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

Harmonic Society (4/4): Art as Valence Modulation and Future Affective Language

The following essay* was recently published in the Berlin-based art magazine Art Against Art (buy issue).

The essay offers eight different models of art: models 1 through 4 have been discussed in academic literature and the current intellectual zeitgeist, while models 5 through 8 are new, original, and the direct result of recent insights about consciousness as uncovered by modern neuroscience, philosophy of mind, and the work of the Qualia Research Institute.

Below you will find models 7 and 8, which conclude this series of posts. (See previous models: 1 & 2, 3 & 4, and 5 & 6).


7. Valence Modulation

What is the difference between indifference and interest, boredom and thrill, despair and bliss? Pleasure! A few grains of this magic ingredient are dearer than a king’s treasure, and we have it a plenty here in Utopia. It pervades into everything we do and everything we experience. We sprinkle it in our tea.

The universe is cold. Fun is the fire that melts the blocks of hardship and creates a bubbling celebration of life.

It is the birth right of every creature, a right no less sacred for having been trampled upon since the beginning of time.
Letter From Utopia by Nick Bostrom

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Photo by Andrés Silva (aka. El Capitán). Claudia Silva (in the picture).

We are now approaching the point at which we will finally start cooking with peanut oil, so to speak. We will finally start thinking about how to build extremely good art from first principles. The ‘Art as Valence Modulation’ model builds on top of the previous model where art involves messing with the brain’s energy parameter. To explain this model we need to introduce two additional concepts:

  1. Neural Annealing, and
  2. The Symmetry Theory of Valence (STV)

Neural annealing is a concept we developed at QRI to extend the entropic disintegration framework.[1] Namely, the most beneficial use of ‘energy’ is to direct it towards the brain’s natural harmonics in order to carve out the presence of a naturally blissful state in everyday life. This process works on a progression that goes like this:

  1. Energy application
  2. Entropic disintegration
  3. Search/self-reorganization
  4. Neural annealing

Together with neural annealing, STV provides an answer for why we experience intensely rewarding states of consciousness from art. Here is where some of the theories that we have been working on come into play. In particular, we hypothesize that when highly-energized states of consciousness follow an adequate cooling schedule, they can give rise to highly ordered states that are experienced as very pleasant and which can carve good attractor states into the brain in the long term. Making an analogy with metallurgy, with annealing, you can increase the regularity of the microscopic structure of metal by heating it above the recrystallization temperature and letting it cool. This results in changed material properties (such as reduced hardness and increased ductility). We hypothesize that something along these lines also takes place in brains. Neural annealing facilitates solving complex constraint satisfaction problems at the perceptual, emotional, and conceptual level. The higher energy enables quick search between possible configurations that satisfy as many constraints as possible (over- stepping the local maxima we are usually stuck within normal energy ranges), while the cooling process solidifies the best constraint satisfaction solutions. Critically, here the STV comes into play by proposing that the more regular the resulting neural structures are, the better they feel. Annealing smooths out inconsistencies and irregularities, which according to the STV are key sources of discomfort. Symmetry, in the form of smoothness and harmony, is why the process of annealing leaves you feeling great.

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Very high-valence annealed states of mind feel cosmic and profound in significance. Images by Adrián Regnier Chávez

In this light, art with lasting desirable mood effects does not only need to increase the energy parameter, but it also needs to know how to lower it at the right schedule in order to leave people annealed to a given desirable mindset. A lot of art that successfully raises the energy parameter nonetheless does not succeed in the ecosystem of human attention, because it does not let people cool off in the right way. More so, an excessively competitive memetic landscape that incentivizes maximum surprise tends to train people to experience too much fear of missing out to let them adequately consume art at the pace needed to leave you better off emotionally. There is genuine wisdom in going to museums with one’s smartphone turned off.

Where do we draw the line between healthy recreation and distraction? Some might say that art in the form of pictures is fine, but audiovisual is too much. Some may be fine with movies but not with VR. Others would be ok with videogames but perhaps not with drugs. Others perhaps would be ok with drugs but not with genetic modification of neuronal gene expression. Some would be ok with that but not with neural dust rewiring, and so on. The format, we would argue, is not what matters. But rather, what the annealing pattern is, which is actually what makes the effects of art stick in the long run (or not).

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Image by Joseph Matthias Young. It makes me think of the aesthetic of the meta-aesthetic.

This way of seeing art is highly generative. It gives us a research lead for how to construct new grandiose and highly-effective art. More so, the model can itself be developed as an aesthetic of its own. Perhaps we could call it the aesthetic of the meta-aesthetic. That is, an aesthetic that rewards distilling the essential reason why any aesthetic can feel good and meaningful. In the future, we might expect to see in stores “Hedonium Magazine” – which catalogues all of the peak-valence states that can be achieved with any method whatsoever, and sees the craft of perfecting neural annealing as itself the highest form of art. Here we transcend the post-modern ethos of giving each aesthetic its place in the garden of paradoxes. Yes, give each aesthetic its place, but do not let that prevent you from building a meta- narrative that ties together and clarifies the value-add of each aesthetic. No aesthetic is above being examined in terms of how it achieves neural annealing in those who consume it.

In turn, this model gives us a new understanding of what an “aesthetic” even is. According to it, an aesthetic is a system for long-term neural annealing. A one-off weird art piece might give rise to annealing and solidify random structures in your brain. An aesthetic is more than that. It is a collection of generator seeds for art pieces that give rise to a coherent form of neural annealing that is reinforced with each piece, no matter how different they may seem from one another on the surface.

A further property of neural annealing is that it is what enables you to fully experience a self-consistent worldview as if true. This bridges the gap between meaning and pleasure, and is at the core of the connection between valence and the experience of sacredness we discussed in model 4. According to model 7, sacred experiences are the result of driving the energy parameter of the brain above the recrystallization threshold and then having it cool down as it reorganizes the elements of a given target ontology and worldview. The result is an annealed mental state optimized to represent that worldview. The sense of global consistency makes the worldview feel good and true, almost as if you were able to smell truth with it. This model would say, thus, that the core mechanism behind every kind of sacred experience is the same. Which emotions, ontologies, and worldviews get annealed is what is different depending on set, setting, and aesthetic (i.e. how the energy sources and sinks were modified). But deep down, it is successful annealing that makes sacred experiences feel so compelling and good.

8. Affective Language: Harmonic Society

An idealised full-spectrum superintelligence will indeed be capable of an impartial “view from nowhere” or God’s-eye-view of the multiverse, a mathematically complete Theory Of Everything – as does modern theoretical physics, in aspiration if not achievement. But in virtue of its God’s-eye-view, full-spectrum superintelligence must also be hypersocial and supersentient: able to understand all possible first-person perspectives, the state-space of all possible minds in other Hubble volumes, other branches of the universal wavefunction (UWF) – and in other solar systems and galaxies if such beings exist within our cosmological horizon. Idealized at least, full-spectrum superintelligence will be able to understand and weigh the significance of all possible modes of experience irrespective of whether they have hitherto been recruited for information-signalling purposes.
David Pearce, in The Biointelligence Explosion (2012)

If we succeed at developing a science of art built on top of a modern science of consciousness, what should we do with it? What would the art of a wise post-scarcity and post-suffering society look like? As far I can tell, Utopia consists of both having the system in place to keep the lights on, while being able to use the surplus energy to power blissful experiences beyond the bounds of our current conceptions.

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Harmonic Society by ALGE

The vision of Harmonic Society is that of a particular type of post-suffering utopia that resolves to optimize for good art. Referencing the models of art we’ve built upon so far: Harmonic Society (1) knows there are stakes in art and hence sidesteps the traps of semantic deflation, (2) avoids runaway signaling and Cool Kid gridlock, (3) utilizes Hipsters to explore promising new frontiers, (4) has mastery over a diverse range of conceptions of the sacred, (5) systematically explores the state-space of consciousness, (6) has a scientific and precise understanding of the energy parameter of experience, and (7) has deep knowledge of how to induce arbitrary types of neural annealing. In addition to all of this, Harmonic Society has (8) a map of all high-level aesthetics, knows what they are useful for, and can instantiate them at will.

In Harmonic Society there is always a way to smoothly transition between seemingly irreconcilable aesthetics. It deeply understands the pros and cons of different aesthetics and knows how to apply them optimally both for instrumental purposes and hedonic value.

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Image by Michael Aaron Coleman

Nowadays a lot of people who could benefit from, e.g. going to art festivals, taking acid, subpack cuddle parties, participating in plays (i.e. exposing themselves to high-end aesthetic experiences), find it hard to do so, because it is difficult to get back to work once the weekend is over after experiencing incredible bliss. A rough solution to avoid residual incompatibility between the state you annealed over on the weekend with the mindset you need today for work would be to develop a mood organ[2] that instantly puts you into any mindset you want. But perhaps a more elegant solution is to have such an advanced and detailed map of the state-space of mindsets that smooth, painless, and synergistic transitory states between arbitrary modes of being are discovered.

Thus, one could one minute be on a 5-MeO-DMT-type white light conscious void ultra-blissful state, the next minute be on a perfectly functional MDMA-like state useful for socializing, the minute after moving to a highly-focused nootropic-like systematizing state, and so on. The aesthetic to foster here is a meta-aesthetic of avoiding sharp discontinuities between mindsets, and allowing you to transition between all known awesome aesthetics. In Harmonic Society the entire state-space of consciousness is your oyster.

A further thought about Harmonic Society is that a sufficiently advanced understanding of aesthetic experience might even revolutionize our understanding of identity.
For instance, a non-trivial sense of personal diachronic identity could arise if everyone
starts to identify with e.g. a different person-specific song. If we truly understood how
valence works and we had full access to our neurocircuitry, we could in a way embody a
given work of art and interact with others in a way that is consistent with the artistic
degrees of freedom our identity allows. This way, people’s interactions could perhaps be guaranteed to be positive. The combinatorial space of possible back-and-forth interactions does not need to be small, since high-energy allows for incredibly varied states. But nonetheless we could get to a point of understanding how valence works such that we could provably demonstrate that two persons with the right neural implementations will always have positive-sum interactions no matter what.

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Identity in Harmonic Society: The aesthetic of understanding the valence of every possible state of consciousness and how to translate what matters between them. (Picture: Symbol of Open, Empty, Closed Individualism from Burning Man Theme-Camps of the Year 2029, Continuity Camp)

Conclusion

As the guiding premise of this essay we started out assuming that there are real and substantial stakes in art. It sure is all fun and games to think that anything goes in art until your landscape of cultural meaning is polluted with replicator strategies and attention-zapping exploits that lead to long-term neuropsychological problems and anneal false and neurotic metaphysics. Understanding art matters.

I would make the claim that a new science of valence, i.e. a new science of pleasure, pain, love, hate, and indeed transcendent bliss, can be a new rallying flag for cultural value. Rather than the messy consilience patchwork between different aesthetics we have today, we might in the future indeed find a true and real grounding for the meaning of beauty and bliss. Contrary to the conservative spirit often associated with calls to reinvigorate an objective sense of beauty, here we arrive at a theory of art that would very well appreciate experiences as outlandish as DMT breakthroughs. This theory of art appreciates such states not “just as much” as fine art, but indeed as far more valuable and implicated in what matters than most of everyday life. For art, meditation, psychedelics, and philosophy all share the fact that they are messing with the energy parameter of experience in powerful ways that can be used to achieve much better and globally-consistent brain states. Understanding that the effects of art can be very strong and life-changing is one thing, but knowing the mechanism of action behind those changes comes with entirely new possibilities and responsibilities. We invite you to consider what this entails, and to join us in envisioning a future Harmonic Society constructed with full knowledge of neural annealing.


[1] It is worth mentioning that Steven Lehar used annealing to describe the subjective progression of his ketamine experiences in his book The Grand Illusion: A Psychonautical Odyssey Into the Depths of Human Experience. [October 2019 – Edit: Carhart-Harris and Friston wrote a paper together in which they discussed annealing in the context of psychedelic research (see summary). The paper was published in July, two months after I submitted this essay to Art Against Art in May of 2019. We are delighted to see independent convergence on this concept and its importance.]

[2] The Penfield Mood Organ is a technology described in Do Androids Dream of Electric Sheep? by Philip K. Dick that allows the user to instantly tune into any of hundreds of possible moods via direct cerebral stimulation. Some example moods include “3. The desire to dial other moods”, “481. Awareness of the manifold possibilities open to me in the future”, “594. Pleased acknowledgment of husband’s superior wisdom in all matters”, and “888. The desire to watch TV, no matter what’s on it”.



Glossary

Cool Kids: Someone who is well-rounded and uses strategic mediocrity in order to entice people to show their peacock feathers. At its extreme, Cool Kids become the leaders of artistic gangs who corner the marketplace of aesthetic attention.

Hipster: Someone who enjoys art and media that seems too obscure to care about. Typically, the preferred aesthetics of a Hipster are highly detailed and focus on specific favored attributes at the expense of well-roundedness. A Hipster does not only have opinions about what is enjoyable, but also about how to enjoy it and why.

Nerd: Someone who wants to figure out what is true, especially as it applies to technical and formal systems. A philosophy nerd, for instance, compulsively tries to figure out ultimate truth.

Minimax art strategies: A strategy for making art that tries to be the best on a narrow set of attributes while neglecting well-roundedness. This is sometimes adaptive and some- times maladaptive.

L1/L2 normalization: Using mean absolute error (L1) favors minimax strategies vs. using mean squared error (L2) which favors well-rounded strategies.



Special thanks to: Michael Johnson, Romeo Stevens, Liam Brereton, Duncan Wilson, Victor Ochikubo, and David Pearce for their thoughts and feedback.



* The full essay’s title is: Harmonic Society: 8 Models of Art for a Scientific Paradigm of Aesthetic Qualia

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The Psychobiology of Subcultures

Evolutionary qualia suggests our inner world-simulations are not merely painted with different colors, but have different soundtracks, aesthetics, narrative themes, and walk-on character status. Cilantro tasting like soap to ~10% of people is merely the canary in the coal-mine. Our differences in qualia (and consciousness more broadly) probably involve modes of experience you and I don’t even know exist.


Excerpt from Global Brain (2000) by Howard Bloom (Pgs. 143 – 146). [Emphasis mine]

Our brains differ as much as our bodies. Indeed, they may differ more. One part of the brain, the anterior commissure […] varies seven-fold in area between one person and the next. Another part, the massa intermedia […], is not found at all in one in four people. The primary visual cortex can vary three-fold in area. Something called our amygdala (it is responsible for our fears and loves) can vary two-fold in volume – as can something called our hippocampus (involved in memory). Most surprisingly, our cerebral cortex varies in non-learning impaired people nearly two-fold in volume.

 

– Dr. John Robert Skoyles

Thanks to Plato, we have what purport to be records of the conversations of a human Cuisinart of concepts, an eclectic sage whose roughly fifty-year-long intellectual life bracketed the Periclean Golden Age (443-429 B.C.). This all-purpose conceptual chopper and blender was that son of a socially high-placed family, Socrates. Experts and neophytes agree that it’s impossible to tell how many of the words Plato ascribes to this self-appointed gadfly were authentic and how many were simply Plato’s way of getting his own notions into the public eye. But one thing is generally accepted as accurate – the names of the folks from whom Socrates extracted opinions before shredding them with the quiz mastering which now bears his name (Socratic dialogue). The cast of characters palavering with Socrates in Plato’s Dialogs, says learned reasoning, was too well known in Athens for Plato to have fudged.

Just who were the fonts of learned conversation whose wisdom Socrates whipped and whirled? Socrates’ interlocutors were frequently famous thinkers from distant cities, each of which specialized in a different manner of plucking goods from its surroundings and injecting them into the circulatory system through which the trade of the Mediterranean and the Black Sea swirled. Socrates was a student of Anaxagoras, who came from the Ionian city of Clazomenae on the coast of today’s Turkey. He was also a disciple of Archelaus, another Ionian import. The Socratic dialogues Plato “chronicled” included those with Protagoras from the Balkan city of Abdera, Hippias from Peloponnesian Elis, Parmenides from Italy’s Elea, and Gorgias from Sicily’s Leontini. Each visiting intellect had been shaped by contact with a unique group of surrounding tribes, and by the exigencies imposed on city structure, domestic habit, and vested interest by distinctive forms of enterprise. One result: each arrival presented a philosophy which appealed to a very different configuration of the human mind.

To understand how philosophy couples with the mind’s biology, let’s track the complex adaptive system’s best-concealed constituent to its hiding place. The five elements of the complex adaptive system are conformity enforcers, diversity generators, inner-judges, resources shifters, and intergroup tournaments. Inner-judges may be the most unusual of the crew, for they are physiological built-ins which work deep inside the body to transform a bacterium, a lizard, a baboon, a me, or a you into a module of a larger learning machine. The basic rule of learning machines is one we’ve already seen: turn on the juice to components which have a grip on the problem at hand and turn off the power to those components which just can’t seem to understand. Inner-judges help decide whether the components in which they reside will be enriched or will be denied, then they aid in carrying out the sentence. The irony is that these evaluators, prize givers, and executioners are built into their victims biologically. On the microlevel, inner-judges work through “programmed cell death” – apoptosis – a molecular chain reaction deep within the genes which ends in cellular suicide. In higher animals the inner-judges dole out interior punishments which range from overdoses of stress hormones to emotional miseries. Or they grant internal bonuses of zest and confidence to those of us fulfilling our group’s needs.

When we feel like kicking ourselves around the block or curling up and disappearing, our condemnation comes from inner-judges like guilt and shame. What’s a good deal harder to realize is that behind the scenes our inner-judges sicken us and dumb us down quite literally. If they sense we’re a drag on the collective intelligence, inner-judges down shift our immune system and neurochemically cloud our ability to perceive. They induce a narcotic haze by swamping our system with endorphins, the body’s self-produced equivalent of morphine*. And they flood us with glucocorticoids which kill off both brain cells and lymphocytes – critical cells in our fight against disease.

Inner-judges measure our contribution to the social learning machine by two yardsticks: (1) our personal sense of mastery; and (2) the hints we get from those around us telling us whether they want us eagerly or couldn’t care less if we disappeared like a blackhead from the face of decent society.

Mastery is a useful gauge. It measures whether we’re coping with the trials tossed our way, and whether our example can help steer others in their trip through choppy seas. Popularity is an equally practical yardstick. It measures the extent to which we’re feeding others’ physical, organizational, and/or emotional needs.

Nestled deep within our neuroendocrine complex, inner-judges operate on a sliding scale. By adjusting our mix of neurotransmitters like serotonin, dopamine, norepinephrine, and acetylcholine, or the balance between the gloomy right and sunny left side of the brain, they shift us from fear to daring, from misery to happiness, from grouchiness to charm, from timid silence to expansive speech, from deflation to elation, from pain to ecstasy, from confusion to insight, and from listlessness to lust or to the resolute pursuit of goals.

Some of us are born with inner-judges whose verdicts are perpetually harsh. The result is depression, shyness, and heightened susceptibility to pain. Others arrive from the womb with inner-judges preset to treat us generously, endowing us with energy, few inhibitions, a deep sense of security, and little sense of guilt or shame. But most of us are in the middle – our inner-judges sentence us sternly or magnanimously depending on the snugness with which we fit our social network’s needs.

Those born with inner-judges excessively lenient or severe have taught us much about the secrets of mental and emotional diversity. Harvard University researcher Jerome Kagan has probably never heard the term “inner-judges,” yet he may have done more than any other psychologist to uncover their capabilities. To understand what Kagan hath wrought, a background briefing is in order.

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The early-twentieth-century psychoanalytic thinker Carl Jung, says Kagan, originated the concept of introverted and extroverted personalities. Jung also believed that each had a slightly different brain structure. Kagan feels that in his own way, he has proven Jung right. He’s found that 10 to 15 percent of infants are born with a tendency to be fearful and withdrawn, while another 10 to 15 percent are born with a flair for dauntless spontaneity. During the last few decades of the twentieth century, Kagan performed numerous experiments and accumulated large amounts of data demonstrating his concept’s validity.

He refers to facts like these:

  • In studies of Japanese and American newborns, some infants took the removal of the nipple from their mouths calmly, while others went into emotional fits. The babies as yet had had no opportunity to learn these reactions from their parents. The tendencies were those they’d brought with them from the isolation of the uterus. At fourteen months, the babies who’d been easily upset at birth were still so oversensitive that they often broke out crying when the sight of a stranger loomed. On another test, babies who became upset at birth when they were switched suddenly from water to a sugar solution squalled hysterically at the age of one or two when their mothers left the room, but babies who had taken the change in beverage casually did not. In addition, a study of 113 children showed that those who had a hard time handling the unexpected when they were one year old were still shy and withdrawn by the time they reached six.
  • This tendency toward variation in personality was not limited to human beings. According to Kagan, it appeared in dogs, mice, rats, wolves, cats, cows, monkeys, and paradise fish. Some of these animals were fascinated by novelty. Others were terrified by anything the least bit out of place.
  • Fifteen percent of cats steered clear of strangers and even avoided attacking rats. This was remarkably close to the percentage of humans frozen by anxiety attacks.

Kagan traces these differences to genes, which can help set off a lifelong domino effect in the brain. The production of key manufacturing enzyme for the stimulant norepinephrine, says Kagan, is controlled by a single pair of genes, making norepinephrine levels highly heritable. Norepinephrine – which is also a potent stress hormone – shows up very early in the development of the embryo, making the hippocampus oversensitive to the unfamiliar, and hyperactivating the amygdala, which jolts us with the warning signal we call fear. The hippocampus and amygdala – as we’ve seen earlier – are central shapers of the memory bank we call reality. They are also key to the inner-judges’ machinery.

[…]

Later in life the products of a prebirth norepinephrine cascade are timid children, who, in carefully controlled studies, are alert to slight changes in tones or brightness of light that other children miss. In other words, these children literally see and hear their world in ways others would not recognize. According to Kagan, the constitutionally frightened are endowed with a limbic system hair-triggered to curse them with a sense of imminent catastrophe. As a consequence, shy children attempt to escape punishment by hiding from everyday events which threaten to torment them hideously. Uninhibited children, on the opposite end of the scale, have underaroused limbic systems and demand a deluge of entertainment to dodge boredom’s intolerability. Their craving for excitement can sometimes wear their parents to a frazzle.

Kagan’s shy children are condemned to solitude and pain by hanging judges in their own biology. Kagan’s uninhibited kids are gifted with indulgent inner-judges predisposed by the limbic system to offer such unearned rewards as boldness and social dexterity. But most of the animals and humans Kagan has studied avoid these two extremes. Seventy percent remain in the middle, their inner-judges handing out positive and negative verdicts according to the rules of the learning machine.fflkm4309e031


*”Endorphin” is a contraption of the term “endogenous morphine.



See also:

Announcement: QRI Presentations at Harvard and NYU

The Qualia Research Institute is in Boston for the month of September.

Yesterday I gave a presentation about the Logarithmic Scales of Pleasure and Pain at the Harvard Effective Altruism student group (video coming soon! – slides).

I will be giving a presentation about The Hyperbolic Geometry of DMT Experiences at the Harvard Science of Psychedelics Club on September 17, at 8pm (Sever 113). The venue is apparently quite large so we are not going to run out of capacity for this talk. Feel free to amplify this as a Schelling point for smart rational psychonauts to meet one another.

Michael Johnson will also be giving a presentation at the Harvard Science of Psychedelics Club: 21st of September (7PM), at the Fong Auditorium in Boylston Hall.

Finally, I’ll be giving a presentation at Effective Altruism NYC (also about Logarithmic Scales) on September 23rd (7PM), at 334 E 30th St #3. See: facebook event.

Both Harvard talks are free and open to the public. The venues have a large number of seating spots, so all you need to do is show up. For the NYU talk the organizers of the event would like you to get a (free) ticket first in order to RSVP and secure a seat as the venue is not very large.

We will record these talks, share them online, and add them to the list of media appearances.

 


 

If you are in Boston, want to meet up with us, but can’t make it to any of the talks: I will show up to the SSC meetup on the 20th of September wearing a Qualia Research Institute shirt. Feel free to find me and say hi.


Many thanks to: Andrew Zuckerman, Kenneth Shinozuka, Jacob Shwartz-Lucas, and
Anisha Zaveri for organizing these events!

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.

Does Full-Spectrum Superintelligence Entail Benevolence?

Excerpt from: The Biointelligence Explosion by David Pearce


The God-like perspective-taking faculty of a full-spectrum superintelligence doesn’t entail distinctively human-friendliness any more than a God-like superintelligence could promote distinctively Aryan-friendliness. Indeed it’s unclear how benevolent superintelligence could want omnivorous killer apes in our current guise to walk the Earth in any shape or form. But is there any connection at all between benevolence and intelligence? Pre-reflectively, benevolence and intelligence are orthogonal concepts. There’s nothing obviously incoherent about a malevolent God or a malevolent – or at least a callously indifferent – Superintelligence. Thus a sceptic might argue that there is no link whatsoever between benevolence – on the face of it a mere personality variable – and enhanced intellect. After all, some sociopaths score highly on our [autistic, mind-blind] IQ tests. Sociopaths know that their victims suffer. They just don’t care.

However, what’s critical in evaluating cognitive ability is a criterion of representational adequacy. Representation is not an all-or-nothing phenomenon; it varies in functional degree. More specifically here, the cognitive capacity to represent the formal properties of mind differs from the cognitive capacity to represent the subjective properties of mind. Thus a notional zombie Hyper-Autist robot running a symbolic AI program on an ultrapowerful digital computer with a classical von Neumann architecture may be beneficent or maleficent in its behaviour toward sentient beings. By its very nature, it can’t know or care. Most starkly, the zombie Hyper-Autist might be programmed to convert the world’s matter and energy into heavenly “utilitronium” or diabolical “dolorium” without the slightest insight into the significance of what it was doing. This kind of scenario is at least a notional risk of creating insentient Hyper-Autists endowed with mere formal utility functions rather than hyper-sentient full-spectrum superintelligence. By contrast, full-spectrum superintelligence does care in virtue of its full-spectrum representational capacities – a bias-free generalisation of the superior perspective-taking, “mind-reading” capabilities that enabled humans to become the cognitively dominant species on the planet. Full-spectrum superintelligence, if equipped with the posthuman cognitive generalisation of mirror-touch synaesthesia, understands your thoughts, your feelings and your egocentric perspective better than you do yourself.

Could there arise “evil” mirror-touch synaesthetes? In one sense, no. You can’t go around wantonly hurting other sentient beings if you feel their pain as your own. Full-spectrum intelligence is friendly intelligence. But in another sense yes, insofar as primitive mirror-touch synaesthetes are prey to species-specific cognitive limitations that prevent them acting rationally to maximise the well-being of all sentience. Full-spectrum superintelligences would lack those computational limitations in virtue of their full cognitive competence in understanding both the subjective and the formal properties of mind. Perhaps full-spectrum superintelligences might optimise your matter and energy into a blissful smart angel; but they couldn’t wantonly hurt you, whether by neglect or design.

More practically today, a cognitively superior analogue of natural mirror-touch synaesthesia should soon be feasible with reciprocal neuroscanning technology – a kind of naturalised telepathy. At first blush, mutual telepathic understanding sounds a panacea for ignorance and egotism alike. An exponential growth of shared telepathic understanding might safeguard against global catastrophe born of mutual incomprehension and WMD. As the poet Henry Wadsworth Longfellow observed, “If we could read the secret history of our enemies, we should find in each life sorrow and suffering enough to disarm all hostility.” Maybe so. The problem here, as advocates of Radical Honesty soon discover, is that many Darwinian thoughts scarcely promote friendliness if shared: they are often ill-natured, unedifying and unsuitable for public consumption. Thus unless perpetually “loved-up” on MDMA or its long-acting equivalents, most of us would find mutual mind-reading a traumatic ordeal. Human society and most personal relationships would collapse in acrimony rather than blossom. Either way, our human incapacity fully to understand the first-person point of view of other sentient beings isn’t just a moral failing or a personality variable; it’s an epistemic limitation, an intellectual failure to grasp an objective feature of the natural world. Even “normal” people share with sociopaths this fitness-enhancing cognitive deficit. By posthuman criteria, perhaps we’re all quasi-sociopaths. The egocentric delusion (i.e. that the world centres on one’s existence) is genetically adaptive and strongly selected for over hundreds of millions of years. Fortunately, it’s a cognitive failing amenable to technical fixes and eventually a cure: full-spectrum superintelligence. The devil is in the details, or rather the genetic source code.


(Featured Image: Source)

Logarithmic Scales of Pleasure and Pain: Rating, Ranking, and Comparing Peak Experiences Suggest the Existence of Long Tails for Bliss and Suffering

TL;DR

Based on: the characteristic distribution of neural activity, personal accounts of intense pleasure and pain, the way various pain scales have been described by their creators, and the results of a pilot study we conducted which ranks, rates, and compares the hedonic quality of extreme experiences, we suggest that the best way to interpret pleasure and pain scales is by thinking of them as logarithmic compressions of what is truly a long-tail. The most intense pains are orders of magnitude more awful than mild pains (and symmetrically for pleasure).

This should inform the way we prioritize altruistic interventions and plan for a better future. Since the bulk of suffering is concentrated in a small percentage of experiences, focusing our efforts on preventing cases of intense suffering likely dominates most utilitarian calculations.

An important pragmatic takeaway from this article is that if one is trying to select an effective career path, as a heuristic it would be good to take into account how one’s efforts would cash out in the prevention of extreme suffering (see: Hell-Index), rather than just QALYs and wellness indices that ignore the long-tail. Of particular note as promising Effective Altruist careers, we would highlight working directly to develop remedies for specific, extremely painful experiences. Finding scalable treatments for migraines, kidney stones, childbirth, cluster headaches, CRPS, and fibromyalgia may be extremely high-impact (cf. Treating Cluster Headaches and Migraines Using N,N-DMT and Other Tryptamines, Using Ibogaine to Create Friendlier Opioids, and Frequency Specific Microcurrent for Kidney-Stone Pain). More research efforts into identifying and quantifying intense suffering currently unaddressed would also be extremely helpful. Finally, if the positive valence scale also has a long-tail, focusing one’s career in developing bliss technologies may pay-off in surprisingly good ways (whereby you may stumble on methods to generate high-valence healing experiences which are orders of magnitude better than you thought were possible).

Contents

Introduction:

  1. Weber’s Law
  2. Why This Matters

General ideas:

  1. The Non-Linearity of Pleasure and Pain
    1. Personal Accounts
    2. Consciousness Expansion
    3. Peak Pleasure States: Jhanas and Temporal Lobe Seizures
    4. Logarithmic Pain Scales: Stings, Peppers, and Cluster Headaches
  2. Deference-type Approaches for Experience Ranking
    1. Normal World vs. Lognormal World
    2. Predictions of Lognormal World

Survey setup:

  1. Mechanical Turk
  2. Participant Composition
  3. Filtering Bots

Results:

  1. Appearance Base Rates
  2. Average Ratings
  3. Deference Graph of Top Experiences
    1. Rebalanced Smoothed Proportion
    2. Triadic Analysis
  4. Latent Trait Ratings
  5. Long-tails in the Responses to “How Many Times Better/Worse” Question

Discussion:

  1. Key Pleasures Surfaced
    1. Birth of Children
    2. Falling in Love
    3. Travel/Vacation
    4. MDMA/LSD/Psilocybin
    5. Games of Chance Earnings
  2. Key Pains
    1. Kidney Stones/Migraines
    2. Childbirth
    3. Car Accidents
    4. Death of Father and Mother
  3. Future Directions for Methodological Approaches
    1. Graphical Models with Log-Normal Priors
  4. Closing Thoughts on the Valence Scale
  5. Additional Material
    1. Dimensionality of Pleasure and Pain
    2. Mixed States
    3. Qualia Formalism
  6. Notes

Introduction

Weber’s Law

Weber’s Law describes the relationship between the physical intensity of a stimulus and the reported subjective intensity of perceiving it. For example, it describes the relationship between how loud a sound is and how loud it is perceived as. In the general case, Weber’s Law indicates that one needs to vary the stimulus intensity by a multiplicative fraction (called “Weber’s fraction”) in order to detect a just noticeable difference. For example, if you cannot detect the differences between objects weighing 100 grams to 105 grams, then you will also not be able to detect the differences between objects weighing 200 grams to 210 grams (implying the Weber fraction for weight perception is at least 5%). In the general case, the senses detect differences logarithmically.

There are two compelling stories for interpreting this law:

In the first story, it is the low-level processing of the senses which do the logarithmic mapping. The senses “compress” the intensity of the stimulation and send a “linearized” packet of information to one’s brain, which is then rendered linearly in one’s experience.

In the second story, the senses, within the window of adaptation, do a fine job of translating (somewhat) faithfully the actual intensity of the stimulus, which then gets rendered in our experience. Our inability to detect small absolute differences between intense stimuli is not because we are not rendering such differences, but because Weber’s law applies to the very intensity of experience. In other words, the properties of one’s experience could follow a long-tail distribution, but our ability to accurately point out differences between the properties of experiences is proportional to their intensity.

We claim that, at least for the case of valence (i.e the pleasure-pain axis), the second story is much closer to the truth than the first. Accordingly, this article rethinks the pleasure-pain axis (also called the valence scale) by providing evidence, arguments, and datapoints to support the idea that how good or bad experiences feel follows a long-tail distribution.

As an intuition pump for what is to follow, we would like to highlight the empirical finding that brain activity follows a long-tail distribution (see: Statistical Analyses Support Power Law Distributions Found in Neuronal Avalanches, and Logarithmic Distributions Prove that Intrinsic Learning is Hebbian). The story where the “true valence scale” is a logarithmic compression is entirely consistent with the empirical long-tails of neural activity (in which “neural avalanches” account for a large fraction of overall brain activity).

The concrete line of argument we will present is based on the following:

  1. Phenomenological accounts of intense pleasure and pain (w/ accounts of phenomenal time and space expansion),
  2. The way in which pain scales are described by those who developed them, and
  3. The analytic results of a pilot study we conducted which investigates how people rank, rate, and assign relative proportions to their top 3 best and worst experiences

Why This Matters

Even if you are not a strict valence utilitarian, having the insight that the valence scale is long-tailed is still very important. Most ethical systems do give some weight to the prevention of suffering (in addition to the creation of subjectively valuable experiences), even if that is not all they care about. If your ethical system weighted slightly the task of preventing suffering when believing in a linear valence scale, then learning about the long-tailed nature of valence should in principle cause a major update. If indeed the worst experiences are exponentially more negative than originally believed by one’s ethical system, which nonetheless still cared about them, then after learning about the true valence scale the system would have to reprioritize. We suggest that while it might be unrealistic to have every ethical system refocus all of its energies on the prevention of intense suffering (and subsequently on researching how to create intense bliss sustainably), we can nonetheless expect such systems to raise this goal on their list of priorities. In other words, while “ending all suffering” will likely never be a part of most people’s ethical system, we hope that the data and arguments here presented at least persuade them to add “…and prevent intense forms of suffering” to the set of desiderata.

Indeed, lack of awareness about the long-tails of bliss and suffering may be the cause of an ongoing massive moral catastrophe (notes by Linch). If indeed the degree of suffering present in experiences follows a long-tail distribution, we would expect the worst experiences to dominate most utilitarian calculus. The biggest bang for the buck in altruistic interventions would therefore be those that are capable of directly addressing intense suffering and generating super-bliss.

General Ideas

The Non-Linearity of Pleasure and Pain

true_pleasure_scale

True long-tail pleasure scale (warning: psychedelics increase valence variance – the values here are for “good/lucky” trips and there is no guarantee e.g. LSD will feel good on a given occasion). Also: Mania is not always pleasant, but when it is, it can be super blissful.

true_pain_scale

True long-tail pain scale

As we’ve briefly discussed in previous articles (1, 2, 3), there are many reasons to believe that both pleasure and pain can be felt along a spectrum with values that range over possibly orders of magnitude. Understandably, someone who is currently in a state of consciousness around the human median of valence is likely to be skeptical of a claim like “the bliss you can achieve in meditation is literally 100 times better than eating your favorite food or having sex.” Intuitively, we only have so much space in our experience to fit bliss, and when one is in a “normal” or typical state of mind for a human, one is forced to imagine “ultra blissful states” by extrapolating the elements of one’s current experience, which certainly do not seem capable of being much better than, say, 50% of the current level of pleasure (or pain). The problem here is that the very building blocks of experiences that enable them to be ultra-high or ultra-low valence are themselves necessary to imagine accurately how they can be put together. Talking about extreme bliss to someone who is anhedonic is akin to talking about the rich range of possible color experiences to someone who is congenitally fully colorblind (cf. “What Mary Didn’t Know“).

“Ok”, you may say, “you are just telling me that pleasure and pain can be orders of magnitude stronger than I can even conceive of. What do you base this on?”. The most straightforward way to be convinced of this is to literally experience such states. Alas, this would be deeply unethical when it comes to the negative side, and it requires special materials and patience for the positive side. Instead, I will provide evidence from a variety of methods and conditions.

Personal Accounts

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I’ve been lucky to not have experienced major pain in my life so far (the worst being, perhaps, depression during my teens). I have, however, had two key experiences that gave me some time to introspect on the non-linear nature of pain. The first one comes from when I accidentally cut a super-spicy pepper and touched it with my bare hands (the batch of peppers I was cutting were mild, but a super-hot one snuck into the produce box). After a few minutes of cutting the peppers, I noticed that a burning heat began to intensify in my hands. This was the start of experiencing “hot pepper hands” for a full 8 hours (see other people’s experiences: 1, 2, 3). The first two to three hours of this ordeal were the worst, where I experienced what I rated as a persistent 4/10 pain interspersed with brief moments of 5/10 pain. The curious thing was that the 5/10 pain moments were clearly discernible as qualitatively different. It was as if the very numerous pinpricks and burning sensations all over my hands were in a somewhat disorganized state most of the time, but whenever they managed to build-up for long enough, they would start clicking with each other (presumably via phase-locking), giving rise to resonant waves of pain that felt both more energetic, and more aversive on the whole. In a way, this jump from what I rated as 4/10 to 5/10 was qualitative as well as quantitative, and it gave me some idea of how something that is already bad can become even worse.

My second experience involves a mild joint injury I experienced while playing Bubble Soccer (a very fun sport no doubt, and a common corporate treat for Silicon Valley cognotariats, but according to my doctor it is also a frequent source of injuries among programmers). Before doing physical therapy to treat this problem (which mostly took care of it), I remember spending hours introspecting on the quality of the pain in order to understand it better. It wasn’t particularly bad, but it was constant (I rated it as 2/10 most of the time). What stuck with me was how its constant presence would slowly increase the stress of my entire experience over time. I compared the experience to having an uncomfortable knot stuck in your body. If I had a lot of mental and emotional slack early in the day, I could easily take the stress produced by the knot and “send it elsewhere” in my body. But since the source of the stress was constant, eventually I would run out of space, and the knot would start making secondary knots around itself, and it was in those moments where I would rate the pain at a 3/10. This would only go away if I rested and somehow “reset” the amount of cognitive and emotional slack I had available.

The point of these two stories is to highlight the observation that there seem to be phase-changes between levels of discomfort. An analogy I often make is with the phenomenon of secondary coils when you twist a rope. The stress induced by pain- at least introspectively speaking- is pushed to less stressed areas of your mind. But this has a limit, which is until your whole world-simulation is stressed to the point that the source of stress starts creating secondary “stress coils” on top of the already stressed background experience. This was a very interesting realization to me, which put in a different light weird expressions that chronic pain patients use like “my pain now has a pain of its own” or “I can’t let the pain build up”.

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DNA coils and super-coils as a metaphor for pain phase-changes?

Consciousness Expansion

What about more extreme experiences? Here we should briefly mention psychedelic drugs, as they seem to be able to increase the energy of one’s consciousness (and in some sense “multiply the amount of consciousness“) in a way that grows non-linearly as a function of the dose. An LSD experience with 100 micrograms may be “only” 50% more intense than normal everyday life, but an LSD experience with 200 micrograms is felt as 2-3X as intense, while 300 micrograms may increase the intensity of experience by perhaps 10X (relative to normal). Usually people say that high-dose psychedelic states are indescribably more real and vivid than normal everyday life. And then there are compounds like 5-MeO-DMT, which people often describe as being in “a completely different category”, as it gives rise to what many describe as “infinite consciousness”. Obviously there is no such thing as an experience with infinite consciousness, and that judgement could be explained in terms of the lack of “internal boundaries” of the state, which gives the impression of infinity (not unlike how the surface of a torus can seem infinite from the point of view of a flatlander). That said, I’ve asked rational and intelligent people who have tried 5-MeO-DMT in non-spiritual settings what they think the intensity of their experiences was, and they usually say that a strong dose of 10mg or more gives rise to an intensity and “quantity” of consciousness that is at least 100X as high as normal everyday experiences. There are many reasons to be skeptical of this, no doubt, but the reports should not be dismissed out of hand.

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Secondary knots and links as a metaphor for higher bliss

As with the above example, we can reason that one of the ways in which both pain and pleasure can be present in *multiples* of one’s normal hedonic range is because the amount of consciousness crammed into a moment of experience is not a constant. In other words, when someone in a typical state of consciousness asks “if you say one can experience so much pain/pleasure, tell me, where would that fit in my experience? I don’t see much room for that to fit in here”, one can respond by saying that “in other states of consciousness there is more (phenomenal) time and space within each moment of experience”. Indeed, at Qualia Computing we have assembled and interpreted a large number of experiences of high-energy states of consciousness that indicate that both phenomenal time, and phenomenal space, can drastically expand. To sum it up – you can fit so much pleasure and pain in peak experiences precisely because such experiences make room for them.

Let us now illustrate the point with some paradigmatic cases of very high and vey low valence:

Peak Pleasure States: Jhanas and Temporal Lobe Seizures

On the pleasure side, we have Buddhist meditators who experience meditative states of absorption (aka. “Jhanas”) as extremely, and counter-intuitively, blissful:

The experience can include some very pleasant physical sensations such as goose bumps on the body and the hair standing up to more intense pleasures which grow in intensity and explode into a state of ecstasy. If you have pain in your legs, knees, or other part of the body during meditation, the pain will actually disappear while you are in the jhanas. The pleasant sensations can be so strong to eliminate your painful sensations. You enter the jhanas from the pleasant experiences exploding into a state of ecstasy where you no longer “feel” any of your senses.

9 Jhanas, Dhamma Wiki

There are 8 (or 9, depending on who you ask) “levels” of Jhanas, and the above is describing only the 1st of them! The higher the Jhana, the more refined the bliss becomes, and the more detached the state is from the common referents of our everyday human experience. Ultra-bliss does not look at all like sensual pleasure or excitement, but more like information-theoretically optimal configurations of resonant waves of consciousness with little to no intentional content (cf. semantically neutral energy). I know this sounds weird, but it’s what is reported.

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“Streamlines from the insula to the cortex” – the insula (in red) is an area of the brain intimately implicated in the super-bliss that sometimes precedes temporal lobe epilepsy (source)

Another example I will provide about ultra-bliss concerns temporal lobe epilepsy, which in a minority of sufferers gives rise to extraordinarily intense states of pleasure, or pain, or both. Such experiences can result in Geschwind syndrome, a condition characterized by hypergraphia (writing non-stop), hyper-religiosity, and a generally intensified mental and emotional life. No doubt, any experience that hits the valence scale at one of its extremes is usually interpreted as other-worldly and paranormal (which gives rise to the question of whether valence is a spiritual phenomenon or the other way around). Famously, Dostoevsky seems to have experienced temporal lobe seizures, and this ultimately informed his worldview and literary work in profound ways. Here is how he describes them:

“A happiness unthinkable in the normal state and unimaginable for anyone who hasn’t experienced it… I am then in perfect harmony with myself and the entire universe.”

 

– From a letter to his friend Nikolai Strakhov.

“I feel entirely in harmony with myself and the whole world, and this feeling is so strong and so delightful that for a few seconds of such bliss one would gladly give up 10 years of one’s life, if not one’s whole life. […] You all, healthy people, can’t imagine the happiness which we epileptics feel during the second before our fit… I don’t know if this felicity lasts for seconds, hours or months, but believe me, I would not exchange it for all the joys that life may bring.”

 

– from the character Prince Myshkin in Dostoevsky’s novel, The Idiot, which he likely used to give a voice to his own experiences.

Dostoevsky is far from the only person reporting these kinds of experiences from epilepsy:

As Picard [a scientist investigating seizures] cajoled her patients to speak up about their ecstatic seizures, she found that their sensations could be characterised using three broad categories of feelings (Epilepsy & Behaviour, vol 16, p 539). The first was heightened self-awareness. For example, a 53-year-old female teacher told Picard: “During the seizure it is as if I were very, very conscious, more aware, and the sensations, everything seems bigger, overwhelming me.” The second was a sense of physical well-being. A 37-year-old man described it as “a sensation of velvet, as if I were sheltered from anything negative”. The third was intense positive emotions, best articulated by a 64-year-old woman: “The immense joy that fills me is above physical sensations. It is a feeling of total presence, an absolute integration of myself, a feeling of unbelievable harmony of my whole body and myself with life, with the world, with the ‘All’,” she said.

 

– from “Fits of Rapture”, New Scientist (January 25, 2014) (source)

All in all, these examples illustrate the fact that blissful states can be deeper, richer, more intense, more conscious, and qualitatively superior to the normal everyday range of human emotion.

Now, how about the negative side?

Logarithmic Pain Scales: Stings, Peppers, and Cluster Headaches

“The difference between 6 and 10 on the pain scale is an exponential difference. Believe it or not.”

Insufferable Indifference, by Neil E. Clement (who experiences chronic pain ranging between 6/10 to 10/10, depending on the day)

Three pain-scale examples that illustrate the non-linearity of pain are: (1) the Schmidt sting pain index, (2) the Scoville scale, and (3) the KIP scale:

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(1) Justin O. Schmidt stung himself with over 80 species of insects of the Hymenoptera order, and rated the ensuing pain on a 4-point-scale. About the scale, he had to say the following:

4:28 – Justin Schmidt: The harvester ant is what got the sting pain scale going in the first place. I had been stung by honeybees, yellow jackets, paper wasps, etc. the garden variety stuff, that you get bitten by various beetles and things. I went down to Georgia, which has the Eastern-most extension of the harvester ant. I got stung and I said “Wooooow! This is DIFFERENT!” You know? I thought I knew everything there was about insect stings, I was just this dumb little kid. And I realized “Wait a minute! There is something different going on here”, and that’s what got me to do the comparative analysis. Is this unique to harvester ants? Or are there others that are like that. It turns out while the answer is, now we know much later – it’s unique! [unique type of pain]. 

[…]

7:09 – Justin Schmidt: I didn’t really want to go out and get stung for fun. I was this desperate graduate student trying to get a thesis, so I could get out and get a real job, and stop being a student eventually. And I realized that, oh, we can measure toxicity, you know, the killing power of something, but we can’t measure pain… ouch, that one hurts, and that one hurts, and ouch that one over there also hurts… but I can’t put that on a computer program and mathematically analyze what it means for the pain of the insect. So I said, aha! We need a pain scale. A computer can analyze one, two, three, and four, but it can’t analyze “ouch!”. So I decided that I had to make a pain scale, with the harvester ant (cutting to the chase) was a 3. Honey bees was a 2. And I kind of tell people that each number is like 10 equivalent of the number before. So 10 honey bee stings are equal to 1 harvester ant sting, and 10 harvester ant stings would equal one bullet ant sting.

[…]

11:50 – [Interviewer]: When I finally worked up the courage to [put the Tarantula Hawk on my arm] and take this sting. The sting of that insect was electric in nature. I’ve been shocked before, by accidentally taking a zap from an electrical cord. This was that times 10. And it put me on the ground. My arm seized up from muscle contraction. And it was probably the worst 5 minutes of my life at that point.

Justin Schmidt: Yeah, that’s exactly what I call electrifying. I say, imagine you are walking along in Arizona, and there is a wind storm, and the power line above snaps the wire, and it hits you, of course that hasn’t happened to me, but that’s what you imagine it feels like. Because it’s absolutely electrifying, I call it debilitating because you want to be macho, “ah I’m tough, I can do this!” Now you can’t! So I tell people lay down and SCREAM! Right?

[Interviewer]: That’s what I did! And Mark would be like, this famous “Coyote, are you ok? Are you ok?”

Justin Schmidt: No, I’m not ok!

[Interviewer]: And it was very hard to try to compose myself to be like, alright, describe what is happening to your body right now. Because your mind goes into this state that is like blank emptiness. And all you can focus on is the fact that there’s radiating pain coming out of your arm.

Justin Schmidt: That’s why you scream, because now you’re focusing on something else. In addition to the pain, you’re focusing on “AAAAAAHHHHH!!!” [screams loudly]. Takes a little bit of the juice off of the pain, so maybe you lower it down to a three for as long as you can yell. And I can yell for a pretty long time when I’m stung by a tarantula hawk.

 

Origin of STINGS!, interview of Justin O. Schmidt

If we take Justin’s word for it, a sting that scores a 4 on his pain scale is about 1,000 times more painful than a sting that scores a 1 on his scale. Accordingly, Christopher Starr (who replicated the scale), stated that any sting that scores a 4 is “traumatically painful” (source). Finally, since the scale is restricted to stings of insects of the Hymenoptera order, it remains possible that there are stings whose pain would be rated even higher than 4. A 5 on the sting pain index might perhaps be experienced with the stings of the box jellyfish that produces Irukandji syndrome, and the bite of the giant desert centipede. Needless to say, these are to be avoided.

Moving on…

(2) The Scoville scale measures how spicy different chili peppers and hot sauces are. It is calculated by diluting the pepper/sauce in water until it is no longer possible to detect any spice in it. The number that is associated with the pepper or sauce is the ratio of water-to-sauce that makes it just barely possible to taste the spice. Now, this is of course not itself a pain scale. I would nonetheless anticipate that taking the log of the Scoville units of a dish might be a good approximation for the reported pain it delivers. In particular, people note that there are several qualitative jumps in the type and nature of the pain one experiences when eating hot sauces of different strengths (e.g. “Fuck you Sean! […] That was a leap, Sean, that was a LEAP!” – Ken Jeong right after getting to the 135,000 Scoville units sauce in the pain porn Youtube series Hot Ones). Amazon reviews of ultra-hot sauces can be mined for phenomenological information concerning intense pain, and the general impression one gets after reading such reviews is that indeed there is a sort of exponential range of possible pain values:

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I know it may be fun to trivialize this kind of pain, but different people react differently to it (probably following a long-tail too!). For some people who are very sensitive to heat pain, very hot sauce can be legitimately traumatizing. Hence I advise against having ultra-spicy sauces around your house. The novelty value is not worth the probability of a regrettable accident, as exemplified in some of the Amazon reviews above (e.g. a house guest assuming that your “Da’Bomb – Beyond Insanity” bottle in the fridge can’t possibly be that hot… and ending up in the ER and with PTSD).

I should add that media that is widely consumed about extreme hot sauce (e.g. the Hot Ones mentioned above and numerous stunt Youtube channels) may seem fun on the surface, but what doesn’t make the cut and is left in the editing room is probably not very palatable at all. From an interview: “Has anyone thrown up doing it?” (interviewer) – “Yeah, we’ve run the gamuts. We’ve had people spit in buckets, half-pass out, sleep in the green room afterwards, etc.” (Sean Evans, Hot Ones host). T.J. Miller, when asked about what advice he would give to the show while eating ultra-spicy wings, responded: “Don’t do this. Don’t do this again. End the show. Stop doing the show. That’s my advice. This is very hot. This is painful. There’s a problem here.”

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Trigeminal Neuralgia pain scale – a condition similarly painful to Cluster Headaches

(3) Finally, we come to the “KIP scale”, which is used to rate Cluster Headaches, one of the most painful conditions that people endure:

The KIP scale

KIP-0 No pain, life is beautiful
KIP-1 Very minor, shadows come and go. Life is still beautiful
KIP-2 More persistent shadows
KIP-3 Shadows are getting constant but can deal with it
KIP-4 Starting to get bad, want to be left alone
KIP-5 Still not a “pacer” but need space
KIP-6 Wake up grumbling, curse a bit, but can get back to sleep without “dancing”
KIP-7 Wake up, sleep not an option, take the beast for a walk and finally fall into bed exhausted
KIP-8 Time to scream, yell, curse, head bang, rock, whatever works
KIP-9 The “Why me?” syndrome starts to set in
KIP-10 Major pain, screaming, head banging, ER trip. Depressed. Suicidal.

The duration factor is multiplied by the intensity factor, which uses the KIP scale in an exponential way – a KIP 10 is not just twice as bad as a KIP 5, it’s ten times as intense.

Source: Keeping Track, by Cluster Busters

As seen above, the KIP scale is acknowledged by its creator and users to be logarithmic in nature.

In summary: We see that pleasure comes in various grades and that peak experiences such as those induced by psychedelics, meditation, and temporal lobe seizures seem to be orders of magnitude more energetic and better than everyday sober states. Likewise, we see that across several categories of pain, people report being surprised by the leaps in both quality and intensity that are possible. More so, at least in the case of the Schmidt Index and the Kip Scale, the creators of the scale were explicit that it was a logarithmic mapping of the actual level of sensation.

While we do not have enough evidence (and conceptual clarity) to assert that the intensity of pain and pleasure does grow exponentially, the information presented so far does suggest that the valence of experiences follows a long-tail distribution.

Deference-type Approaches for Experience Ranking

The above considerations underscore the importance of coming up with a pleasure-pain scale that tries to take into account the non-linearity and non-normality of valence ratings. One idea we came up with was a “deference”-type approach, where we ask open-ended questions about people’s best and worst experiences and have them rank them against each other. Although locally the data would be very sparse, the idea was that there might be methods to integrate the collective patterns of deference into an approximate scale. If extended to populations of people who are known to have experienced extremes of valence, the approach would even allow us to unify the various pain scales (Scoville, Schmidt, KIP, etc.) and assign a kind of universal valence score to different categories of pain and pleasure.* That will be version 2.0. In the meantime, we thought to try to get a rough picture of the extreme joys and affections of members of the general public, which is what this article will focus on.

Normal World vs. Lognormal World

There is a world we could call the “Normal World”, where valence outliers are rare and most types of experiences affect people more or less similarly, distributed along a Gaussian curve. Then there is another, very different world we could call the “long-tailed world” or if we want to make it simple (acknowledging uncertainty) “Lognormal World”, where almost every valence distribution is a long-tail. So in the “Lognormal World”, say, for pleasure (and symmetrically for pain), we would expect to see a long-tail in the mean pleasure of experiences between different categories across all people, a long-tail in the amount of pleasure within a given type of experience across people, a long-tail for the number of times an individual has had a certain type of pleasure, a long-tail in the intensity of the pleasure experienced with a single category of experience within a single person, and so on. Do we live in the Normal World or the Lognormal World?

Predictions of Lognormal World

If we lived in the “Lognormal World”, we would expect:

  • That people will typically say that their top #1 best/worst experience is not only a bit better/worse than their #2 experience, but a lot better/worse. Like, perhaps, even multiple times better/worse.
  • That there will be a long-tail in the number of appearances of different categories (i.e. that a large amount, such as 80%, of top experiences will belong to the same narrow set of categories, and that there will be many different kinds of experiences capturing the remaining 20%).
  • That for most pairs of experiences x and y, people who have had both instances of x and y, will usually agree about which one is better/worse. We call such a relationship a “deference”. More so, we would expect to see that deference, in general, will be transitive (a > b and b > c implying that a > c).

To test the first and second prediction does not require a lot of data, but the third does because one needs to have enough comparisons to fill a lot of triads. The survey results we will discuss bellow are congruent with the first and second prediction. We did what we could with the data available to investigate the third, and tentatively, it seems to hold up (with ideas like deference network centrality analysis, triadic analysis, and tournament-style approaches).


Survey Setup

The survey asked the following questions: current level of pleasure, current level of pain, top 3 most pleasurable experiences (in decreasing order) along with pleasure ratings for each of them and the age when they were experienced, and the same for the top 3 most painful experiences. I specifically did not provide a set of broad categories (such as “physical” or “emotional”) or a drop-down menu of possible narrow categories (e.g. going to the movies, aerobic exercise, etc.). I wanted to see what people would say when the question was as open-ended as possible.

I also included questions aimed more directly at probing the long-tailed nature of valence: I asked participants to rate “how many times more pleasant was the #1 top experience relative to the #2 top experience” (and #2 relative to #3, and the same for the top most painful experiences).

I also asked them to describe in more detail the single most pleasant and unpleasant experiences, and added a box for comments at the end in order to see if anyone complained about the task (most people said “no comment”, many said they enjoyed the task, and one person said that it made them nostalgic). I also asked about basic demographics (age and gender). Participants earned $1.75 for the task, which seems reasonable given the time it took to complete in most cases.

Mechanical Turk: Participant Composition

The survey was run on Mechanical Turk. I requested “Masters” qualifications for 90/110 of the survey responses. To be a Mechanical Turk Master you need to have a good track record of task approval, which I reasoned would increase the rate of well thought-out high-quality responses (this turned out to be true). The participants’ genders were fairly balanced (50/97 women, 47/97 men), and the average age was 36.5 years (sd = 10):

age_distribution_no_bots

Age distribution

Bots (easy to spot – unless extremely sophisticated)

While reading the responses I discovered that some of them seemed to be generated by bots. Apparently task requesters started noticing the presence of bots a couple of years ago. This is obviously a problem for academics trying to use the service for their research, and for machine learning professionals using the service for data-tagging. Having been both of those things in the past, I can say that a few years ago I did not see any submissions that looked suspiciously bot-like. Though low-quality rushed responses did seem to be relatively common back then, I never observed bot-like responses to open-ended questions. Unfortunately this time I was able to spot several responses clearly written by bots. For example, one respondent answered the question “write a brief essay about your #1 best experience” with:

The reason these types of assignments are given so often is that anyone can write about their own experience and it doesn’t require any outside resources or research. However, even though anyone can tell a story about their life, that does not mean anyone can write a good essay about that experience. As a professor and teacher for 30 years, I’ve read thousands of essays and can tell you there is a distinct difference from telling a story about yourself and writing an excellent personal experience essay. The difference between good and great:

And it ends that way, with a colon indicating that the respondent is about to explain what the difference between good and great is. But it never does it. This answer, great, it is not.

In most cases the difference between a genuine response and a bot response was very obvious. That said, I erred on the side of caution for filtering bots and I got rid of answers even if they seemed just a little suspicious. This left me with 97 out of the 110 original responses. The following analysis was conducted on those 97 responses.

Preprocessing

Since the responses were open-ended I had to tag each of them with an experience category. To do this I read each response and identified the key theme in them and classified them with a label that was specific enough to distinguish it from nearby experiences (e.g. different types of fractures), but not so specific that we would never get more than one response per category (e.g. “breaking the middle finger in elementary school”). In general, most responses fell into very unambiguous categories (e.g. “When my father passed away” and “Watching my father die and take his last few breaths.” were both classified as “Father death”). About 10% of the responses were relatively ambiguous: it wasn’t clear what the source of the pain or pleasure was. To deal with those responses I used the label “Unspecified”. When some detail was present but ambiguity remained, such as when a broad type of pain or pleasure was mentioned but not the specific source I tagged it as “Unspecified X” where X was a broad category. For example, one person said that “broken bones” was the most painful experience they’ve had, which I labeled as “Unspecified fracture”.


Results

I should preface the following by saying that we are very aware of the lack of scientific rigor in this survey; it remains a pilot exploratory work. We didn’t specify the time-scale for the experiences (e.g. are we asking about the best minute of your life or the best month of your life?) or whether we were requesting instances of physical or psychological pain/pleasures. Despite this lack of constraints it was interesting to see very strong commonalities among people’s responses:

Appearance Base Rates

There were 77 and 124 categories of pleasure and pain identified, respectively. On the whole it seemed like there was a higher diversity of ways to suffer than of ways to experience intense bliss. Summoning the spirit of Tolstoy: “Happy families are all alike; every unhappy family is unhappy in its own way.”

Here are the raw counts for each category with at least two appearances:

pleasure_baserates_97_only_2andup_

Best experiences appearances (with at least two reports)

pain_baserates_97_only_2andup_

Worst experience appearances (with at least two reports)

For those who want to see the full list of number of appearances for each experience mentioned see the bottom of the article (I also clarify some of the more confusing labels there too)**.

A simple way to try to incorporate the information about the ranking is to weight experiences rated as top #1 with 3 points, those as top #2 with 2 points, and those as the top #3 with 1 point. If you do this, the experiences scores are:

pleasure_baserates_97_weighted_

Weighted appearances of best experiences (#1 – 3 points, #2 – 2 points, #3 – 1 point)

pain_baserates_97_weighted_

Weighted appearances of worst experiences (#1 – 3 points, #2 – 2 points, #3 – 1 point)

Average ratings

Given the relatively small sample size, I will only report the mean rating for pain and pleasure (out of 10) for categories of experience for which there were 6 or more respondents:

For pain:

  1. Father death (n = 19): mean 8.53, sd 2.3
  2. Childbirth (n = 16): mean 7.94, sd 2.16
  3. Grandmother death (n = 13): mean 8.12, sd 2.5
  4. Mother death (n = 11): mean 9.4, sd 0.62
  5. Car accident (n = 9): mean 8.42, sd 1.52
  6. Kidney stone (n = 9): mean 5.97, sd 3.17
  7. Migraine (n = 9): mean 5.36, sd 3.11
  8. Romantic breakup (n = 9): mean 7.11, sd 1.52
  9. Broken arm (n = 6): mean 8.28, sd 0.88
  10. Broken leg (n = 6): mean 7.33, sd 2.02
  11. Work failure (n = 6): mean 5.88, sd 3.57

(Note: the very high variance for kidney stones and migraine is partly explained by the presence of some very low responses, with values as low as 1.1/10 – perhaps misreported, or perhaps illustrating the extreme diversity of experiences of migraines and kidney stones).

And for pleasure:

  1. Falling in love (n = 42): mean 8.68, sd 1.74
  2. Children born (n = 41): mean 9.19, sd 1.64
  3. Marriage (n = 21): mean 8.7, sd 1.25
  4. Sex (n = 19): mean 8.72, sd 1.45
  5. College graduation (n = 13): mean 7.73, sd 1.4
  6. Orgasm (n = 11): mean 8.24, sd 1.63
  7. Alcohol (n = 8): mean 6.84, sd 1.59
  8. Vacation (n = 6): mean 9.12, sd 0.73
  9. Getting job (n = 6): mean 7.22, sd 1.47
  10. Personal favorite sports win (n = 6): mean 8.17, sd 1.23

Deference Graph of Top Experiences

We will now finally get to the more exploratory and fun/interesting analysis, at least in that it will generate a cool way of visualizing what causes people great joy and pain. Namely, the idea of using people’s rankings in order to populate a global scale across people and show it in the form of a graph of deferences. While the scientific literature has some studies that compare pain across different categories (e.g. 1, 2, 3) I was not able to find any dataset that included actual rankings across a variety of categories. Hence why it was so appealing to visualize this.

The simplest way of graphing experience deferences is to assign a node to each experience category and add an edge between experiences with deference relationships with a weight proportional to the number of directed deferences. For example, if 4 people have said that A was better than B, and 3 people have said that B was better than A, then there will be an edge from A to B with a weight of 4 and an edge from B to A with a weight of 3. Additionally, we can then run a graph centrality algorithm such as PageRank to see where the “deferences end up pooling”.

The images below do this: the PageRank of the graph is represented with the color gradient (darker shades of green/red representing higher PageRank values for good/bad experiences). In addition, the graphs also represent the number of appearances in the dataset for each category with the size of each node:

The main problem with the approach above is that it double (triple?) counts experiences that are very common. Say that, for example, taking 5-MeO-DMT produces a consistently higher-valence feeling relative to having sex. If we only have a couple of people who report both 5-MeO-DMT and sex as their top experiences, the edge from sex to 5-MeO-DMT will be very weak, and the PageRank algorithm will underestimate the value of 5-MeO-DMT.

In order to avoid the double counting effect of commonly-reported peak experiences we can instead add edge weights on the basis of the proportion with which an experience defers to the other. Let’s say that f(a, b) means “number of times that b is reported as higher than a”. Then the proportion would be f(a, b) / (f(a, b) + f(b, a)). Now, this introduces another problem, which is that pairs of experiences that appear together very infrequently might get a very high proportion score due to a low sample size. In order to prevent this we use Laplace smoothing and modify the equation to (f(a, b) + 1) / (f(a, b) + f(b, a) + 2). Finally, we transform this proportion score from the range of 0 to 1 to the range of -1 to 1 by multiplying by 2 and subtracting one. We call this a “rebalanced smoothed proportion” w(a, b):

CodeCogsEqn

Rebalanced smoothed proportion

I should note that this is not based on any rigorous math. The equation is based on my intuition for what I would expect to see in such a graph, namely a sort of confidence-weighted strength of directionality, but I do not guarantee that this is a principled way of doing so (did I mention this is a pilot small-scale low-budget ‘to a first approximation’ study?). I think that, nonetheless, doing this is still an improvement upon merely using the raw deference counts as the edge weights. To visualize what w(a, b) looks like I graphed its values for a and b in the range of 0 to 20 (literally typing the equation into the google search bar):

To populate the graph I only use the positive edge weights so that we can run the PageRank algorithm on it. This now looks a lot more reasonable and informative as a deference graph than the previous attempts:

pleasure_97_balanced_2

Best experiences deference graph: Edge weights based on the rebalanced smoothed proportions, size of nodes is proportional to number of appearances in the dataset, and the color tracks the PageRank of the graph. Edge color based on source node.

 

pain_network_97_balanced

Worst experiences deference graph: Edge weights based on the rebalanced smoothed proportions, size of nodes is proportional to number of appearances in the dataset, and the color tracks the PageRank of the graph. Edge color based on source node.

By taking the PageRank of these graphs (calculated with NetworkX) we arrive at the following global rankings:

pleasure_pagerank_97_

PageRank of the graph of best experiences with edge weights computed with the rebalanced smoothed proportion equation

pain_pagerank_97__

PageRank of the graph of worst experiences with edge weights computed with the rebalanced smoothed proportion equation

Intuitively this ranking seems more aligned with what I’ve heard before, but I will withhold judgement on it until we have much more data.

Triadic Analysis

With a more populated deference graph we can analyze in detail the degree to which triads (i.e. sets of three experiences such that each of the three possible deferences are present in the graph) show transitivity (cf. Balance vs. Status Theory).

In particular, we should compare the prevalence of these two triads:

triad_analysis

Left: 030T, Right: 030C (source)

The triads above are 030T, which is transitive, and 030C, which is a loop. The higher the degree of agreement between people and the higher the probability of the existence of an underlying shared scale, we would expect to see more triads of the type 030T relative to 030C. That said, a simple ratio is not enough, since the expected proportion between these two triads can be an artifact of the way the graph is constructed and/or its general shape (and hence the importance of comparing against randomized graphs that preserve as many other statistical features as possible). With our graph, we noticed that the very way in which the edges were introduced generated an artifact of a very strong difference between these two types of triads:

In the case of pain there are 105 ‘030T’, and 3 ‘030C’. And for the pleasure questions there were 98 ‘030T’, and 9 ‘030C’. That said, many of these triads are the artifact of taking into account the top three experiences, which already generates a transitive triad by default when n = 1 for that particular triad of experiences. To avoid this artifact, we filtered the graph by only adding edges when a pair of experiences appeared at least twice (and discounting the edges where w(a, b) = 0). With this adjustment we got 2 ‘030T’, and 1 ‘030C’ for the pain questions, and 1 ‘030T’, and 0 ‘030C’ for the pleasure question. Clearly there is not enough data to meaningfully conduct this type of analysis. If we extend the study and get a larger sample size, this analysis might be much more informative.

Latent Trait Ratings

A final approach I tried for deriving a global ranking of experiences was to assume a latent parameter for pain or pleasure of different experiences and treating the rankings as the tournament results of participants with skill equal to this latent trait. So when someone says that an experience of sex was better than an experience of getting a new bike we imagine that “sex” had a match with “getting bike” and that “sex” won that match. If we do this, then we can import any of the many tournament algorithms that exist (such as the Elo rating system) in order to approximate the latent “skill” trait of each experience (except that here it is the “skill” to cause you pleasure or pain, rather than any kind of gaming ability).

Interestingly, this strategy has also been used in other areas outside of actual tournaments, such as deriving university rankings based on the choices made by students admitted to more than one college (see: Revealed Preference Rankings of US Colleges and Universities).

I should mention that the fact that we are asking about peak experiences likely violates some of the assumptions of these algorithms, since the fact that a match takes place is already information that both experiences made it into the top 3. That said, if the patterns of deference are very strong, this might not represent a problem.

To come up with this tournament-style ranking I decided to go for a state-of-the-art algorithm. The one that I was able to find and use was Microsoft Research’s algorithm called TrueSkill (which is employed to rank players in Xbox LIVE). According to their documentation, to arrive at a conservative “leaderboard” that balances the estimated “true skill” and the uncertainty around it, they recommend ranking by the expected skill level minus three times the standard error around this estimate. If we do this, we arrive at the following experience “leaderboards”:

pleasure_97_trueskill_conservative

Conservative TrueSkill scores for best experiences (mu – 3*sigma)

pain_97_trueskill_conservative

Conservative TrueSkill scores for worst experiences (mu – 3*sigma)

Long-tails in Responses to “How Many Times Better/Worse” Question

The survey included four questions aimed at comparing the relative hedonic values of peak experiences: “Relative to the 1st most pleasant experience, how many times better was the 2nd most pleasant experience?” (This was one, the other three were the permutations of also asking about 2nd vs. 3rd and about the bad experiences):

(Note: I’ll ignore the responses to the comparison between the 2nd and 3rd worst pains because I messed up the question -I forgot to substitute “better” for “worse”).

I would understand the skepticism about these graphs. But at the same time, I don’t think it is absurd that for many people the worst experience they’ve had is indeed 10 or 100 times worse than the second worst. For example, someone who has endured a bad Cluster Headache will generally say that the pain of it is tens or hundreds of times worse than any other kind of pain they have had (say, breaking a bone or having skin burns).

The above distributions suggest a long-tail for the hedonic quality of experiences: say that the hedonic quality of each day is distributed along a log-normal distribution. A 45 year old has experienced roughly 17,000 days. Let’s say that such a person’s experience of pain each day is sampled from a log-normal distribution with a Gaussian exponent with a mean of 10 and a standard deviation of 5. If we take 100 such people, and for each of them we take the single worst and the second worst days of their lives, and then take the ratio between them, we will have a distribution like this (simulated in R):

If you smooth the empirical curves above you would get a distribution that looks like these simulations. You really need a long-tail to be able to get results like “for 25% of the participants the single worst experience was at least 4 times as bad as the 2nd worst experience.” Compare that to the sort of pattern that you get if the distribution was normal rather than log-normal:

As you can see (zooming in on the y-axis), the ratios simply do not reach very high values. With the normal distribution simulated here, we see that the highest ratio we achieve is around 1.3, as opposed to the empirical ratios of 10+.*** If you are inclined to believe the survey responses- or at least assign some level of credibility to the responses in the 90th-percentile and below-, the data is much more consistent with a long-tail distribution for hedonic values relative to a normal distribution.

Discussion

Key Pleasures Surfaced

Birth of children

I have heard a number of mothers and father say that having kids was the best thing that ever happened to them. The survey showed this was a very strong pattern, especially among women. In particular, a lot of the reports deal with the very moment in which they held their first baby in their arms for the first time. Some quotes to illustrate this pattern:

The best experience of my life was when my first child was born. I was unsure how I would feel or what to expect, but the moment I first heard her cry I fell in love with her instantly. I felt like suddenly there was another person in this world that I cared about and loved more than myself. I felt a sudden urge to protect her from all the bad in the world. When I first saw her face it was the most beautiful thing I had ever seen. It is almost an indescribable feeling. I felt like I understood the purpose and meaning of life at that moment. I didn’t know it was possible to feel the way I felt when I saw her. I was the happiest I have ever been in my entire life. That moment is something that I will cherish forever. The only other time I have ever felt that way was with the subsequent births of my other two children. It was almost a euphoric feeling. It was an intense calm and contentment.

—————

I was young and had a difficult pregnancy with my first born. I was scared because they had to do an emergency c-section because her health and mine were at risk. I had anticipated and thought about how the moment would be when I finally got to hold my first child and realize that I was a mother. It was unbelievably emotional and I don’t think anything in the world could top the amount of pleasure and joy I had when I got to see and hold her for the first time.

—————

I was 29 when my son was born. It was amazing. I never thought I would be a father. Watching him come into the world was easily the best day of my life. I did not realize that I could love someone or something so much. It was at about 3am in the morning so I was really tired. But it was wonderful nonetheless.

—————

I absolutely loved when my child was born. It was a wave of emotions that I haven’t felt by anything before. It was exciting and scary and beautiful all in one.

No luck for anti-natalists… the super-strong drug-like effects of having children will presumably continue to motivate most humans to reproduce no matter how strong the ethical case against doing so may be. Coming soon: a drug that makes you feel like “you just had 10,000 children”.

Falling in Love

The category of “falling in love” was also a very common top experience. I should note that the experiences reported were not merely those of “having a crush”, but rather, they typically involved unusually fortunate circumstances. For instance, a woman reported being friends with her crush for 7 years. She thought that he was not interested in her, and so she never dared to confess her love for him… until one day, out of the blue, he confessed his love for her. Other experiences of falling in involve chance encounters with childhood friends that led to movie-deserving romantic escapades, forbidden love situations, and cases where the person was convinced the lover was out of his or her league.

Travel/Vacation

The terms “travel” and “vacation” may sound relatively frivolous in light of some of the other pleasures listed. That said, these were not just any kind of travel or vacation. The experiences described do seem rather extraordinary and life-changing. For example, talking about back-packing alone in France for a month, biking across the US with your best friend, or a long trip in South East Asia with your sibling that goes much better than planned.

MDMA/LSD/Psilocybin

It is significant that out of 97 people four of them listed MDMA as one of the most pleasant experiences of their lives. This is salient given the relatively low base rate of usage of this drug (some surveys saying about 12%, which is probably not too far off from the base rate for Mechanical Turk workers using MDMA). This means that a high percentage of people who have tried MDMA will rate it as as one of their top experiences, thus implying that this drug produces experiences sampled from an absurdly long-tailed high-valence distribution. This underscores the civilizational significance of inventing a method to experience MDMA-like states of consciousness in a sustainable fashion (cf. Cooling It Down To Partying It Up).

Likewise, the appearance of LSD and psilocybin is significant for the same reason. That said, measures of the significance of psychedelic experiences in psychedelic studies have shown that a high percentage of those who experience such states rate them among their top most meaningful experiences.

About-two-thirds-of-participants-who-received-psilocybin-reported-a-mystical-experience

Games of Chance Earnings

Four participants mentioned earnings in games of chance. These cases involved earning amounts ranging from $2,000 all the way to a truck (which was immediately sold for money). What I find significant about this is that these experiences are at times ranked above “college graduation” and other classically meaningful life moments. This brings about a crazy utilitarian idea: if indeed education is as useless as many people in the intellectual elite are saying these days (ex. The Case Against Education) we might as well stop subsidizing higher education and instead make people participate in opt-out games of chance rigged in their favor. Substitute the Department of Education for a Department of Lucky Moments and give people meaningful life experiences at a fraction of the cost.

Key Pains Surfaced

Kidney Stones and Migraines

The fact that these two medical issues were surfaced is, I think, extremely significant. This is because the lifetime incidence of kidney stones is about 10% (~13% for men, 7% for women) and for migraines it is around 13% (9% for men, 18% for women). In the survey we saw 9/93 people mentioning kidney stones, and the same number of people mentioning migraines. In other words, there is reason to believe that a large fraction of the people who have had either of these conditions will rate them as one of their top 3 most painful experiences. This fact alone underscores the massive utilitarian benefit that would come from being able to reduce the incidence of these two medical problems (luckily, we have some good research leads for addressing these problems at a large scale and in a cost-effective way: DMT for migraines, and frequency specific microcurrent for kidney stones)

Childbirth

Childbirth was mentioned 16 times, meaning that roughly 30% of women rate it as one of their three most painful experiences. While many people may look at this and simply nod their heads while saying “well, that’s just life”, here at Qualia Computing we do not condone that kind of defeatism and despicable lack of compassion. As it turns out, there are fascinating research leads to address the pain of childbirth. In particular, Jo Cameron, a 70 year old vegan schoolteacher, described her childbirth by saying that it “felt like a tickle”. She happens to have a mutation in the FAAH gene, which is usually in charge of breaking down anandamine (a neurotransmitter implicated in pain sensitivity and hedonic tone). As we’ve argued before, every child is a complete genetic experiment. In the future, we may as well try to at least make educated guesses about our children’s genes associated with low mood, anxiety, and pain sensitivity. In defiance of common sense (and the Bible) the future of childbirth could indeed be one devoid of intense pain.

Car accidents

Car accidents are extremely common (the base rate is so high that by the age of 40 or so we can almost assume that most people have been in at least one car accident, possibly multiple). More so, it seems likely that the health-damaging effects of car accidents, by their nature, follow a long-tail distribution. The high base rate of people mentioning car accidents in their top 3 most painful experiences underscores the importance of streamlining the process of transitioning into the era of self-driving cars.

Death of Father and Mother

This one does not come as a surprise, but what may stand out is the relatively higher frequency of mentions of “death of father” relative to “death of mother”. I think this is an artifact of the longevity difference between men and women. This is in agreement with the observed effect of age: about 15% vs. 25% of people under and over 40 had mentioned the death of their father, as opposed to a difference of 5% vs. 25% for death of mother. The reason why the father might be over-represented might simply be due to the lower life expectancy of men relative to women, and hence the father, on average, dying earlier. Thus, it being reported more frequently by a younger population.

Future Directions for Methodological Approaches:

Graphical Models with Log-normal Priors

After trying so many analytic angles on this dataset, what else is there to do? I think that as a proof of concept the analysis presented here is pretty well-rounded. If the Qualia Research Institute does well in the funding department, we can expect to extend this pilot study into a more comprehensive analysis of the pleasure-pain axis both in the general population and among populations who we know have endured or enjoyed extremes of valence (such as cluster headache sufferers or people who have tried 5-MeO-DMT).

In terms of statistical models, an adequate amount of data would enable us to start using probabilistic graphical models to determine the most likely long-tail distributions for all of the key parameters of pleasure and pain. For instance, we might want to develop a model similar to Item Response Theory where:

  1. Each participant samples experiences from a distribution.
  2. Each experience category generates samples with an empirically-determined base rate probability (e.g. chances that it happens in a given year), along with a latent hedonic value distribution.
  3. A “discrimination function” f(a, b) that gives the probability that experience of hedonic value a is rated as more pleasant (or painful) relative an experience with a hedonic value of b.
  4. And a generative model that estimates the likelihood of observing experiences as the top 3 (or top x) based on the parameters provided.

In brief, with an approach like the above we can potentially test the model fit for different distribution types of hedonic values per experience. In particular, we would be able to determine if the model fit is better if the experiences are drawn from a Gaussian vs. a log-normal (or other long-tailed) distribution.

Finally, it might be fruitful to explicitly ask about whether participants have had certain experiences in order to calibrate their ratings, or even have them try a battery of standardized pain/pleasure-inducing stimuli (capsaicin extract, electroshocks, stings, massage, orgasm, etc.). We could also find the way to combine (a) the numerical ratings, (2) the ranking information, and (3) the “how many times better/worse” responses into a single model. And for best results, restrict the analysis to very recent experiences in order to reduce recall biases.

Closing Thoughts on the Valence Scale

To summarize, I believe that the case for a long-tail account of the pleasure-pain axis is very defensible. This picture is supported by:

  1. The long-tailed nature of neuronal cascades,
  2. The phenomenological accounts of intense pleasure and pain (w/ phenomenological accounts of time and space expansion),
  3. The way in which pain scales are constructed by those who developed them, and
  4. The analytic results of the pilot study we conducted and presented here.

In turn, these results give rise to a new interpretation of psychophysical observations such as Weber’s Law. Namely, that Just Noticeable Differences may correspond to geometric differences in qualia, not only in sensory stimuli. That is, that the exponential nature of many cases where Weber’s Law appears are not merely the result of a logarithmic compression on the patterns of stimulation at the “surface” of our sense organs. Rather, the observations presented here suggest that these long-tails deal directly with the quality and intensity of conscious experience itself.


Additional Material

Dimensionality of Pleasure and Pain

Pain and pleasure may have an intrinsic “dimensionality”. Without elaborating, we will merely state that a generative definition for the “dimensionality of an experience” is the highest “virtual dimension” implied by the patterns of correlation between degrees of freedom. The hot pepper hands account I related suggested a kind of dimensional phase transition between 4/10 and 5/10 pain, where the patterns of a certain type (4/10 “sparks” of pain) would sometimes synchronize and generate a new type of higher-dimensional sensation (5/10 “solitons” of pain). To illustrate this idea further:

First, in Hot Ones, Kumail Nanjiani describes several “leaps” in the spiciness of the wings, first at around 30,000 Scoville (“this new ghost that appears and only here starts to visit you”), and second at around 130k Scoville (paraphrasing: “like how NES to Super Nintendo felt like a big jump, but then Super Nintendo to N64 was an even bigger leap” – “Now we are playing in the big leagues motherfucker! This is fucking real!”). This hints at a change in dimensionality, too.

And second, Shinzen Young‘s advice about dealing with pain involves not resisting it. He discusses how suffering is generated by the coordination between emotional, cognitive, and physical mental formations. If you can keep each of these mental formations happening independently and don’t allow their coordinated forms, you will avoid some of what makes the experience bad. This also suggests that higher-dimensional pain is qualitatively worse. Pragmatically, training to do this may make sense for the time being, since we are still some years away from sustainable pain-relief for everyone.

Mixed States

We have yet to discuss in detail how mixed states come into play for a log-normal valence scale. The Symmetry Theory of Valence would suggest that most states are neutral in nature and that only processes that reduce entropy locally such as neural annealing would produce highly-valenced states. In particular, we would see that high-valence states have very negative valence states nearby in configuration space; if you take a very good high-energy state and distort it in a random direction it will likely feel very unpleasant. The points in between would be mixed valence, which account for the majority of experiences in the wild.

Qualia Formalism

Qualia Formalism posits that for any given system that sustains experiences, there is a mathematical object such that the mathematical features of that object are isomorphic to the system’s phenomenology. In turn, Valence Structuralism posits that the hedonic nature of experience is encoded in a mathematical feature of this object. It is easier to find something real if you posit that it exists (rather than try to explain it away). We have suggested in the past that valence can be explained in terms of the mathematical property of symmetry, which cashes out in the form of neural dissonance and consonance.

In contrast to eliminativist, illusionist, and non-formal approaches to consciousness, at QRI we simply start by assuming that experience has a deep ground truth structure and we see where we can go from there. Although we currently lack the conceptual schemes, science, and vocabulary needed to talk in precise terms about different degrees of pleasure and pain (though we are trying!), that is not a good reason to dismiss the first-person claims and indirect pieces of evidence concerning the true amounts of various kinds of qualia bound in each moment of experience. If valence does turn out to intrinsically be a mathematical feature of our experience, then both its quality and quantity could very well be precisely measurable, conceptually crisp, and tractable. A scientific fact that, if proven, would certainly have important implications in ethics and meta-ethics.


Notes:

* It’s a shame that Coyote Peterson didn’t rate the pain produced by the various wings he ate on the Hot Ones show relative to insect stings, but that sort of data would be very helpful in establishing a universal valence scale. More generally, stunt-man personalities like the L.A. Beast who subject themselves to extremes of negative valence for Internet points might be an untapped gold mine for experience deference data (e.g. How does eating the most bitter substance known compare with the bullet ant glove? Asking this guy might be the only way to find out, without creating more casualties).

**Base rate of mentions of worst experiences:

[('Father death', 19), ('Childbirth', 16), ('Grandmother death', 13), ('Mother death', 11), ('Car accident', 9), ('Kidney stone', 9), ('Migraine', 9), ('Romantic breakup', 9), ('Broken arm', 6), ('Broken leg', 6), ('Work failure', 6), ('Divorce', 5), ('Pet death', 5), ('Broken foot', 4), ('Broken ankle', 4), ('Broken hand', 4), ('Unspecified', 4), ('Friend death', 4), ('Sister death', 4), ('Skin burns', 3), ('Skin cut needing stitches', 3), ('Financial ruin', 3), ('Property loss', 3), ('Sprained ankle', 3), ('Gallstones', 3), ('Family breakup', 3), ('Divorce of parents', 3), ('C-section recovery', 3), ('Love failure', 2), ('Broken finger', 2), ('Unspecified fracture', 2), ('Broken ribs', 2), ('Unspecified family death', 2), ('Broken collarbone', 2), ('Grandfather death', 2), ('Unspecified illness', 2), ('Period pain', 2), ('Being cheated', 2), ('Financial loss', 2), ('Broken tooth', 2), ('Cousin death', 2), ('Relative with cancer', 2), ('Cluster headache', 2), ('Unspecified leg problem', 2), ('Root canal', 2), ('Back pain', 2), ('Broken nose', 2), ('Aunt death', 2), ('Wisdom teeth', 2), ('Cancer (eye)', 1), ('Appendix operation', 1), ('Dislocated elbow', 1), ('Concussion', 1), ('Mono', 1), ('Sexual assault', 1), ('Kidney infection', 1), ('Hemorrhoids', 1), ('Tattoo', 1), ('Unspecified kidney problem', 1), ('Unspecified lung problem', 1), ('Unspecified cancer', 1), ('Unspecified childhood sickness', 1), ('Broken jaw', 1), ('Broken elbow', 1), ('Thrown out back', 1), ('Lost sentimental item', 1), ('Abortion', 1), ('Ruptured kidney', 1), ('Big fall', 1), ('Torn knee', 1), ('Finger hit by hammer', 1), ('Injured thumb', 1), ('Brother in law death', 1), ('Knocked teeth', 1), ('Unspecified death', 1), ('Ripping off fingernail', 1), ('Personal anger', 1), ('Wrist pain', 1), ('Getting the wind knocked out', 1), ('Blown knee', 1), ('Burst appendix', 1), ('Tooth abscess', 1), ('Tendinitis', 1), ('Altruistic frustration', 1), ('Leg operation', 1), ('Gallbladder infection', 1), ('Broken wrist', 1), ('Stomach flu', 1), ('Running away from family', 1), ('Child beating', 1), ('Sinus infection', 1), ('Broken thumb', 1), ('Family abuse', 1), ('Miscarriage', 1), ('Tooth extraction', 1), ('Feeling like your soul is lost', 1), ('Homelessness', 1), ('Losing your religion', 1), ('Losing bike', 1), ('Family member in prison', 1), ('Crohn s disease', 1), ('Irritable bowel syndrome', 1), ('Family injured', 1), ('Unspecified chronic disease', 1), ('Fibromyalgia', 1), ('Blood clot in toe', 1), ('Infected c-section', 1), ('Suicide of lover', 1), ('Dental extraction', 1), ('Unspecified partner abuse', 1), ('Infertility', 1), ('Father in law death', 1), ('Broken neck', 1), ('Scratched cornea', 1), ('Swollen lymph nodes', 1), ('Sun burns', 1), ('Tooth ache', 1), ('Lost custody of children', 1), ('Unspecified accident', 1), ('Bike accident', 1), ('Broken hip', 1), ('Not being loved by partner', 1), ('Dog bite', 1), ('Broken skull', 1)]

Base rate of mentions of best experiences:

[('Falling in love', 42), ('Children born', 41), ('Marriage', 21), ('Sex', 19), ('College graduation', 13), ('Orgasm', 11), ('Alcohol', 8), ('Vacation', 6), ('Getting job', 6), ('Personal favorite sports win', 6), ('Nature scene', 5), ('Owning home', 5), ('Sports win', 4), ('Graduating highschool', 4), ('MDMA', 4), ('Getting paid for the first time', 4), ('Amusement park', 4), ('Game of chance earning', 4), ('Job achievement', 4), ('Getting engaged', 4), ('Cannabis', 3), ('Eating favorite food', 3), ('Unexpected gift', 3), ('Moving to a better location', 3), ('Travel', 3), ('Divorce', 2), ('Gifting car', 2), ('Giving to charity', 2), ('LSD', 2), ('Won contest', 2), ('Friend reunion', 2), ('Winning bike', 2), ('Kiss', 2), ('Pet ownership', 2), ('Children', 1), ('First air trip', 1), ('First kiss', 1), ('Public performance', 1), ('Hugs', 1), ('Unspecified', 1), ('Recovering from unspecified kidney problem', 1), ('College party', 1), ('Graduate school start', 1), ('Financial success', 1), ('Dinner with loved one', 1), ('Feeling supported', 1), ('Children graduates from college', 1), ('Family event', 1), ('Participating in TV show', 1), ('Psychedelic mushrooms', 1), ('Opiates', 1), ('Having own place', 1), ('Making music', 1), ('Becoming engaged', 1), ('Theater', 1), ('Extreme sport', 1), ('Armed forces graduation', 1), ('Birthday', 1), ('Positive pregnancy test', 1), ('Feeling that God exists', 1), ('Belief that Hell does not exist', 1), ('Getting car', 1), ('Academic achievement', 1), ('Helping others', 1), ('Meeting soulmate', 1), ('Daughter back home', 1), ('Winning custody of children', 1), ('Friend stops drinking', 1), ('Masturbation', 1), ('Friend not dead after all', 1), ('Child learns to walk', 1), ('Attending wedding of loved one', 1), ('Children safe after dangerous situation', 1), ('Unspecified good news', 1), ('Met personal idol', 1), ('Child learns to talk', 1), ('Children good at school', 1)]

For clarity – “Personal favorite sports win” means that the respondent was a participant in the sport as opposed to a spectator (which was labeled as “Sports win”). The difference between “Sex” and “Orgasm” is that Sex refers to the entire act including foreplay and cuddles whereas Orgasm refers to the specific moment of climax. For some reason people would either mention one or the other, and emphasize very different aspects of the experience (e.g. intimacy vs. physical sensation) so I decided to label them differently.

*** It is possible that some fine-tuning of parameters could give rise to long-tail ratios even with a normal distribution (especially if the mean is, say, a negative value and the standard deviation is very wide). But in the general case a normal distribution will have a fairly narrow range for the ratios of the “top value divided by the second top value”. So at least as a general qualitative argument, I think, the simulations do suggest a long-tailed nature for the reported hedonic values.

Using Ibogaine to Create Friendlier Opioids

by Quintin Frerichs

Chronic Pain is a Massive, Debilitating Problem

“A new study by the CDC revealed that 50 million Americans (just under 20% of the age-adjusted adult population) suffered from chronic pain, which was defined as “pain on most days or every day in the past 6 months.” Nearly 20 million (about 7.5%) experienced high-impact chronic pain, defined as “limiting life or work activities on most days or every day in the past 6 months.”

Who Is Hurting? The Prevalence Of Chronic Pain In America

Using IHME’s GBD visualization tool, about 5% of total DALYs come from conditions associated with chronic pain (back pain, neck pain and self-harm), not to mention the implications pain has in a variety of other conditions, from osteoporosis to cancer.

The Most Effective Tool for Pain Management Carries its Own Significant Burdens

Opioids  are highly effective as analgesics for managing chronic and acute pain, and are the most widely used pain treatment[1]. However, consistent use of opioids results in tolerance, dependence, withdrawal and overdose, which claimed the lives of 47,600 people in 2017[2]. Furthermore, the CDC estimates the total economic burden of prescription opioid misuse in the US is $78.5 billion a year, including the costs of health care, lost productivity, addiction treatment, and criminal justice involvement.[4]

Finding a solution for opioids’ dark side would help millions enjoy life, reduce the global health burden by no less than 5%, avoid 10s of thousands of future deaths, and recover billions in lost productivity.

A solution may be to combine variable doses of Ibogaine, the active compound found in the Tabernanthe iboga shrub with safer classes of opioids. 

The proliferation of opioids (specifically, full mu-opioid agonists) has this laundry list of problems: tolerance, addiction, withdrawal, overdose and euphoria (if one chooses to see it as a negative side-effect). In an effort to wean off of opioids, several groups have sought to attack these symptoms. Non-opioid therapeutics include cannabidiol (CBD) and CA-008, a TRPV-1 agonist which acts on nociceptive c-fibers in the peripheral nervous system similarly to capsaicin. These tend to be less habit-forming than opioids (attributed to their lower affinity for nuclei in the mesolimbic system), but also less effective at offering relief from intense neuropathic pain[4]. Other attempts to tame opioids have been made, most of them having the reduction of pleasure as the main target. CARA Therapeutics has created a kappa-opioid agonist which acts selectively on receptors in the peripheral nervous system to “produce little to no CNS-mediated side effects that one sees with traditional CNS-acting mu opioids like nausea/vomiting, sedation, respiratory depression, abuse, addiction or euphoria”. NKTR-181, a novel full mu-opioid agonist, is more direct: “NKTR-181, a first-in-class opioid analgesic, is a new chemical entity (NCE) that is the first full mu-opioid agonist molecule designed to provide potent pain relief without the high levels of euphoria that can lead to abuse and addiction with standard opioids”. As it turns out, addiction and pleasure have a complex relationship; one is not reducible to the other[5]. Euphoria-inducing psychedelic drugs and the jhana states of meditative absorption seem to lack the addictive profile of opioids. Pleasure and habit become decoupled over time in the path of opioid addiction as well, one fading with the other stubbornly immovable. If we can have opioids that forego tolerance, addiction, withdrawal and overdose, but keep the euphoria, wouldn’t that be better?

Capsaicin_chemical_structure

Capsaicin (source)

Ibogaine has a history of being used for the treatment of opioid addiction, but it may also have interesting properties for producing safer opioids as well. While at high doses (1g+) it creates intense psychedelic effects, it also has interesting properties at both lower doses of 500-600mg and at ‘microdoses’ of around 50mg. Ibogaine is illegal in many countries, but unregulated in Mexico, legal in Brazil, Gabon, and Costa Rica, and on the prescription drug list in New Zealand and Canada. For a more in-depth review of the history of Ibogaine and its use in treatment, read this review on Pysmposia. 

In this case study, a patient who had been a long-term opioid user and recently transitioned to methadone (a replacement for harder opioids like heroin, but maintaining the full agonist mu-opioid method of action) was taken off methadone without withdrawal using increasing doses of Ibogaine (150mg, 300mg, 400mg, 500mg, 600mg). As the Ibogaine dose was increased, the methadone was halved each time. We could allow opioid users to substantially decrease their opioid intake without withdrawal, while continuing to use opioids for pain management. After a few applications at the 100-600mg level, users could be maintaining their usage at ¼ of their original intake. Then they could utilize “dirty maintenance”: taking 25-50mg of Ibogaine daily while using a much lower amount of the opioid they typically use. Microdosing ibogaine alone is also potentially mood-enhancing, and some former opioid users have employed “clean maintenance” (i.e. just Ibogaine), to reduce post-acute-withdrawal syndrome (PAWS).

The reason these solutions work is because Ibogaine acts as an ‘anti-tolerance’ drug. It potentiates the effects of opioids and prevents patterns of tolerance and dependence from forming at the neurological level. When combined with full mu-opioid agonists, even in lower doses, this can pose a risk since the dose required to overdose could be more unpredictable with Ibogaine. A ‘best of both worlds’ solution would be to continue microdosing Ibogaine in conjunction with a partial mu-opioid agonist. Partial mu-opioid agonists prevent overdose by creating an upper-bound on activity at the opioid receptor and preventing the respiratory depression that causes death in full agonists.

Agonist_2

Full vs. partial agonists (source)

While existing partial mu-opioid agonists, such as the drug combo of buprenorphine and naloxone are used in opioid replacement therapy settings, they too lack euphoria-producing properties. With this new class of analgesics, patients could choose when to start, stop, and for how long to take their pain medication without fear, along with a depression-preventing hedonic enhancement. For more, see: On Hitting the Actual Target of Hedonic Tone.

A well-known example of a partial mu-opioid agonist is 7-hydroxymitragynine, the active compound in kratom. Brazil is the only country to not prohibitively schedule either kratom or Ibogaine, and so might be an option for conducting research into this new form of non-tolerance-inducing opioid mixture. In the United States, research is being done at DemeRX for approving Ibogaine through the FDA IND process for the detoxification of people afflicted with opioid addiction. Their success would also open the door to further innovation in Ibogaine-assisted pain treatments in the US.

Risks of Ibogaine

Unfortunately, Ibogaine has a harsher risk profile than most psychedelics, and has been associated with about 30 deaths due to cardiac complications. However, many researchers who have worked with Ibogaine for decades believe that these incidents can be minimized or even eliminated by standard medical practices like employing EKG screenings. Medical screenings should not only assess current heart health, but also in-system drugs, which can be potentiated by Ibogaine use, and can lead to unexpected overdose. In a population of drug users to be treated, higher incidences of poor heart health and the presence of other drugs likely contributed to a significant number of the cases of death recorded.

Mash et al. 2018 reviewed 191 cases of ibogaine therapy (all at Dr. Mash’s clinic on Saint Kitts) and found that there were no cases of cardiac-related death at doses used for interrupting addiction. Furthermore, Clear Sky Recovery has administered 1000s of Ibogaine sessions without a single fatality.

Iboga rescheduling in the US may be far off, but its potential shouldn’t be underestimated. As Hamilton Morris notes, Ibogaine is “alien technology”, with the potential to help us humans solve some of our greatest medical mysteries. For now, it’s enough to think that it might be able to a create stable, long-term pain medication with no risk of respiratory depression, tolerance, and minimal withdrawal. Along with risk-free… risk tolerant euphoria. Whether that sustainable euphoria will be available to all, remains to be seen.


[1] https://www.mayoclinic.org/chronic-pain-medication-decisions/art-20360371

[2] https://www.hhs.gov/opioids/about-the-epidemic/index.html

[3] https://www.moveforwardpt.com/resources/detail/7-staggering-statistics-about-america-s-opioid-epi

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1920543/

[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3782756/

Featured image source: What Is Iboga?

Treating Cluster Headaches Using N,N-DMT and Other Tryptamines

by Quintin Frerichs

To extend this recent EA Forum Post, I wanted to share the results of Qualia Research Institute’s research into using tryptamines to abort and prevent cluster headaches. While the quotes and statistics contained here can provide some notion of the pain experienced by cluster headache sufferers, I think it is truly unimaginable. This report contains specific interventions to be pursued in both a philanthropic and for-profit business capacity. While for-profit options are beyond our scope, those interested in supporting philanthropic interventions should consider donating to ClusterBusters (the most important nonprofit dedicated to researching treatments for cluster headaches), or QRI (which does foundational research on ways to reduce intense suffering).

Mission: Instantly and safely abort cluster headaches and treat migraines, the #2 and #10 (respectively) most painful medical conditions according to NHS. Emphasis is placed on chronic cluster headaches, which account for as much as 80% of all clusters and currently lack an effective treatment option. 


 

I. Problem:

 

“Even child birth is 1/10th the pain of a cluster headache, seriously this name needs to change… call it ultra super migraine.” (source)

  • A back of the envelope calculation indicates there are roughly 14 thousand people enduring a cluster headache right now.[1]
  • 14.2% of US adults 18 or older reported having migraine or severe headache in the previous 3 months in the 2012 NHIS. The overall age-adjusted 3-month prevalence of migraine in females was 19.1% and in males 9.0%, but varied substantially depending on age. (source)
  • Current treatments are either ineffective, costly, unsafe, or some combination of the three. The most effective treatments available for cluster headaches include oxygen, which requires the patient to carry an oxygen tank with them at all times, and triptans, which can be used a maximum of three times daily (an issue for chronic sufferers especially) and have side effects from pain to heart attack and stroke. The most effective treatments for migraines include triptans and opioids (which have high addiction potential). Emgality, a more promising treatment for episodic cluster headaches, has recently entered the market, but its long-term risk profile and efficacy have not yet been established. 
  • Bob Wold founded “Cluster Busters” in 2002 with the explicit purpose of trying to get psychedelics to be prescription medication (see his lecture Treating Cluster Headaches with Psychedelics). He tried over 75 different prescription medications and was at the end of the rope when he found psychedelics could be helpful:
  • As noted in this Qualia Computing article, the survey surfaced that about 83% of all cluster headaches are experienced by 20% of the sufferers, most of which are classified as ‘chronic’. No existing medication has been approved for use to treat chronic cluster headaches. Vaporizing DMT could be the first such treatment, offering instant relief for cluster headaches as often as they arise in a (potentially large) percentage of sufferers.

 

II. Solution:

One of the most incredible experiences of my life was when I first aborted a CH [cluster headache] with DMT. That feeling of going from a place of excruciating pain…and feeling the pain fizzle away and die in a matter of seconds” (source)

It is known by a majority of cluster headache sufferers that psychedelics can be highly effective treatments. Due to the legal status of psychedelics, no randomized controlled trial (RCT) has been conducted, but analysis has been done on online forum responses and anonymous surveys, and interviews have been recorded. Evidence from these reports points to a number of important factors: tryptamines (the class of psychedelics which includes compounds like N,N-DMT and psilocybin, the active chemical in ‘magic mushrooms’) seem especially effective, sub-psychoactive and non-psychedelic doses can be therapeutic, and psychedelics can also decrease the frequency of headaches on long time horizons. While smoking/vaporizing is the fastest method of administration available, information from a private correspondence suggests that the FDA may be averse to approving inhalants. Intramuscular administration, utilizing Rick Strassman’s protocol, could be an alternative that would achieve rapid relief without the use of an inhalation device[2]. Since the pain being experienced is so severe, having a faster method of administration is critical. 

From the relevant academic literature:

  • The indoleamine hallucinogens, psilocybin, lysergic acid diethylamide, and lysergic acid amide, were comparable to or more efficacious than most conventional medications. These agents were also perceived to shorten/abort a cluster period and bring chronic cluster headache into remission more so than conventional medications.” (source)
  • Also, for DMT, it was suggested that singular or infrequent dosage could have potential long-term beneficial effects on headache disorders: ‘Even a single dose, or perhaps a couple, can be a lifelong benefit.’” (source)
  • “Of interest, an open-label study found that similar compounds (2-bromo-LSD) without psychedelic effect were promising for this purpose” (source)

From online surveys: 

  • A survey of members of online cluster headache forums revealed that 68% of respondents who used tryptamines had a 4 or 5 out of 5 relief. 5 indicates “completely eliminated the cluster headaches”. 
  • This survey again suggests that the main barrier to use is lack of access and hallucinogenic effects. As we found in an interview with an anonymous sufferer (see below), hallucinogenic effects may be avoidable. 
no_use_cluster_headache_difficulty_acquiring

Difficulty getting. 0 – Extremely easy to acquire, 5 – Nearly impossible to acquire

no_use_cluster_headache_legal_concern

Legal risk. 0 – Not concerned at all, 5 – Extremely concerned

no_use_cluster_headache_side_effect_concern

Side effects. 0 – Not concerned at all, 5 – Extremely concerned

From interviews with cluster headache sufferers who have tried N,N-DMT:


III. Philanthropic Opportunities

Due to the Schedule I status of psychedelics in the United States, pursuing this intervention in the US will not be feasible for a number of years (see Section IV for more information on pursuing FDA approval for DMT for cluster headaches/migraines). 

A possible solution would be to create an online education campaign publicizing the results of this report to cluster headache sufferers, designated as ‘information-only’, and pursuing the use of psychedelics to treat cluster headaches and migraines in countries where tryptamines are legal, including Brazil, Jamaica and the Netherlands. In addition, given the gravity of the disorder, it could be cost-effective to fly patients to such countries for months at a time.

While we believe that traditional metrics such as the QALY do not accurately capture the suffering caused by a cluster headache (see upcoming post on the true pain/pleasure scale), a rough QALY calculation would be as follows (focusing on chronic cluster headache sufferers rather than average, since they compromise up to 83% of total headaches[3]):

  1. Facebook AD campaign:
    1. An estimated 370,000 Americans suffer from cluster headaches, 68% of whom are on Facebook[4] (=251,000). About 15% of these suffer from chronic cluster headaches (=37,740). According to Sprout Social, the average estimated cost per click of an ad campaign is $1.72. Assuming 1/10 who click are cluster headache sufferers, to reach all chronic sufferers would take (ballpark) $650,000.
    2. Assuming about 30% of those who view the ad will pursue the treatment (rough estimate-those who put 2 or less on survey results for questions of legality, difficulty to acquire etc.) and that in 68% of cases it cured or nearly cured their clusters (based on survey results), then the resulting increase in QALYs would be (37,740 people * 0.3 * 0.68) * [0.760 (QALY coefficient) * 1 QALY – ( -0.429 (QALY coefficient)* (0.47QALY)) [5]] = $650,000/7, 404QALY = $87.70 per QALY.  
    3. These ads could also be targeted to users in countries where psilocybin and DMT are legal for use recreationally, increasing conversion rate. Further targeting could be done on Facebook groups (and other social media groups) which are associated with cluster headache treatment

IV. For-profit Opportunities 

The recent emergence of psychedelics in for-profit business settings also affords the opportunity for entrepreneurs to seek legal rescheduling of N,N-DMT in the US for the purpose of treating cluster headaches and/or migraines. Below is an outline of the process of navigating the FDA IND process, which could result in a change in legal status: 

Market Size:

‘Orphan disease’ status:  

There are two main classifications of cluster headaches, chronic and episodic. Episodic cluster headaches are characterized by periods of headaches (up to 8 times per day) of a week to a full year, which remit for periods from a month up to a year. Chronic cluster headaches, on the other hand, either last for longer than a year or have remittance periods of less than a month[6]. A meta-analysis from the NIH estimates that cluster headaches affect 124/100,000 in the U.S., meaning an estimated 370,000 people suffer from cluster headaches a year[7]. Of these, about 15%, or 60,000, suffer from chronic cluster headaches.

The FDA grants ‘orphan disease’ status to diseases which affect fewer than 200,000 persons in the U.S per year, and offers incentives to those pursuing treatments through the FDA’s IND process for such diseases, such as longer periods of exclusivity (monopoly on drug manufacture and sale) for the treatment after approval.  

  • The global market for migraine drugs (which encompasses cluster headache drugs) in 2017 was $1.7 billion.
    • Healthcare and lost productivity costs associated with migraine are estimated to be as high as $36 billion annually in the U.S. Current estimates of cluster headaches’ annual cost in the U.S. is ~$3.5 billion.
  • Share of market
    • 5 years after launch (with FDA approval, with a 5-year monopoly) – serve 20% of chronic migraine sufferers (800,000), serve 20% of cluster headache sufferers (40,000)
      • Platform’s average annual revenue per patient (migraines): $452/patient/year
        • Tryptapens – $20
        • 1g of DMT is ~$100, approximately 50 doses (although an anecdote indicate 3mg may be sufficient). Compare to triptans, at ~$115 per 9 doses. Assuming 20% markup: 
          • Chronic migraines at 20mg doses: $120/g*0.02g/dose*15 doses/month *12 months = $432/patient/year.
      • Platform’s average annual revenue per patient (cluster headache): $344/patient/year-low estimate, $6932/patient/year – high estimate
        • Tryptapen – $20
        • There is significant variance in frequency of cluster headaches: estimates range from [$120/g*0.02g/dose*30 doses/month *3 months = $324, $120/g*0.02g/dose*120 doses/month*12 months = $6912/patient/year].
      • Annual revenue, 5 years after launch: $13.6M [low cluster headache estimate] – $344M [high cluster headache estimate]
      •  Annual revenue, 5 years after launch (migraines): $344M 
    • The 5-year (or more, if ‘orphan disease’ status is gained) monopoly provided by the FDA would allow for further R&D, and as-yet undetermined projects. Some promising directions:

Why now?

  • FDA on track to approve MDMA therapy in 2021, psilocybin therapy in 2022
    1. FDA approval will catalyze a large increase in demand for psychedelic services
    2. There is sufficient evidence to attempt bringing DMT for headaches through the FDA process as it becomes increasingly open to psychedelic interventions
  • Reasons to start before FDA approval of MDMA and psilocybin:
    1. A “psychedelic renaissance” is underway: funding for psychedelic research has skyrocketed, and multiple psychedelic decriminalization initiatives (1, 2) have recently passed. Riding the current wave of activist and public support is advantageous to our efforts. 
    2. More time to build relationship with the FDA (important for seeking DMT clearance)
    3. More time to build relationships with organizations currently seeking FDA approval for therapeutic uses of psychedelics (MAPS & Compass Pathways)

Challenges: 

Regulatory:

  • Taking on the FDA IND process can be challenging and high risk from an investment standpoint. The average cost of successfully completing Phase 1-3 trials (after which the drug can be rescheduled and approved for medical use) is $100m, requires about 9-11 years and has a 6.7% success rate (private correspondence). 
    • The Multidisciplinary Association for Psychedelic Studies (MAPS) has recently raised $26.7M for Phase 3 MDMA trials alone[8]. Total, MAPS has spent in the ballpark of $30M. If Phase 3 trials demonstrate statistically-significant results, MDMA could be selectively rescheduled for use in therapeutic settings, but would require subsequent Phase 4 trials. 
  • The FDA is risk-averse and has incurred backlash from their last notable rescheduling of fentanyl in 1985[9]. Convincing the FDA to pursue rescheduling for treatment of a relatively rare disease with other available medications will likely be difficult. 
  • The success or failure of MAPS in receiving approval for MDMA will be crucial for defining the regulatory landscape for other psychedelics. Should they fail, bringing another similar substance through the process may prove much more difficult. 

Competition: 

  • As discussed in Section I, most available migraine and cluster headache drugs are ineffective, expensive, and/or have heavy risk profiles. Emgality, a new migraine drug approved last month, has received FDA ‘breakthrough therapy’ status for its ability to decrease the frequency of episodic cluster headaches and has shown promise as a palliative for migraines as well[10]. Emgality has not been approved for use in treating chronic cluster headaches, however, and does not achieve the same rapidity of administration as the DMT vape pen (see Section III). Thus, our solution is still critical for relieving symptoms instantly, and maintains the advantage of being eligible to treat chronic cluster headaches, an ‘orphan disease’. 

Business model: 

  • We would design studies to fulfill the three-step FDA drug review process:
    1. Phase 1 studies (typically involve 20 to 80 people).
    2. Phase 2 studies (typically involve a few dozen to about 300 people).
    3. Phase 3 studies (typically involve several hundred to about 3,000 people).

Use of Funds

  • Expenses for research and operations staff
    • Technicians 
    • Analysis consultants
    • Researchers with clinical experience
    • Legal counsel (paperwork)
  • Phase 1 FDA trial (our connections to expertise in the field would reduce the cost compared to average Phase 1 trials)

Data on Cost of Trials

The following information is from the MDMA/PTSD Trials led by MAPS. However, the treatment for PTSD involves: multiple therapy sessions and an MDMA-trained psychotherapist. Therapy sessions also last 6-8 hours. Presumably, some of these costs would not apply to a DMT/CH trial, so we expect trials for DMT/CH to be cheaper than the MDMA/PTSD Trials.

However, cluster headaches are not well suited to the therapeutic environment that is used to treat mental health conditions (they arise unpredictably, and require instant relief). This means there are likely significant cost-saving opportunities in the experimental design protocol.  

Summary of costs for MAPS IND Process:

Screen Shot 2019-06-06 at 12.34.09 AM


[1] Assume a world population of 7.7 billion people, and 53 out of 100,000 yearly prevalence suffering from this. Going by public health records, we see that the average number of cluster headache attacks that a sufferer experiences is about 30 a year (with a huge variance, where some people get only about 5 a year and some get them multiple times a day). Attacks last on average 1 hour (but range from 20 minutes to 3 hours). Hence, the number of people currently experiencing a CH is: 0.00053*7,700,000,000*(30/(24*365)) = 13,976.03 ~= 14 thousand

[2] Perspectives on DMT Research

[3] According to survey

[4] https://www.facebook.com/business/help/1461718327429941

[5]  For chronic sufferers, an average of between 1-8 CH per day, 1-4 hours per CH, for ~0.47 years/year having CH

[6] https://www.mayoclinic.org/diseases-conditions/cluster-headache/symptoms-causes/syc-20352080

[7] https://www.ncbi.nlm.nih.gov/pubmed/18422717

[8] https://maps.org/research/mdma/ptsd/phase3/timeline

[9] https://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf

[10] https://investor.lilly.com/news-releases/news-release-details/fda-approves-emgalityr-galcanezumab-gnlm-first-and-only

Cluster Headache Frequency Follows a Long-Tail Distribution

[Warning: Disturbing content ahead. Why talk about it? This is an ethically very serious topic and it deserves more attention. But please beware that thinking about this might be bad for one’s mental health.]


One of the key insights that shows why Effective Altruism is so important is that the positive effect on the world that results from donating to various charities follows a long-tail distribution:

health interventionsCost-effectiveness of health interventions as found in the Disease Controls Priorities Project 2. See “The moral imperative towards cost-effectiveness in global health” by Toby Ord for more explanation. [Taken from: The world’s biggest problems and why they’re not what first comes to mind]

It is for this, among other, reasons why focusing on the best interventions really pays off. Where else can we expect long-tails to appear?


In Get-Out-Of-Hell-Free Necklace we discussed how introducing a new metric into the Effective Altruist ecosystem could shed light on neglected cost-effective interventions. We presented the Hell-Index:

A country’s Hell-Index could be defined as the yearly total of people-seconds in pain and suffering that are at or above 20 in the McGill Pain Index (or equivalent)*. This index captures the intuition that intense suffering can be in some ways qualitatively different and more serious than lesser suffering in a way that isn’t really captured by a linear pain scale.

In a future article we will discuss how the quality of suffering as a function of different medical and psychological conditions very likely follows a long-tail distribution. That is, some conditions such as Cluster Headaches (which affect about 1 in 1000 people worldwide) produce pain that is orders of magnitude worse than the pain experienced in other kinds of medical conditions, such as migraines (which are themselves already described as orders of magnitude worse than tension headaches). In other words, a 0-10 pain-scale is better thought of as a logarithmic compression of the true levels of pain rather than a linear scale. So concentrating on the worst conditions could really pay off for reducing suffering in bulk amounts.

Now: the long-tailed nature of suffering may extend beyond the quality of suffering, and show up also in its quantity. That is, the frequency with which people experience episodes of intense suffering, even among those who experience the same kind of suffering, is unlikely to be normally distributed.

Intuitively, one may think that how much suffering people endure on a given year follows a normal distribution. This intuition says that if the median number of hell-seconds people endure in a year is, say, 1,000, then people who are at the 90% percentile of hell-seconds experienced per year will be experiencing something like 1,500 or at most 2,000. If suffering follows a long-tail distribution, in reality the 90% percentile might be experiencing something more akin to 10,000 hell-seconds per year, the 99% percentile something akin to 100,000, and the 99.9% something akin to 1,000,000. If true, such a heavy skew of the distribution would suggest that we should concentrate our energies on addressing the problems of the people who are unlucky to be on the upper ranges, rather than be overly concerned with “the typical person”*.

Unfortunately, I come to share the bad news that suffering probably follows a very long-tail distribution:

It is generally acknowledged that Cluster Headaches are some of the most painful experiences that people endure. Having a single Cluster Headache, lasting anywhere between 15 minutes to 4 hours, is already an ethically unacceptable situation that should never happen to begin with. It is disheartening to know that 1 in 1,000 people experience such extreme pain. But the truth of the matter is yet much worse than we intuitively think…

We recently analyzed a survey** of Cluster Headache patients that was conducted with the intention of determining the reasons why sufferers do or do not use psychedelics to relieve their pain. As it turns out, LSD, psilocybin, and DMT all get rid of Cluster Headaches in a majority of sufferers. Given the safety profile of these agents, it is insane to think that there are millions of people suffering needlessly from this condition who could be nearly-instantly cured with something as simple as growing and eating some magic mushrooms.

We will get back to this in more depth in later articles, but for the time being what we want to highlight is the responses to the question “About how many cluster headaches do you get in a typical year?”.

After cleaning the data***, we end up with 270 participants. We then ranked the values from smallest to largest, and visualize them:

270_ranked

Honestly I am a bit suspicious of the very top numbers (I do not know how you can fit 25,000 Cluster Headaches in a year, so perhaps the participant interpreted the question as “lifetime number of Cluster Headaches”). So, just to be safe, we cut the top 20 highest numbers and visualize the bottom 250 values:

first_250_

This is clearly a long-tail distribution. And since many people online do claim to have 3 or more Cluster Headaches a day, I am inclined to believe this curve. To zoom in on some parts of the distribution, here are some additional histograms that focus on the lower percentiles:

If we take the logarithm of the number of yearly Cluster Headaches, the distribution looks remarkably normal:

log_of_estimated_total_half_bins_till_12

Natural log of the responses to the question “About how many cluster headaches do you get in a typical year?”

Using a Shapiro-Wilk normalcy test does not rule out a Gaussian distribution (p >0.05). Although this in no way shows that that the distribution is log-normal (which would require more specialized statistical analysis), it is at least suggestive of it.

I should also point out that the distribution is really close to the 80/20 Pareto principle – we see that the top 20% of the participants contain about 83% of the CH incidents per year. Below you will find the percent of the total number of incidents accounted for by the bottom x% of the respondents:

  1. The bottom 10% accounts for .06% of incidents
  2. The bottom 20% accounts for 0.36% of incidents
  3. The bottom 30% accounts for .95% of incidents
  4. The bottom 40% accounts for 1.82% of incidents
  5. The bottom 50% accounts for 3.17% of incidents
  6. The bottom 60% accounts for 5.54% of incidents
  7. The bottom 70% accounts for 9.56% of incidents
  8. The bottom 80% accounts for 17% of incidents
  9. The bottom 90% accounts for 30% of incidents
  10. The bottom 95% accounts for 43% of incidents

Below we also include the number of yearly Cluster Headaches experiences at different percentiles:

  1. 10% percentile experiences 5 CH/year
  2. 20% percentile experiences 17 CH/year
  3. 30% percentile experiences 30 CH/year
  4. 40% percentile experiences 45 CH/year
  5. 50% percentile experiences 70 CH/year
  6. 60% percentile experiences 105 CH/year
  7. 70% percentile experiences 200 CH/year
  8. 80% percentile experiences 365 CH/year
  9. 90% percentile experiences 730 CH/year
  10. 95% percentile experiences 1095 CH/year
  11. 98% percentile experiences 2190 CH/year

I believe that this information is crucial to consider when assessing cost-effective interventions to help people who endure intense suffering.


Here are some additional results from the survey.

cluster_headache_tryptamine_use

The following graphs are about the beliefs and attitudes of Cluster Headache sufferers who do not use tryptamines (LSD, psilocybin, DMT, etc.) to treat their condition:

 

I think it is fair to say that the survey shows that one of the biggest barriers preventing CH patients from using tryptamines to treat their condition is simply the difficulty of acquiring them. Since a number of interviews we’ve conducted have shown that even sub-hallucinogenic doses of DMT can abort cluster headaches (writeup coming soon), more education could easily address the barrier of being concerned about hallucinogenic side effects. The social stigma seems like a minor problem, and the legal implications (the hardest to change, perhaps), are a big concern to about half of the participants (ratings of 4 or 5/5). Hence the importance of passing new laws allowing people with this condition to use them without repercussions.

Do CH sufferers who do not use tryptamines think they would work?

no_use_cluster_headache_belief_in_effectiveness

And do they work? Here is what the CH sufferers who do use them say:

use_cluster_headache_effective

Effectiveness

use_cluster_headache_kind

Tryptamines used

If we interpret a 2 or 3 in the 0 to 5 scale as an equivalent to a “maybe”, and a 4 or 5 as a “yes” to the question “do they work?” we see a big difference between non-users beliefs in their effectiveness and their reported effectiveness by users. 24% of people who use tryptamines to treat their CHs report that “They have completely eliminated the cluster headaches” and in total 68% mark it as either a 4 or a 5 in the scale (which we can interpret as “working” even if not “completely eliminating them”). This is compared to only 30% of non-users who believe the tryptamines would work. This large discrepancy also suggests that outreach and education could help sufferers give this approach a try.

Finally, we also looked at whether the users and non-users had different number of incidents per year (reasoning that perhaps those who experience more incidents would be more desperate to try legally and socially risky treatments). We notices that there is a very slight difference in the mean (and mean-log) for the number of CH incidents a year between the 20% of sufferers who treat their CHs with tryptamines and those who don’t. I won’t report the difference in the mean because the skew of the distribution makes such a metric deceptive, but the log-mean of yearly incidents of tryptamine users is 4.73 whereas for all the rest it is 4.10 (which reaches statistical significance of p < 0.05 based on a t-test). That said, we don’t think this is a very practically relevant difference. The distributions look roughly the same:

tryptamine_vs_non_tryptamine_users

The similarity between these two distributions also suggests that there is a long way to go to make sure that those who are the worse off get prompt access to tryptamines.

The End.


See also https://clusterbusters.org/, which is an organization that aims to make psychedelics legally available to people who suffer from this condition. Please consider donating to them to help this very important cause. Also consider donating to MAPS which is championing the use of psychedelics for mental health applications. Finally, consider also donating to organizations that care and strategize about how to reduce intense suffering, such as: QRI, FRIOPIS, and The Neuroethics Foundation.


*There are instrumental considerations here – if experiencing more than, say, 5,000 hell-seconds in a year is very likely to make you depressed and ineffective, then it might pay-off to also spend resources on keeping as many people as possible below that level. In particular, to be an effective Effective Altruist it pays off not to be heavily depressed and nihilistic.

**Thanks to Harlan Stewart for taking the initiative to conduct this survey. He advertised it on the Facebook groups and subreddits of Cluster Headache sufferers and got 371 responses.

***Some people provided numerical answers, which we used directly. Some other people provided ranges, in which case we used the middle point between the values provided (e.g. “200 to 300” was coded as “250”). Some people provided lower bounds, in which case we simply used such lower bound (e.g. “500+” was coded as “500”). We discarded the data of people who didn’t provide an answer in any of those formats – which left 270 participants. A more strict analysis that uses *only* the numerical responses results in the same observations listed above (e.g. the distribution is equally long-tailed and it appears to be log-normal).


[Cross-posted in Effective Altruism Forum]