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!

Typical N,N-DMT Trip Progression According to an Anonymous Reader

I recently had the chance to interview someone who’s had 50+ vaporized N,N-DMT experiences. The person in question (who wishes to remain anonymous) is extremely smart, philosophically literate, and has a PhD in a STEM field from a top US university. Based on the interview notes I took, I wrote down what the progression of a “typical” experience looks like. The anonymous reader confirmed that this description provides an accurate account.


Progression for Waiting Room or Breakthrough-level DMT experiences (15-40mg range):

Onset stage (1-20 seconds): Psychedelic Molting – Sharpening of colors and edges, the world acquires a secondary layer (as if the world is “molting”), and then this second layer becomes unified and starts to resonate across the entire field of experience.pGIFjd3

Early come-up (20-40 seconds): The Hyper-Edge Capacitor – Visual field gets saturated with the Chrysanthemum, which starts to give way to 3D shapes. At this point a center of high-dimensional correlations between planes of experience starts bubbling up correlated subspaces for later use: planes, then 3D spaces, then hyper-planes, etc. And as these “high-dimensional Lego pieces” are made, they start becoming the elements of the scene (the walls, the objects, the space, the sense of presence, etc.).

Middle come-up (40-80 seconds): Crystal Worlds – In this phase of the experience there are a lot of “Buddhist no-self universes” of perfect resonance along many axes. Cave worlds, column worlds, pentagonal tiling of mirror chambers worlds, transparent blinds oceanic worlds, etc. There is a feeling that “these worlds exist independently of you” and that they are kinds of high-grade meditative states achievable by highly-attained monks and beings from other dimensions. They are sterile in some sense, though, which is that they lack evolution. They are attractor points of high-dimensional resonance. Insanely beautiful and ecstatic but also not perfect (for reasons that are hard to articulate).

Late come-up (80-100 seconds): Hyperbolic Gear World – At this point you start to see high-dimensional hyperbolic mechanisms. One intuitively feels that the state has too much energy to be contained in a Crystal World, which gives rise to stitching parallel Crystal Worlds into a unified hyperbolic world-sheet. Incredibly, this world-sheet is precise and seamless. The information contained in it is highly-specific. At this point number theory, hyperbolic geometry, and high-dimensional dynamics start to be very relevant. Irreducibly complex mathematical interlocking objects appear in very crisp and precise ways (it’s not just a fuzzy but intense impression of precision – it is a precise experience of precision clockwork machinery). 3D gear mechanisms with a prime-number of teeth that only repeat when they make as many cycles as the minimum common multiple of all the gears may show up, scenes with ‘plasma consciousness’ contained in hyperbolically-folded cavities with laminar color flow arise, spontaneous chaotic symmetry breaking devices arranged in the form of complex vibrating metallic flowers will materialize, etc. These devices also build on each other’s innovations. They can swap elements to become more interesting, more complex, more energetic, more hypnotizing, and more pleasurable than before.

Plateau (100-180 seconds): DMT Tykes – One starts to hallucinate things that are higher up in the visual hierarchy. “DMT Tykes” (another name for “DMT elves”) are humanoid forms that start to appear at this point. They are ever-evolving, and constructed of a high-dimensional hyperbolic world-sheet made of networks of interlocking Rabbit-Duck bistable percepts. In some sense the entities you see are not the DMT Tykes themselves. Instead, it feels like there are still higher-dimensional entities that interface with the space you’re at and it is those entities that control the rendered humanoid bistable percepts. The devices you saw in the immediately preceding stage (Hyperbolic Gear World) are revealed to be artifacts created by these higher-dimensional beings. As reported by others before, this space gives off the impression of being a gallery, a museum, a factory, or some kind of scientific testing facility, where entities are trying out new qualia configurations to study their properties: how they feel, what they can be used for, what it is like to experience them as a human being, etc. They are trying to compel you to take these things seriously, to see through how groundbreaking they would be for humans. Whenever one is too overwhelmed with the information presented (common misgivings are of the sort: “this is too much for a simple human” or “too beautiful, I don’t deserve this” or “what if people find out I know this?”) the experience becomes calming and things that you recognize as a human start being presented: jungles, hedonically-charged human scenes, locations, archetypes, stories about the origin of humanity, etc. And when one feels ready again to look at the complex machinery then there is this sense that the entities will continue to show you more and more of the irreducibly complex phenomenal objects native to that space.

Early comedown (180-240 seconds): High-Dimensional Breakdown – Entities may become a bit desperate to make sure they have sent along the most important information. The intensity starts subsiding and there is a lot of revisiting of earlier stages, gathering of essential insights, and decisions made about what to definitely try to bring back to one’s baseline state. Often one fears that one’s brain will never get back to normal during the earlier parts, but at this point one recognizes that there is a downward trend and that it’s all going to be ok after all. Paranoia, if present beforehand, starts to subside at this point. In terms of narrative, at this point one is usually coming to terms with what the experience will mean for your everyday life, whether you believe that the entities were real, and whether all of this was just a hallucination. The intuitive understanding that even if it is all just in your mind it still contained information of very high-value is clear at this stage (but may subside if you don’t properly encode it). Key undeniable facts of the experience at this point are: (1) there are heights of bliss and pain way outside of the range of human experience, (2) there are heights of mathematical complexity possible to experience directly that are beyond the scope of normal human cognition, and (3) there are types of qualia that matter both for intelligence and wellbeing that exist but humans are utterly clueless about. Disregarding the veracity of the entities or the literal interpretations of the experience, these three facts are straightforward to acknowledge at this stage of the trip.

Late comedown (240-360 seconds): Psychedelic Dampening – There is a clear sense that some of the information you were able to easily see and grock earlier in the experience is completely inaccessible now. You lose contact with what felt like higher forms of intelligence but you still see a lot of interesting patterns and complex geometry that you somehow realize is not as important as what happened just before. Even though it still feels like you are “very high”, it feels like one’s unique privileged access to information about consciousness is gone and that what you could discover now would not belong to the same level of “scientific breakthrough” as what you experienced before.

After-effects (360-600 seconds): Fast Sobering Up – Thinking about meta-narratives is very common at this stage, just like it is on traditional psychedelics. Things like “Where is the human world headed? What kind of consciousness will we experience as our default mode in 100 years from now? What will happen once scientists, engineers, and mathematicians start to do systematic research on the mathematics of the irreducibly-complex phenomenal objects at the peak of the experience? Etc.” Somewhere in along this stage the world finally becomes solidly uni-layered and then it just feels like a low dose of shrooms for a couple more minutes, at most.

Baseline (600 seconds onwards): Re-Grounding Stage – You start wondering what that was all about. The realization that you came back to normal again so quickly is likely to make you feel like you should have not been so afraid to try out the experience to begin with. At the same time, you also may feel a strong pull towards not experiencing that for a while (depends – some people feel braver at this point and redo the experience). In most circumstances one will feel a mood boost for several hours (up to days) for two reasons. First is the sense of significance and profundity in the form of gratitude and the feeling of being special that such an experience confers. And second, there seems to be an essentially physiological response to having gone through such an intense experience without getting harmed (if one wasn’t harmed, of course). Perhaps the annealing frame is adequate in this context. Namely, that the experience somehow smoothed out a lot of pinch points and imperfections latent in one’s psyche. The fear of “the worst that could happen to me” subsides and one experiences a sense of connection to other humans that is significantly above baseline.

Atman Retreat: Safe, Legal Psilocybin Experiences in Jamaica

Atman Retreat provides safe, legal psychedelic experiences outside of Montego Bay, Jamaica.

  • Upcoming retreat dates:
    • September 23-26 (7 spots left; as of September 2nd)
    • September 27-30 (5 spots left; as of September 2nd)
    • November 13-16
    • November 17-20
       
  • Atman recently introduced tiered pricing and a low-income ticket program.

About Atman Retreat (source)

Psychedelics are known to produce profound, meaningful, transformative experiences when used in a safe and intentional manner.1 However, many people don’t have access to psychedelics, or to a safe setting within which to use them. Others simply don’t want to break the law. Until we adopt more compassionate, evidence-based drug policy, there are few ways for people to experience these extraordinary states of consciousness safely and legally. Atman Retreat exists to fill this gap.

Our core mission is to help people explore the full potential of the psychedelic experience, in all its healing, transformative, and transcendent qualities. Retreats are held in Jamaica, where psilocybin mushrooms are legal. Participants stay at a spacious villa, with comfortable rooms and a scenic private beachfront. Our team of experienced facilitators is passionate about creating space for inner transformation, insight, and breakthroughs.

Whether you’re completely new to psychedelics, or a seasoned psychonaut interested in a different kind of journey, Atman Retreat is a complete 4-day experience that allows you to explore psychedelics safely, legally, and in a setting designed to maximize their benefits.

When you feel ready, you can apply here.



Why am I sharing this announcement? I think that Atman Retreat is especially suited to Qualia Computing readers for the following three reasons:

  1. I know some of the people who started it and I can confirm that they are good, rational, and tactful people trying to make the world a better place.
  2. The retreat is open-ended in nature. Sadly, most legal psychedelic retreats come with heavy “memetic baggage” in the form of unquestioned beliefs about spirituality or strong ideological commitments. At the very least, the focus of most legal psychedelic retreats is explicitly therapeutic. Atman Retreat is a good place to simply explore your own mind and study the nature of consciousness without having to accept any spiritual, therapeutic, or ideological framework. For example, their website has a research section which lists and summarizes recent studies on the effects of psilocybin, which shows a willingness by the staff to engage with a scientific approach to psychedelics.
  3. The participants in previous cohorts of Atman Retreat have been very aligned with both Effective Altruism and the scientific study of consciousness. In other words, the attendees are typically smart, curious, ethical, and epistemologically sound.

To this, I will add that one of the visions of the Qualia Research Institute is to create an empirical consciousness research center in which psychedelics are taken by the brightest scientists, philosophers, and engineers to explore alien state-spaces of consciousness directly.

Indeed, consciousness research is currently at a pre-Galilean state, where brain scientists refuse to “look through the telescope” so to speak (or at least if they do, they are not talking about it publicly). Scientific culture is such that discussing the EEG measurements of members of the general public under the influence of psychedelics is acceptable but as soon as one talks about one’s own direct experience with such compounds one’s scientific credibility becomes suspect.

We can change this, and one of the first steps is to establish a legal framework for consciousness researchers to be able to engage in fruitful self-experimentation. Real scientific progress on consciousness will only take place with a twin track that combines both analysis of third-person data and the use of an empirical research methodology of direct experience by the researchers themselves. By pointing to the Atman Retreat I am hoping to elevate it to the status of a sort of Schelling point for rational psychonauts to converge on for the time being.

Perhaps this is a crucial first step in establishing a legally-viable Super-Shulgin Academy* for a post-Galilean science of consciousness.

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Jamaica is waiting for you!



*From the QRI Glossary

Super-Shulgin Academy (coined by David Pearce; ref: 12345678): This is a hypothetical future intellectual society that investigates consciousness empirically. Rather than merely theorizing about it or having people from the general population describe their odd experiences, the Super-Shulgin Academy directly studies the state-space of consciousness by putting the brightest minds on the task. The Super-Shulgin Academy (1) trains high-quality consciousness researchers and psychonauts, (2) investigates the computational trade-offs between different states of consciousness, (3) finds new socially-useful applications for exotic states of consciousness, (4) practices the art and craft of creating ultra-blissful experiences, and (5) develops and maintains a full-stack memeplex that incorporates the latest insights about the state-space of consciousness into the most up-to-date Theory of Everything.

Featured image: source.

Kaleidoscopic Integration: Annealing, Symmetry, and the Information Theory of Experience

Symmetric_pattern_drifting

HP: What exactly is “symmetrical texture repetition”?

JE: Symmetrical texture repetition is just one of many complex visual distortions or alterations which consistently occur throughout psychedelic experiences on substances such as LSD, Psilocin, Ayahuasca, Mescaline, 2C-B, 2C-E and many others.

It can be described as the organization of rough textures within the external environment becoming mirrored repeatedly over its own surface in an extremely intricate and symmetrical fashion that is consistent across itself. This remains at an unchanging level of extremely high detail and visual clarity within both a person’s direct line of visual focus and peripheral vision.

 

As these repeating textures are generated they begin to give rise to a huge array of abstract forms, imagery, geometry and patterns that are perceived to be embedded within and across the symmetry.

 

Interview with Chelsea Morgan, a prolific and talented psychedelic replication artist

Towel (1)

Towel texture enhancement by Chelsea Morgan. Source.

Ice_by_Chelsea_Morgan

Ice symmetrical texture repetition by Chelsea Morgan. Source.

How it feels like to symmetry-unify from the inside, a case study:

Onion Article Headline 2016: Synesthetic Couch-Texture Not Quite Ready to Merge with Lamp Turned Space-Filling Line System, Says It Needs to Make Itself More Spiky First

 

Inside Alice’s acid-filled brain today, we are now about to experience for the 6th time or so how various blobs of textures are trying to merge into a coherent super structure. According to local sources, Alice is currently feeling a sense of awe and anticipation as the two big texture clusters in her field of vision are beginning to interact with each other. She is excited to notice that one of them is “calling” the other into it, and giving it ideas on how to “plug in geometrically” with it.

 

Alice, who reportedly took 160 micrograms of LSD roughly 3 hours ago, narrates how it felt like to make a super-symmetrical system in her visual-kinesthetic field for the 5th time:

 

“I don’t know if this was the result of alien intelligences messing up with my brain, perhaps a mystical vision about how my ancestors’ experiences connect to mine, or if it was just a strange quantum-entanglement phenomenon in consciousness currently undocumented in the scientific literature, but duude! That one time the couch texture blob made itself more spiky in order to merge with the the space-filling lamp… that was awesome. I look forward to it happening again, but now also including the carpet, walls, and my hands. Leave no texture behind – the resonant symmetry super-structure can make room for everyone.” – Said Alice, in closing.

Psychedelic Symmetry: A Window Into the Information-Theoretic Properties of Experience?

My friend Tim who had not done LSD for many years, responded to this sudden 5 hit dose by going into a state of complete dissociation. He lay down on the forest floor with glassy eyes, muttering “It is TOO beautiful! It is TOO beautiful!” and he did not respond to me, even when I stared him straight in the face. He reported afterwards that he found himself in a giant Gothic cathedral with the most extravagantly elaborate and brightly painted ornamental decorations all around him. This too can be seen as an extreme form of the regularization discussed above. Under the influence of this powerful dose, Tim’s visual brain could no longer keep up with the massive irregularity of the forest around him, and therefore presented the forest in simplified or abbreviated form, as the interior of a Gothic cathedral. It captures the large geometry of a ground plane that supports an array of vertical columns, each of which fans out high overhead to link up into an over-arching canopy of branches. The only difference is that in the Gothic cathedral the trees are in a regular geometrical array, and each one is a masterpiece of compound symmetry, composed of smaller pillars of different diameters in perfectly symmetrical arrangements, and studded with periodic patterns of ribs, ridges, or knobby protuberances as a kind of celebration of symmetry and periodicity for their own sake. There is a kind of geometrical logic expressed in the ornamental design. If part of the cathedral were lost or destroyed, the pattern could be easily restored by following the same logic as the rest of the design. In information-theoretic terms, the Gothic cathedral has lots of redundancy, its pattern could be expressed in a very much simpler compressed geometrical code. In Tim’s drug-addled brain his visual system could only muster a simple code to represent the world around him, and that is why Tim saw the forest as a Gothic cathedral. Under normal conditions, the additional information of irregularity, or how each tree and branch breaks from the strict regularity of the cathedral model of it, creates the irregular world of experience that we normally see around us. This suggests that the beautiful shapes of ornamental art are not the product of the highest human faculty, as is commonly supposed, but rather, ornamental art offers a window onto the workings of a simpler visual system, whose image of the world is distorted by artifacts of the representational scheme used in the brain. The Gothic cathedral gives a hint as to how the world might appear to a simpler creature, a lizard, or a snake, to whom the world appears more regular than it does to us, because its full irregularity is too expensive to encode exhaustively in all its chaotic details. Of course the flip-side of this rumination is that the world that we humans experience, even in the stone-cold sober state, is itself immeasurably simpler, more regular and geometric, that the real world itself, of which our experience is an imperfect replica. In the words of William Blake, “If the doors of perception were cleansed, everything would appear to man as it is, infinite.”

– “The Grand Illusion” by Cognitive Scientist Steven Lehar

960


What is the information content of a gothic cathedral? What percentage of it needs to burn down to make it impossible to reconstruct from the ruins alone?

Why Does Any of This Matter? The Deceptively Profound Implications of Psychedelic Symmetry According to Cognitive Scientist Steven Lehar

But there was one aspect of the LSD experience that had me truly baffled, and that was the fantastic symmetries and periodicities that were so characteristic of the experience. What kind of neural network model could possibly account for that? It was an issue that I grappled with for many months that stretched into years. In relation to Grossberg’s neural network, it seemed that the issue concerned the question of what happens at corners and vertices where contours meet or cross. A model based on collinearity alone would be stumped at image vertices. And yet a straightforward extension of Grossberg’s neural network theory to address image vertices leads to a combinatorial explosion. The obvious extension, initially proposed by Grossberg himself, was to posit specialized “cooperative cells” with receptive fields configured to detect and enhance other configurations of edges besides ones that are collinear. But the problem is that you would need so many different specialized cells to recognize and complete every possible type of vertex, such as T and V and X and Y vertices, where two or more edges meet at a point, and each of these vertex types would have to be replicated at every orientation, and at every location across the whole visual field! It just seemed like a brute-force solution that was totally implausible.

Then one day after agonizing for months on this issue, my LSD observations of periodic and symmetrical patterns suddenly triggered a novel inspiration. Maybe the nervous system does not require specialized hard-wired receptive fields to accomodate every type of vertex, replicated at every orientation at every spatial location. Maybe the nervous system uses something much more dynamic and adaptive and flexible. Maybe it uses circular standing waves to represent different vertex types, where the standing wave can bend and warp to match the visual input, and standing waves would explain all that symmetry and periodicity so clearly evident in the LSD experience as little rotational standing waves that emerge spontaneously at image vertices, and adapt to the configuration of those vertices. Thanks to illegal psychotropic substances, I had stumbled on a staggeringly significant new theory of the brain, a theory which, if proven right, would turn the world of neuroscience on its head! My heart raced and pounded at the implications of what I had discovered. And this theory became the prime focus of my PhD thesis (Lehar 1994), in which I did computer simulations of my harmonic resonance model that replicated certain visual illusions in a way that no other model could. I had accomplished the impossible. I had found an actual practical use and purpose for what was becoming my favorite pass-time, psychedelic drugs! It was a moment of glory for an intrepid psychonaut, a turning point in my life. Figure 2.6 shows a page from my notebook dated October 6 1992, the first mention of my new theory of harmonic resonance in the brain.

– “The Grand Illusion” by Cognitive Scientist Steven Lehar

lehar_2_6


Featured image credit: Simon Haiduk

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

Reposted from Enthea with permission from the writer: 


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

It’s great for two reasons:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

rebus-schema

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

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

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

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

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

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



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

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

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


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


Featured image credit: Michael Aaron Coleman

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.

Antoine's_Necklace_Iteration_2

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.

insula

“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:

image

(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.

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

5-MeO-DMT Trip Report by Anonymous Reader

Dose: Two 7mg hits separated by about 15 minutes.

Context: The writer of this trip report suffers from anhedonia. One of the main motivations for trying 5-MeO-DMT was to see if it could help with such anhedonia.


Oh my god. The emotion. Pure intense pain. The situation was so moving. I knew I was in a state where I couldn’t not empathize with the pain. Coming out of it I felt like I was being let in on the lesson. My social barriers weren’t formed yet and I felt like we’re all melded in one family of empathized minds. There was no hiding or not acknowledging the immensity of pain. The lesson was “This is what is possible. This is what is happening to someone. This is very serious.” But it wasn’t just that recognition. There was a social experience, almost like an induction.

The come up was physically pleasant but very fast and then became very negative and high intensity. I think if I had my normal connection to my body, I’d be gripping the chair arm in pain and grunting, possibly weeping, but one thing I noticed about the experience was that there was a lack of strength to any aversions or fears or rejections, let alone expressions thereof. In ordinary sober life, something that negative would lead me to react with aversion.

Unlike the (less) painful experience of eating habanero peppers, I regarded the experience very sincere and true. Ordinarily I’m very wary of fanaticism and sentimentalism and social pressures and tragedies of the commons etc… to the point of social and emotional non-participation in society. I realize this is pathological so I try to get past my social cynicism and inhibition. This experience definitely put me right into a state of embracing a social consensus and I had very little ability to squirm or object to whatever indoctrination I could have seen it as. From the outside a social experience looks like indoctrination, but from the inside it is genuine and true. Beneath fanaticism is genuine empathy and significance, and I realized this when coming out and crying and sighing and making other social expressions at the message I had just received, having the sense of empathy transcend all social transactions of which I’m cynical.

There was a sense of magnetism and attraction both to this blazing core of serious suffering in the peak of the experience and the beautiful blue drawing undercurrents of the high valence, lovely come down, which lasted a good 15 minutes. The content of the experience was very unified and simple. “General” is the word that I think best describes the content. It includes the ontologies normally attributed to specific concepts. It includes these but isn’t reduced to them. Very general state of thinking. “Feeling” might be a good word for the general state underlying particular “thoughts.” And perhaps it was this general freedom which added to the impression that it broke through my social cynicisms.

The part that stood out for me was the emotion. I’ve never experienced emotion that strong before and it was useful to be reminded of what emotions feel like. There are levels of intensity and depth of emotion that mustn’t be forgotten. I dream of the life where I can tap into an infinite river of significance-rich, intense emotion. I felt in the trip an endlessly self-powering current of pure emotional energy blasting away (negative in the peak) and then undertows of deep oceanic bliss emotions of wellbeing and peace in the come down. Sometimes when I’m coming off a long, multi-day fast with a meal and my hormones and neurotransmitters are changing I feel emotional. Sometimes when I’ve gone a long time without hearing music and I play some great Bach cantata really loudly, I feel a bit of that moving emotional significance again. Interestingly I didn’t really separate the intensity from the significance during the trip. They felt one and the same. All meaning and sense of echoes and ramifications and contexts seemed to simply be unified in that general unified blazing entity of pure undifferentiated intensity. Yet, it didn’t feel insignificant, even though it lacked more specific content.

I think this might help with suffering because it does two things. One is that in my experience one has little choice to resist. Embracing an experience rather than struggling with it prevents unnecessary suffering. It also gives a state of pure, undifferentiated feeling which sort of envelops pain. This is good because it shows you the “unreality” of your thoughts. When you’re in an emotional state there’s a feeling behind the thoughts and different thoughts come in to support that feeling, but contending with them individually only multiplies them. It’s easier to just address the entire feeling at once. It’s hard to say how bad that experience was when all my aversion and struggling and resisting and fighting were disabled… I couldn’t protest the experience—does that cause me to infer in my memories that it must not have been worthy of resistance and therefore dispose me to take more when really it would be suffering that I would otherwise resist and avoid in the future? All I can say was that coming out of it I was very grateful, and not grateful that it was over but grateful that I had seen such truth for the sake of truth, and then the comedown incidentally turned nice and quite pleasant.

The come-off felt very slow and beautiful. Imagine taffy hanging over a rotating disk, like a lazy Susan. It felt like I was this taffy and passing beneath me was this undertow and after a delay it would pull me under in a pulse of pleasure. Or say there’s a car and a string tied to it and on the other end your tooth, and as soon as you’d have a thought the car would start running with that string and as the slack gets pulled with the car you might get distracted but then you’d eventually have your tooth pulled and you’d have your attention brought back to a string you might not have realized was there all the time. That’s what the long delayed slow crescendo pleasantnesses of the comedown of it would do for all kinds of thoughts and images and experiential events. To find out after a long delay that all this time a thought you had several seconds ago is still going on is quite reassuring—well, in this case it was. And these tooth pulls were quite pleasurable for some reason. And along with it came the bodily sensation of being magnetically drawn toward this thing.


Since going on an SSRI in 2015 (which I discontinued after 10 months in 2015), I’ve suffered chronic anhedonia (note that this paragraph was written over a week after the experience, where most of the report was written the day after, such as the exclamatory first sentences “Oh my god. The emotion,” which I was able to express because my body was still giving me a fresh enough memory of the experience from the night before. I’ve since lost emotional connection/recollection of the experience). I find I do suffer, but I lack any sense of it mattering. In particular, there’s a lack of a coordination between my frontal lobes and my limbic system (and SSRI’s can reduce the connectivity between the limbic system and the cortex… kind of like a mild chemical frontal lobotomy…), so any complex understanding of things like life situations or future plans or anything that takes the “high road” in the fear/emotional response through the cortex, get’s processed by the cortex but not communicated to the limbic system. So I can suffer, and I can verbally understand I’m suffering, but I can’t see why that matters or why I should do anything about it. I can’t emotionally reason. I can’t envision things that excite me. I can’t come up with reasons to alleviate ongoing anxiety like I used to. Before the SSRI, I’d have a pessimistic or anxious or sad thought and then I’d intervene with reasoning and “take perspective” and realize why things are ok after all or why something IS worth doing. None of that thinking reasoning gets through now. It seems only very immediate physical things with little dependence on the cortex get a somewhat appropriate level of emotional arousal out of me, like a car accident or crudely apprehended social threats/stress. I also have lots of indecision and waste time in dull thought loops. My thoughts lack emotional potency and they fail to support decision making. The experience of 5-MeO-DMT reminded me that suffering does matter, that things do matter, there is emotional significance. Because of the state depends of memory, I can’t really access that much, though in the days following the experience my body did find a certain posture that would trigger a strong recollection of the experience. It feels like I’m in flatland and this experience is in the third dimension, the dimension of emotional significance, and my frameworks presently don’t allow me much access to these memories, but I am grateful for the experience and the long come down which allowed me to take into my cortex the verbal/generic memories of the fact emotional stuff is real, and is out there. It restored hope and reminded me of the goal of getting out of this anhedonia. It’s better to live in hope and some optimism, even if success is futile. Just look at very old or obese people who still take care of their appearance with grooming.


See also: Trip reports by anonymous Qualia Computing readers for LSD2C-B, and 4-AcO-DMT.

Get-Out-Of-Hell-Free Necklace

An approach to doing good is to come up with a metric for what constitutes good or bad, and then trying to do things that will optimally increase or decrease such metric, as the case may be.

If you do this, you have to be careful about what metric you choose.

If you have an ontology where you measure good by “number of people who feel benefited by you”, you might end up doing things like sending everyone you can a doughnut with a signed note. If instead your metric is “number of people classified as poor” you might do best to focus on interventions that get people just over the hump of poverty as defined by your scale. And so on.

Conscientious and systematic altruists tend to see problems with metrics like those above. They realize that “people impressed” and “being poor according to an economic metric” are not metrics that really carve nature at its joints.

Dissatisfied with misleading metrics, one then tends to look closer at the world and arrive at metrics that take into account the length of different lives, their quality, their instrumental effect in the world, how much are they exactly being benefited by the intervention relative to other cost-effective alternatives, and so on. And that’s how you get things like Quality Adjusted Life-Years (QALY), micromorts, and the happiness index.

This is, I think, all moving in the right direction. Metrics that make an effort to carve nature at its joints can provide new lenses to see the world. And looking through those lenses tends to generate novel angles and approaches to do a lot of good.


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This is why today I will suggest we consider a new metric: 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.

What does this metric suggest we should do to make the world better? Here is an idea (told as if narrated from the future):


Between 2030 and 2050 it was very common for people to wear Get-Out-Of-Hell-Free Necklaces. People had an incredible variety of custom-fit aesthetic and practical additives to their necklaces. But in every single one of them, you could rest assured, you would find a couple of doses of each of these agents:

  1. N,N-DMT (in case of Cluster Headaches)
  2. Quetiapine (in case of severe acute psychosis)
  3. Benzocaine + menthol (for very painful stings)
  4. Ketamine (for severe suicidal feelings)
  5. Microdosed Ibogaine + cocktail of partial mu-opioid agonists (for acute severe physical pain and panic attack, e.g.. kidney stones)

Some other people would get additional things like:

  1. Beta blocker (to take right after a traumatic event)
  2. Agmatine (to take in case you suspect of having being brainwashed recently), and
  3. Caffeine (if you absolutely need to operate heavy machinery and you are sleep-deprived)

In all cases, the antidote needed would be administered as soon as requested by the wearer. And the wearer would request the antidote as indicated by a very short test done with an app to determine the need for it.

But why? What’s this all about?

The Get-Out-Of-Hell-Free Necklace contents were chosen based on a cost-benefit analysis for how to reduce the world’s Hell-Index as much as possible. Cluster-headaches, kidney stones, bad stings, severe psychotic episodes, suicidal depression, panic attacks, and many types of acute physical pain turned out to account for a surprisingly large percentage of each country’s Hell-Index. And in many of these cases, a substantial amount of the suffering was experienced before medical help could be able to arrive to the scene and do anything about it. A lot of that intense suffering happened to be tightly concentrated in acute episodes rather than in chronic problems (save for some notable examples). And by incredible luck, it turned out that there were simple antidotes to most of these states of agony, all of them small enough to fit in a single light necklace. So it was determined that subsidizing Get-Out-Of-Hell-Free Necklaces was a no-brainer as a cost-effective altruistic intervention.


By 2050 safe and cheap genetic vaccines against almost all of these unpleasant states of consciousness had been discovered. This, in turn, made the use of the Get-Out-Of-Hell-Free Necklaces unnecessary. But many who benefited from it- who had been unlucky enough to have needed it- kept it on for many years. The piece was thought of as a symbol to commemorate humanity’s progress in the destruction of hell. An achievement certainly worth celebrating.



* Admittedly, a more refined index would also distinguish between the intensity of different types of pain/suffering above 20 in the McGill Pain Index (or equivalent). Such index would try to integrate a fair “total amount of hellish qualia” by adding up the pain of each state weighted by its most likely “true intensity” as determined by a model, and then do so for each model you have and weight the contribution of each model by its likelihood. E.g. do both a quadratic and an exponential conversion of values in the 0 to 10 visual analogue scale into dolors per second, and then do a likelihood-weighted average to combine those results into a final value.

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

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


“Dirty” Maintenance

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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