network, local usefulness, etc.)
      1. Consider the difference between manufacturing a car that focuses exclusively on basic functionality and a car that in addition also signals wealth. Perhaps it would be better if everyone bought the first kind of car because the second kind incites the urge in others to get a new car more often than necessary. Namely, people might want to buy a new car whenever the neighbors have upgraded to a more luxurious car (see: Avoid Runaway Signaling in Effective Altruism and Keeping up with the Joneses).
    7. Overselling
      1. As a general heuristic, memes will spread faster when they are presented as better than they really are. Unless there is a feedback mechanism that allows people to know the true value of a meme, those that can oversell themselves will tend to be more common relative to those that are honest about the value they provide.
    8. Usefulness
      1. The usefulness of a meme increases the chances that it will be passed on.

Given considerations like the above, it’s clear that in order to achieve what we want we need to  think carefully about the possible impacts of our research and efforts, even when they seem unambiguously positive. Now, when should one give special thought to memetic hazard policies?

When Should You Care the Most?

meme_hazard_action_space

Meme Hazard Action Space – Worry when the ideas are both novel and have the potential to have large effects

There are two key features of potential memetic hazards that should be taken into account when thinking about whether to pursue the research that is bringing them to life. 

The first one is how large their effects may be, and the second is how novel they are. How large an effect is depends on factors such as how many people it may affect, how intense the effects would be on each person affected, how long the effects would last, and so on. How novel a meme is depends on factors like how many people know about it, how much specialized knowledge you require to arrive at it, how counter-intuitive it is, and so on.

No matter how novel a piece of information may be, if it does not have the potential to cause large effects we can disregard it in the context of a meme hazard policy. When the potential to cause large effects is there but the idea is not very novel, then one should focus on actions to mitigate risks. For instance, if everyone knows how to build nuclear bombs, then the real bottleneck to focus as a matter of policy would be on things like the accessibility to rare or expensive materials needed to build such bombs.

But when the information is both novel and can cause large effects, then the appropriate focus is that of a meme hazard policy based on strategies to handle information dissemination.

Examples

Ignore:

  • What you had for breakfast, yet another number sorting algorithm, how to get the hair of a cat to be more fluffy

Focus on ideas:

  • A more efficient deep learning technique, a chemical to improve exercise response efficiency, a new rationality technique, information on where the world’s biggest tree is

Focus on actions:

  • The idea of guns, the idea of washing hands for sanitary purposes, running an Ayahuasca retreat in the amazon

Suggested Heuristics

yes_no_diagram_3

Suggested Responses

To wrap up, here we provide a very high-level set of suggested heuristics to consider if one is indeed discovering ideas that are both very novel and capable of producing large effects:

  • Develop
    • Develop if you conclude that there is no risk
  • Share
    • Share if you conclude that there is no risk
  • Log your analysis and proceed
    • Store the results of your analysis for future use by others who may overlook the risks and then continue developing or sharing it
  • Think more about it
    • Conclude that it would be valuable to analyze the risks of the meme (e.g. a new technology) further
  • Develop cure
    • Develop a cure of the meme hazard’s downsides
    • This approach may entail selectively sharing the information with people who are highly benevolent, good at keeping secrets, and capable in the relevant domains of expertise
  • Improve the groups that receive it so that it is safe
    • Some information is only risky if certain types of groups get it, so if you change the nature of the groups then there is no risk
  • Framing it so it goes to the right people or only yields good effects
    • The way an idea is posed or framed determines a fair amount of who will read it and how they will act on it
  • Selecting a safe subset to share
    • When you have information it could be that some parts are good or safe to share and you can selectively share those parts
    • Make sure those parts are not sufficient to reconstruct the original (unsafe) information
  • Selecting a safe subset to develop
    • When developing some information it can be that some parts are good or safe to develop and you can selectively develop those parts
  • Selectively share to a subset of people
    • Some information is only risky if certain types of groups get it; if you can aim where the information goes you can avoid the risk
    • Report the information to proper authorities
  • Don’t develop
    • Some information is too risky to develop
  • Don’t share
    • Some information is too risky to share
  • Monitor to see if others move towards developing or sharing it
    • If you’ve identified something risky it may make sense to see if others are developing it or likely to share it so that you can warn them, focus on building a cure, contact authorities, or start changing your actions knowing that a disaster is likely. 
  • Try to decrease the likelihood of rediscovery
    • If it’s really risky you may want to see what you can do about decreasing the likelihood that it is rediscovered

Conclusion

In this post we discussed why you should consider following heuristics to deal with meme hazards as an important part of achieving your goals rather than as a chore or hassle. We also discussed how work that may seem unambiguously good may turn out to have negative effects. In particular, we mentioned the “ratio argument” and also brought up some evolutionary considerations (where memes may mutate in unhelpful ways to have a reproductive edge). We then considered when one should be especially cautious about meme hazards: when the information is both highly novel and capable of producing large effects. And finally, we provided a list of heuristics to consider when faced with novel information capable of producing large effects.

In the future we hope to weave these heuristics into a more complete meme hazard policy for researchers and decision makers working at the cutting edge.


*After posting this article someone contacted us to point out that they in fact love compliance training. This person was very persistent about updating this post with that fact.

Carhart-Harris & Friston 2019 – REBUS and the Anarchic Brain

Reposted from Enthea with permission from the writer: 


Drs. Robin Carhart-Harris and Karl Friston recently published a beautiful paper – REBUS and the Anarchic Brain (a).

It’s great for two reasons:

  1. It presents a plausible unified theory of how psychedelics work.
  2. It’s a wonderful jumping-off point into the literature. Every paragraph is full of pointers to research that’s come out in the last 5 years, and boy are there a lot of rabbit holes to go down – it’s filled out my reading list for the next several months.

Carhart-Harris is the director of Imperial College London’s newly minted Centre for Psychedelic Research; Friston is a famous neuroscientist.

REBUS is a (somewhat dubious) acronym for RElaxed Beliefs Under pSychedelics. The basic idea: psychedelics reduce the weight of held beliefs and increase the weight of incoming sensory input, allowing the beliefs to be more readily changed by the new sensory information.

REBUS pulls together Carhart-Harris’ Entropic Brain theory and Friston’s Free Energy Principle, both of which relate to the hierarchical predictive coding model of cognition. There’s a lot of jargon & nuance here, but the essential idea of hierarchical predictive coding is pretty straightforward:

  • The brain generates mental models that predict upcoming sensory inputs. (The predictions are called “priors,” as in “prior beliefs.”)
  • These predictive models are layered on top of each other in a hierarchy – the higher levels send predictions down the hierarchy; the lower levels report sense data upwards.
  • In cases where the model’s top-down predictions do not match the bottom-up sensory input, the model either (a) updates its priors based on the new sense data, or (b) ignores the sense data and maintains its priors.

(Scott Alexander’s review of Surfing Uncertainty has a lot more on predictive coding.)

Carhart-Harris & Friston theorize that the main thing psychedelics are doing is relaxing the weight of the brain’s top-down prediction-making (“REBUS”) and increasing the weight of the bottom-up sense information (“the Anarchic Brain”). This allows bottom-up information to have more influence on our conscious experience, and also on the configuration of the hierarchy overall.

Carhart-Harris & Friston analogize this process to annealing – heating up a metal dissolves its crystalline structure, then a new structure recrystallizes as the metal cools:

The hypothesized flattening of the brain’s (variational free) energy landscape under psychedelics can be seen as analogous to the phenomenon of simulated annealing in computer science – which itself is analogous to annealing in metallurgy, whereby a system is heated (i.e., instantiated by increased neural excitability), such that it attains a state of heightened plasticity, in which the discovery of new energy minima (relatively stable places/trajectories for the system to visit/reside in for a period of time) is accelerated (Wang and Smith, 1998).

Subsequently, as the drug is metabolized and the system cools, its dynamics begin to stabilize – and attractor basins begin to steepen again (Carhart-Harris et al., 2017). This process may result in the emergence of a new energy landscape with revised properties.

Psychedelics “heat up” the brain, increasing plasticity and weakening the influence of prior beliefs. As the psychedelic stops being active, the brain “cools” – the hierarchy re-forms, though perhaps in a different configuration than the pre-psychedelic configuration.

This explains how psychedelic trips can cause changes that last long after the substance has exited the body – in those cases, the psychedelic facilitated a change in the organization of the brain’s cognitive hierarchy.

Psychedelic therapy is showing promise for mental disorders associated with too-rigid thought patterns – depression, anxiety, addictions, maybe OCD, maybe eating disorders. In predictive-coding lingo, “disorders that may rest on particularly rigid high-level priors that dominate cognition.”

In these disorders, new information can’t revise the existing story of how things are, because strong priors suppress the new info before it can update anything.

The REBUS model straightforwardly explains how psychedelics help with disorder like this – by relaxing the strong top-down priors and boosting the bottom-up inputs, bottom-up inputs have more ability to effect the system. Here’s an illustration from the paper:

rebus-schema

The top sketch is a brain where strong top-down priors dominate. New sensory inputs are suppressed and can’t update the hierarchy. The bottom sketch is the same brain while on a psychedelic – the top-down priors have been relaxed and bottom-up sensory information flows more freely through the system, causing a bigger impact.

Okay, nice theory, but can we observe this in the brain? Is there any evidence for it?

Carhart-Harris & Friston place the default mode network at top of the brain’s predictive hierarchy. The default mode network is the network of brain regions that’s most active when the brain isn’t engaged with any specific task. It also appears to be the seat of one’s sense of self. The default mode network is intensely relaxed by strong psychedelic experiences – this is subjectively felt as ego dissolution, and allows for the propagation of bottom-up sense data (which are also boosted by psychedelics).

Carhart-Harris & Friston identify two mechanisms by which psychedelics may relax the default mode network – activation of 5-HT2AR serotonin receptors (there are lots of these receptors in the default mode network), and disruption of α and βwave patterns, which seem to propagate top-down expectations through the brain (and are correlated with default mode network activity).

In addition to the brain-scan-style evidence they cite throughout the paper, Carhart-Harris & Friston dedicate a long section to behavioral evidence (“Behavioral Evidence of Relaxed Priors under Psychedelics”). Briefly, there are several studies showing that surprise & consistency-making responses to sensory stimuli are reduced while on psychedelics, which is what we’d expect if the influence of top-down priors was lessened.

To sum up, REBUS and the Anarchic Brain places psychedelics in a predictive coding framework to give a unified theory of what psychedelics do – they decrease the influence of top-down prediction-making and increase the influence of bottom-up sense data. The theory has the nice quality of tying many disparate psychedelic phenomena together with an underlying explanation of what’s going on. Plus, it gives a brain-based explanation for why psychedelic therapy is helpful for disorders like depression, anxiety, and addiction.



See also: Mike Johnson’s pieces A Future for Neuroscience and The Neuroscience of Meditation which summarize a lot of the research by the Qualia Research Institute (QRI) on this topic. In particular, much like this paper by Carhart-Harris and Friston, at QRI we’ve been working on integrating the neuroscientific paradigms of Entropic Brain, Connectome-Specific Harmonic Waves, Predictive Coding, and our own contribution of Neural Annealing into a unified theory of psychedelic action for a number of years.

Our first mention of Neural Annealing in relation to psychedelics was in Algorithmic Reduction of Psychedelic States in 2016, and we are pleased to see that the concept is becoming a live idea in academic neuroscience in 2019.*

From our point of view, an extremely promising area of research that mainstream neuroscience has yet to explore is the Symmetry Theory of Valence. In particular, we claim that the very reason why Neural Annealing improves not only global control, belief, and behavioral consistency, but also mood and sense of wellbeing is because it smooths and symmetrifies your neural patterns of activation. Will this turn out to become part of mainstream neuroscience in the future? Well, since QRI was calling Neural Annealing years in advance, perhaps in retrospect you’ll also see that we were on the money when it came to the mathematics of valence. Only time (and funding) will tell.


*It should be noted that unbeknownst to us Steven Lehar might be the first person to discuss neural annealing in the context of psychedelic states of consciousness. In his 2010 book “The Grand Illusion” he talks about annealing on LSD and ketamine. Here are some key articles about it: Free-Wheeling Hallucinations, The Resonance and Vibration of [Phenomenal] Objects, The Phenomenal Character of LSD + MDMA, and From Point-of-View Fragmentation to Global Visual Coherence: Harmony, Symmetry, and Resonance on LSD.


Featured image credit: Michael Aaron Coleman

Ephemerisle: Health Homeostasis, Worldview Annealing, and the Long-Tails of Serious Fun

Idealism leads to realism if it is strictly thought out.

Ludwig Wittgenstein (from Notebooks, 1914-1916)

I just came back from spending a week on the water at Mandeville Point (~18 kilometers from Stockton, California), at a yearly gathering called Ephemerisle. Below I will share some thoughts, insights, and takeaways from this experience.


Introduction

Ephemerisle is an event first conceived as a social experiment to investigate how the construction of autonomous floating nation-states could work in practice. The history of Ephemerisle is full of interesting lessons in how ideologies react when subjected to the acid bath of reality (cf. mini-documentary about the first iteration of the event). Over the years, this event has evolved from a wild, loosely organized libertarian congregation of like-minded individuals with no central planning, no rules, and no taxes, into a -somewhat- tamer, loosely organized libertarian congregation with central planning, rules, taxes, insurance, and heavy legal waivers that you need to sign when boarding islands and vessels. Despite the introduction of rules and legal waivers, the overall vibe of the place is one of freedom, intellectual intensity, and a spirit of giving.

To gain a sense of the scale of the event I’d recommend looking at drone footage over the years: 2015, 2016, 20172018, and 2019. Compared to Burning Man, this is a relatively tiny event, with a crowd that reaches up to perhaps as many as 600 people throughout the week, the equivalent of only 1% of the population of Black Rock City. In absolute terms, however, it is certainly very impressive to see that many people organized into a superorganism capable of delivering the basic survival needs for hundreds of persons in such an inhospitable environment, along with the luxuries of dance floors, sound systems, massage bunks, and trippy art.

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Ephemerisle 2019 – Credit: Sameer Halai

The captain of the ship in which I camped said that “the slogan of Ephemerisle should be ‘Figure It Out'”. Indeed, this event falls in the same category as Burning Man when it comes to the degree of self-reliance that it demands from each participant. Burning Man, as noted before, could very well be called “the annual meeting of the recreational logistics community”. Ephemerisle takes all of the hassle and preparation needed for Burning Man, doubles it, adds an extra dose of uncertainty, and sprinkles it with a number of challenges unique to living on the water for a week.

map_of_ephemerisle.png

Location of Ephemerisle 2019

Indeed, attending Ephemerisle is not a simple task. The starting section of the Ephemerisle survival guide reads:

The first thing to realize about Ephemerisle is that it is not a festival. There are no tickets, no gates, and no central authority whatsoever. But Ephemerisle is on the water, which makes attending a very non-trivial task.

 

You are responsible for getting yourself to and from the event site and for everything you’ll need to live there and survive for your stay. There are few to no resources adjacent to the event site, and none on the water. Think carefully about what you’ll need, and plan ahead!

So, given the time, effort, resources, knowhow, and social connections needed to be able to attend, who actually ends up going to Ephemerisle?

Participants

Like Burning Man, the people at Ephemerisle are not representative of the general population.

Stating the obvious, the mean conscientiousness, openness to experience, and general intelligence of participants are all significantly above the mean relative to the general population. I might add that, based on many conversations I had, it seemed that the following qualities are also significantly more common relative to the general population: graduate studies, social skills, physical fitness, cryptocurrency investments, and of course, number of yachts owned.

What stuck with me was not only the average intelligence of the participants, but also the high density of particularly brilliant people doing impressive work of their own in fields such as nanotechnology, computational biology, machine learning, cryonics, innovation in politics, and many other heavy-duty intellectual fields. I lost count of the number of serial entrepreneurs, people with PhDs in STEM fields from MIT, and advanced meditators working on developing transformative technologies.

I asked people who have been to many Ephemerisles how to explain this unusual density of spiky people, and the answer seems to be a mixture of self-selection and founder effects. First, it takes some degree of agency and determination to choose to attend this event and do all the things you need to do to make it happen. And second, a large number of people attend via invitation from well-established boats and islands, which in turn were seeded by very impressive persons from the late 2000s/early 2010s Bay Area super-cluster of people working on seasteading, longevity, AI safety, and transhumanism. Taken together, these two factors make Ephemerisle a natural Schelling point for energetic people doing cool things to find one another.

If I were to cluster the population of Ephemerisle this year, I’d intuitively estimate that 35% of people are in the broad people-cluster of scientists, libertarians, anarchists programmers, entrepreneurs, cryptocurrency developers, Bay Area rationalists, and psychedelic users. 30% are people in the broad cluster of artists, off-the-grid environmentalists, Oregon ecosystem-oriented hippies, and psychedelic users. 20% are people who live physically nearby, who own a boat, and for whom it is relatively convenient to attend. 10% are people with a festival-oriented lifestyle (to the point that their main activity is to go from festival to festival), and the remaining 5% are real-life hard-core sailors who help trouble-shoot the most difficult problems that (inevitably) arise during the event.

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Ephemerisle 2015

But Why?

Why are people willing to spend so much time and energy into making an event like this happen? Why not stay at home or go to a club, where the chances of drowning, breaking bones, and getting sepsis from exposing open wounds to delta water are orders of magnitude lower? Why bother to learn knotsanchoring, and how to handle a fire on your boat when you could instead learn to use a remote control, watch TV, and order a pizza? Why the need to carry bucketloads of water to and from different boats for hours at a time when you could simply drink tap water from the comfort of a vacation timeshare apartment? And if you are attending to meet smart people working on cool projects, why not go to a conference or visit an academic department?

I would claim that the thirst for adventure, fear of missing out, and ideological excitement can only go so far in explaining over-the-top events like Ephemerisle. To bridge the explanatory gap here we will need something more. This is why I will offer two analytic angles for explaining high-effort events like Ephemerisle: (1) Health Homeostasis (condition-dependence-based fitness signaling), and (2) Worldview Annealing (as a cure to adultification and the regeneration of a positive internal mental representation of one’s conception of humanity). Let me explain:

Health Homeostasis

This analytic angle comes from evolutionary psychology. In particular, genetic fitness signaling dynamics may explain why some people may have the urge to do wild and risky things when they are exceptionally smart and healthy. The concept of “condition-dependance” comes handy here:

Condition-dependence: A trait’s sensitivity to an animal’s health and energy level. For example, dance ability is condition-dependent because tired, sick animals can’t dance very well. (Mating Mind by Geoffrey Miller, from Glossary, pg. 437)

From a gene’s eye view, it makes no sense for genetically robust individuals to spend one’s healthy years in relative security, for one would have no way to advertise one’s good genes relative to average specimens in such conditions. In a sense, doing complex and risky activities is a hard-to-fake signal of fitness. Therefore, from the point of view of one’s genes, self-interest might (metaphorically) reason: “I have all this health and energy laying around, better don’t let it go to waste and use it to signal genetic fitness instead” (see: An Infinite Variety of Waste).

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Ephemerisle 2009. Credit: Christopher Rasch

This could be summarized with a general principle I call Health Homeostasis, which posits that among sexually-reproducing species who engage in fitness displays, we can expect that individuals will have a “desired level of health”. If they notice that they are below that level of health, they will increase the time and resources focused on regenerating health. And if they notice that they are above that level of health, they will instead reduce the time and resources focused on regenerating health, and engage in costly genetic fitness signaling displays. Perhaps events like Burning Man and Ephemerisle have an element of this going on. They are appealing to people who have too much health and for whom the standard ways of signaling fitness simply won’t cut it. They need health-diminishing activities in bulk. They need challenges where they can display physical endurance while exercising their powers of creativity. And this is why, all considered, these events are so sexy.

I should add here that I am not suggesting that this explanation implies that participants are doing this consciously. Executing an adaption rarely involves conscious planning and strategizing. All it requires is following the gradient of what feels right and good.

Introspect, dear reader, about the times where you have felt the most alive. Have you, perhaps, not experienced them during risky situations? When you felt that “this could be a real danger to other people”? When by luck or grace you happened to be willing and able to do something few others could have done? This is what I am talking about. This feeling of reality and authenticity may very well be a good proxy for the process of down-regulating your health. And this is what it looks like for health homeostasis to be at play.

Worldview Annealing

This event was- to be open and real with you- quite moving to me. I struggle to give words to some of the feelings, intuitions, and thoughts that I experienced towards the end of my stay. The situations in which I found myself made me feel new sensations about the possibilities hidden in humanity and the unfolding of intelligence on this planet. It felt mystical and significant. It’s as if we were glimpsing the birth of a new stage for humanity.

Something akin to this happened to me at Burning Man a few years ago (with a slightly different flavor). How do I explain it? Someone I met there shared the view that at Ephemerisle we are experiencing a certain kind of “chemistry of consciousness” that is unique to the space. That collectively, in a space of this sort, we all resonate with a set of ideals, conscious efforts, and love that makes the whole environment vibrate with a unique quality of consciousness tuning the participants to a new level.

Perhaps! We could very well throw the towel and declare victory to mysterianism at this point! Alas, this is not the path that Qualia Computing has ever taken before.

So how can we explain the deep emotional feelings induced by Ephemerisle and events akin?

Here is the big picture idea: There are elements about the experience there that give rise to “heightened states of consciousness” for many hours at a time. This can be explained largely due to the build-up of semantically-neutral energy thanks to the high-density of surprising stimuli (cf. free-energy principle, entropic disintegration, and neural annealing). Over the course of several days, such build-up of semantically neutral energy enables neural search processes that solve constraint satisfaction problems that have to incorporate the fact that hundreds of human volunteers can come together to peacefully construct a mini-world in a treacherous environment, all for the benefit and enjoyment of others. Integrating this experienced fact can lead to the felt-sense that the world could be better, much better. That we could create heaven-worlds for each other. That the future could be a place of loving-kindness energized with electrifying creativity and positive energy. By the end of the event, one’s cynical internal representations of humanity have been replaced -to an extent anyhow- by optimistic and loving thought-forms. It is hard to see the creation of such a beautiful thing without shifting one’s priors about the real world.

It is important to realize that changing one’s deep representations of high-level concepts such as humanity and the world can have far-reaching ramifications. The emotional valence that is attached to our big-picture ideals can determine how we see the world. A somewhat far-fetched but ultimately accurate analogy could be made with Rubik’s cubes: Imagine that a “perfect state of the world” is equivalent to a “completely solved Rubik’s cube”. In addition to the degree to which you are close to a fully-solved state, you also have preferences about the aesthetics of the colors of the cube. But ultimately, you care more about the cube being solved than you care about the cube having pretty stickers.

Now, let’s say that we start with a completely scrambled state, which you feel very bad about. If you feel hopeless about being able to unscramble it, you can focus on improving the look of the stickers. The stickers could be more pretty and that will briefly make you feel good, but you will know that doing any surface modification still does not help in rearranging the entire cube so that it is in a solved state. The analogy here is: changing the look of the stickers is akin to many of the band-aid solutions we use in our life. We try to make ourselves feel better by doing superficial things like changing our cars, our appearance, and our job titles. But deep down, none of that addresses the deeper sources of dissatisfaction. The cube of our life remains in an unsolved- if more outwardly pretty- state.

There could also be uncertainty about how far you are from the perfectly solved state. Especially when you are unfamiliar with the algorithms that work for solving the cube, you will find that there are configurations that give the impression of high disorder that are in fact close to getting the cube solved. And then there are situations that seem close to the goal line of a completely solved cube that still require a lot more work to figure all out. The same could be with the state of our lives.

Now, what do I mean with a perfectly solved cube? I’m referring to a sense that “everything is as it should be”. I would argue that for many people, the very idea that humanity cannot get its shit together is a deep source of discomfort. Changing jobs, romantic partners, living situations, and perhaps even political parties do little to address this deep problem. They could be thought of as akin to trying to make the Rubik’s cube more pretty by decorating the stickers.

Experiences where one gets a sense that humanity, if properly focused, could indeed get its shit together might have a much deeper emotional effect on people than one might intuitively realize. All you may need is a proof of concept to create a glimmer of hope. All you need is someone showing you a video of speedcubing for you to realize that there is a short path from the state of your cube to a fully-solved state. And this can be exhilarating and deeply moving.

Now, for this to take place, we need to be on a flexible state of mind. Hence the importance of art, meditation, philosophy, and psychedelics in conjunction with the unfamiliar space. This is the recipe for annealing a big picture change of mind -a reframing of humanity, its possibilities, and one’s place in it. It indeed requires multiple days of iterations of changes of one’s mental representations. Here, meditation, art, psychedelics, and philosophy synergize with the scene in order to raise the brain’s energy parameter. The scene adds a lot of novelty: confrontation with the necessities for survival, extended exposure to people who are smarter and more competent than you along multiple dimensions, high temperatures, new wildlife (spiders and wasps), large amounts of water, wobbly platforms and ships, odd shapes and weird objects abundant in the platforms, etc.

This all results in what we might call worldview annealing. That is, the high energy state repeatedly cooled and re-heated over several days enables the fast search over alternate representations of the world. Worldview annealing gives rise to novel ways of seeing the world and one’s relationship with it.* And this is, perhaps, the underlying reason why people report having durable psychological benefits from doing things like attending Burning Man and similar events (see graphs below for statistics about transformative experiences at Burning Man; I intuit that Ephemerisle might be similar in this regard).

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At the end of an event like this, you may very well feel exhausted and totally partied out, but if worldview annealing successfully took place, you will be able to tell that something deep and inward shifted in a good direction. You now have a felt-sense for what a different and better world could be like.

Can such an effect be scaleable? Hopefully many more people can experience it in the future. Perhaps we need to open-source the essential features of that kind of event so that others can take advantage of these key properties and export its benefits elsewhere. And thus we encounter the concept of “Serious Fun”.

Serious Fun

In the last few years I’ve given a lot of thought to the concept of paradise engineering. This comes up a lot when contemplating the coming centuries in light of David Pearce‘s Hedonistic Imperative, which posits that humanity will ultimately get rid of suffering by tackling its genetic roots. Now, it is true that the bulk of what will make our posthuman paradise a paradise is to be found in the quality of experience of our descendants rather than in their external environment. But for our Darwinian minds to contemplate what paradise might look like we usually need to evoke images that give us good feelings in our current state. For example, images of people cooperating to generate incredible experiences! Indeed, saying “in the future we will all be genetically endowed with negligible mu-opioid receptor down-regulation” does not sound nearly as exciting as saying “we will all be incredibly sexy, live our lives in massive cuddle puddles, be on the brink of orgasm, and have mind-blowing levels of intelligence and loving-kindness” (note: the wise would be advised to choose the first option, for the second does not guarantee sustainable happiness while the first one does). To tickle our imagination and inspire motivation it is indeed a good idea to trigger visions that engage our current reward architecture (even if we know that we are responding to Darwinian triggers and that a true paradise has more to do with brain configurations than external conditions).

So let’s think about wonderful external conditions to evoke a sense of paradise. I like to think of large groups of people engaged in serious planning and strategizing to create amazing experiences for even larger groups of people. Burning Man and Ephemerisle are a proof of concept of what could end up becoming super-fun events of civilizational proportions. And here is where we start wondering: what makes such events possible? What is the distribution of effort, time, resources, etc. contributed by each participant that is needed for Serious Fun to take place? My hunch is that to make this work in real life, the distribution needs to have a long-tail:

The Long-Tails of Serious Fun

It is interesting to ponder the idea that the distribution of the total contribution per participant in events like this has a long tail. In the most simplistic case the distribution could be a power law. As it turns out, many phenomena that are usually described with power laws don’t really fit power laws when closely examined.** Now, whether the “true distribution” of the contribution per participant follows a log-normal, ZipfPareto distribution, or one of the general Lévy distributions is an open question. But for the time being, what I want to emphasize is the long-tailed nature of it. In particular, the fact that there seems to be a small cluster of individuals who contribute massively to the event, followed by a larger group that contributes a lot, followed by a large minority who contribute more than they consume, followed by a majority who come to the event and mostly enjoy what others brought with them. Nothing inherently wrong with this, for after all, the people who contribute the most tend to truly enjoy giving, believe in the ideals of the event, and earn the respect of others. That said, it should be noted that if the distribution is too skewed it may lead to burnout among the most active members, which does not bode well for the sustainability of the event.

Although statistics for Ephemerisle are lacking, we can again use as an example people’s responses to the Burning Man Census:

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Burning Man expenses (other than ticket cost). The exact wording of the question in the online survey was, “How much did you spend this year to go to Black Rock City and return, including fuel, camp dues, food, lodging, airfare, supplies, etc. (but not including your ticket to the event)? If you shared expenses with a group, only include the portion of expenses that you contributed. Give your best estimate in USD.” (source)

The above results are represented with too few bins to really be able to tell what kind of long-tail distribution they follows. However, it is pretty clear that we are looking at a very skewed distribution that does not at all look like a normal/Gaussian distribution. I really wish they had included one more option (e.g. $20,000+) so that we could see the number of people who are really (economically) invested in the event. In addition, another key question that would shed light on the long-tailed nature of the event would be “How many hours did you spend preparing/building/helping others/driving/cooking for others/etc.?” Again, I’d expect a very skewed distribution in the responses to such a question.

As we begin to think about how we can plan the creation of heaven worlds (i.e. large-scale projects of fun) we should consider the long-tailed nature of the contribution distribution per participant. My hunch is that we can perhaps determine whether an event is even possible by estimating how skewed the distribution needs to be to make it happen. On one extreme we have events such as “a picnic at the local park” where the event can realistically take place even if most people do roughly the same amount of work (save for perhaps the organizer who post the event details online and coordinate setting up the chairs and coolers). On the other extreme, we could imagine an actual Seasteading event out in the open ocean, or a festival at the very cusp of Mount Diablo, or even something extreme like a party at the Lagrangian between the Earth and the moon, where we would need a group of people to come together and intensely collaborate for many months and spend millions of dollars on providing the basic infrastructure for the event. In-between these two extremes you could find events like community-led concerts, regional Burns, Ephemerisle, and Burning Man proper. Whether a pie-in-the-sky idea like Ephemerisle ever actually gets to happen may be a matter of the event having the right long-tail skew that makes it possible for actual humans to carry it out. In some sense, I suspect that Ephemerisle is right at the edge of impossibility, while Burning Man proper may have more slack and hence can afford to be substantially bigger.

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Lagrangian party?

What other amazing events are there that are “just barely impossible”? And what events will become possible as soon as we discover new techniques, ideologies, and cultural norms to make the distribution needed to make them happen just barely less skewed than impossible? This might be a very generative question to ask if you want to invent “the next Burning Man”.

A final thread to pull here concerns to allometric scaling properties of large events (cf. allometric analysis of Chinese cities). Due to economies of scale, there are thresholds for the number of participants at an event at which some utilities become rentable. Thus, there could also be many un-imagined crazy events that simply require a threshold number of participants to become possible. For example, perhaps a tunnel-based event at a beach is impossible with 100 participants but completely realistic with 500. Who knows! It’s an interesting thing to wonder about.

Anyhow, I invite you to think more about these ideas… perhaps this way you will help us invent the next iteration of paradise on earth.

The End.

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Ephemerisle 2009. Credit: Liz Henry



* This can be used in order to treat the problems associated with psychological adultification. You see, most of the people alive today have some degree of psychological trauma associated with adultification. Acting free and childish is something that we can only really do in a context where we feel like we’ve earned the right to do so. So many highly conscientious people need to nearly kill themselves for the wellbeing of others to feel like they can deserve the right to feel care-free and innocent again. Guess what? Ephemerisle does not have a shortage of ways for you to do prodigious amounts of work to show how much you love others. Hence, perhaps, it is a place where some exceedingly responsible people can finally feel deserving of a relaxed, care-free, time.

** I am using here power laws to point at the general property of long-tailedness. In reality many other similar distributions tend to fit the data better than power laws, among which the log-normal distribution is commonly a superior fit (see: So You Think You Have a Power Law — Well Isn’t That Special?).


Notes:

  1. Featured image source.
  2. I know that the sense of the words idealism and realism in the header quote by Wittgenstein are inappropriate here. I am just amused that the quote happens to be a great fit for this essay if the senses are interpreted within a different context. In true libertarian fashion: Deal with it.

Wada Test + Phenomenal Puzzles: Testing the Independent Consciousness of Individual Brain Hemispheres

by Quintin Frerichs


One of the most pressing problems in philosophy of mind is solving the so-called ‘problem of other minds‘, the difficulty of proving that agents outside oneself have qualia. A workable solution to the problem of other minds would endow us with the ability to define the moral patienthood of present-day biological entities, evade our solipsistic tendencies, and open the door to truly understanding future nonhuman intelligences, should they prove to be conscious. Even more strangely, it would allow us to evaluate whether dream characters or the products of dissociative identity disorder are separate consciousnesses. Irrevocably proving the existence of qualia in other biological life which lacks the capacity for language and higher-order thought is not, to my knowledge, even conceptually feasible at this time. In the case of two agents with the capacity to communicate and problem solve, however, this solution has been proposed, which requires the agent being tested to prove they have qualia by solving a “phenomenal puzzle”. Crucially, the solution does not require that the two agents experience the same qualia, simply that there exists a mapping between their respective conscious states.

If an agent A wishes to prove the existence of qualia in agent B using the above procedure, then A and B must have the following:

  1. A phenomenal bridge (e.g. a biological neural network that connects your brain to someone else’s brain so that both brains now instantiate a single consciousness).
  2. A qualia calibrator (a device that allows you to cycle through many combinations of qualia values quickly so that you can compare the sensory-qualia mappings in both brains and generate a shared vocabulary for qualia values).
  3. A phenomenal puzzle (as described above).
  4. The right set and setting: the use of a proper protocol.

I contend that there may already be a procedure which can be used to generate a reversible phenomenal bridge between two separate minds: a way to make two minds one and subsequently one mind two. Moving in each of these two directions has apparently been demonstrated; by craniopagus twins connected with a thalamic bridge and by corpus callosotomy separating the two cerebral hemispheres. There is tantalizing evidence in each case that consciousness is being fused or fissioned, respectively. In the case of the Hogan sisters, the apparently unitary mind  has access to sensory information from the sensory organs of each cranium. In the case of separating hemispheres there is some debate: alien hand syndrome has suggested the existence of dual consciousness, while other findings have cast doubt on the existence of two separate consciousnesses. While a surgical procedure for separating the hemispheres is as yet permanent, a chemically-induced separation of the hemispheres via the Wada test may provide new avenues for testing the problem of other minds. While some forms of communication (namely language, which is largely left-lateralized) are impaired by the Wada test, other forms such as singing can be left intact. Thus, I believe a combination of Gazzinaga’s procedure and Gómez Emilsson’s phenomenal puzzle approach, in conjunction with a working qualia calibrator, could demonstrate the existence or absence of dual consciousness in the human mind-brain. A version of the Wada test with higher specificity may also be required, to negate some of the characteristic symptoms of confusion, hemineglect, and loss of verbal comprehension.

 

The procedure (utilizing the state space of color, with agents L and R corresponding to the left and right hemispheres) would be as follows: 

Note: a difficulty of utilizing the below outlined procedure is determining which hemisphere should serve as the benchmark. While often language ability is dominant in the left hemisphere (especially in right-handed individuals) and therefore eliminated when the left hemisphere is inactivated during the Wada test, this is not always the case. In cases where at least some language ability is preserved in each hemisphere, either can reliably serve as the point of comparison. 

  1. Design a phenomenal puzzle, such that the solution corresponds to reporting the number of just noticeable differences required to produce a linear mapping between two locations in the state space of color. 
  2. Separate the left and right visual fields (Gazzaniga).
  3. Sodium amobarbital is administered to the left internal cardioid artery via the femoral artery and EEG confirms inactivation of the left hemisphere. In the LVF a consent checkbox for performing the experiment is given to the right hemisphere, Y/N checked using the left hand.
  4. Similarly, sodium amobarbital is administered to the right internal cardioid artery via the femoral artery and EEG confirms inactivation of the right hemisphere. Consent can be verbally obtained from the left hemisphere. 
  5. With both hemispheres activated, qualia calibration on the state space of color is performed (see: A workable solution to the problem of other minds). 
  6. With R inactivated, the phenomenal puzzle is presented to L without enough time for L to solve the puzzle.
  7. Both hemispheres are activated, and L tells the phenomenal puzzle to LR.
  8. L is inactivated and R attempts to solve the puzzle on its own. When R claims to have solved the puzzle (in writing or song most likely), both hemispheres are again reactivated in order to produce LR. R shares its solution with LR.
  9. R is inactivated, and L shares the solution to the phenomenal puzzle. If the solution is correct, then R is conscious! 

Point-of-view characterization of above procedure (Under the assumption that both hemispheres are, in fact, conscious):

  1. From the perspective of the left brain: A researcher asks “do you consent to the following procedure?” You answer ‘yes’, perhaps wondering if you’ve lost just a part of your computational resources, or created an entirely separate consciousness. A short period of darkness and sedation ensues while consent is obtained from the right brain. Suddenly, the amount of consciousness you’re experiencing expands greatly and new memories are available. The computer screen in front of you rapidly cycles through a series of paired color values. The Qualia Calibrator confirms a match by waiting for consensus of the right motor cortex (in lieu of a button press) and from verbal confirmation of the left hemisphere. It feels like an eye exam at hyper speed: “Color one or color two? Color two or color three?”, but for thousands of colors, many of which you don’t have a name for. Then, you sleep, for some indeterminate amount of time. When you awaken, the researcher explains to you the puzzle to solve. Your consciousness is then expanded again, and you repeat the puzzle to yourself, with the strange feeling that “part of you didn’t know about it”. You go dark again. And when the lights are turn on again, things feel normal, but you have a prominent new memory, the solution to the puzzle. Quickly you check. Take this strange shade of cyan and change it once, twice, three times…yup! That’s the mellow orange you were looking for, and in the same number of “just noticeable differences”.
  2. From the perspective of the right brain: You awaken to a scrollable consent form with a checkbox, and a left-handed mouse. Despite your state of relative confusion and lack of verbal fluency, you’re able to understand the form and check the box. Suddenly, your conscious experience expands and your fluency erupts. The computer screen in front of you rapidly cycles through a series of paired color values. The Qualia Calibrator confirms a match by waiting for consensus of the right motor cortex (in lieu of a button press) and from verbal confirmation of the left hemisphere. It feels like an eye exam at hyper speed: “Color one or color two? Color two or color three?”, but for thousands of colors, many of which you don’t have a name for. Again you sleep, your consciousness is briefly expanded, and you learn of the puzzle you are to solve. How did you learn about it? It is weird, you started “repeating” the puzzle to yourself, with the strange feeling that “part of you already had heard it before”. But either way, now you feel like you have heard it really well. Next, it feels like you took a strong sedative and a memory-loss drug at the same time. Now, in this highly impoverished cognitive state, you have to solve a complicated puzzle. To prove that you exist. Ugh. Fortunately, you have help, in the form of an AI which provides the linear mapping you need to discover, provided you answer how many just noticeable differences occur between each set of two points. Half man and machine collaborate to find the solution, and you commit it to memory. Reunited once more, you “share your findings to yourself”. It turns out you’re conscious. The world now knows: the right hemisphere is conscious on its own when the left one is unconscious. Hooray!