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.

Using Ibogaine to Create Friendlier Opioids

by Quintin Frerichs

Chronic Pain is a Massive, Debilitating Problem

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

Who Is Hurting? The Prevalence Of Chronic Pain In America

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

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

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

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

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

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

Capsaicin_chemical_structure

Capsaicin (source)

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

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

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

Agonist_2

Full vs. partial agonists (source)

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

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

Risks of Ibogaine

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

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

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


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

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

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

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

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

Featured image source: What Is Iboga?

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

by Quintin Frerichs

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

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


 

I. Problem:

 

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

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

 

II. Solution:

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

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

From the relevant academic literature:

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

From online surveys: 

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

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

no_use_cluster_headache_legal_concern

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

no_use_cluster_headache_side_effect_concern

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

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


III. Philanthropic Opportunities

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

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

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

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

IV. For-profit Opportunities 

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

Market Size:

‘Orphan disease’ status:  

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

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

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

Why now?

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

Challenges: 

Regulatory:

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

Competition: 

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

Business model: 

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

Use of Funds

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

Data on Cost of Trials

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

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

Summary of costs for MAPS IND Process:

Screen Shot 2019-06-06 at 12.34.09 AM


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

[2] Perspectives on DMT Research

[3] According to survey

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

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

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

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

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

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

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

Cluster Headache Frequency Follows a Long-Tail Distribution

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


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

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

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


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

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

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

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

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

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

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

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

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

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

270_ranked

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

first_250_

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

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

log_of_estimated_total_half_bins_till_12

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

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

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

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

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

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

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


Here are some additional results from the survey.

cluster_headache_tryptamine_use

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

 

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

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

no_use_cluster_headache_belief_in_effectiveness

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

use_cluster_headache_effective

Effectiveness

use_cluster_headache_kind

Tryptamines used

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

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

tryptamine_vs_non_tryptamine_users

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

The End.


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


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

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

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


[Cross-posted in Effective Altruism Forum]

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.


earth-683436_960_720

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.

An Infinite Variety of Waste

Excerpt from The Mating Mind: How Sexual Choice Shaped the Evolution of Human Nature (2000) by Geoffrey Miller (pg. 128-129)

Zahavi’s handicap principle and the idea of condition-dependence* are different perspectives on the same thing. The handicap idea emphasizes that sexual ornaments and courtship behaviors must be costly in order to be reliable fitness indicators. Their cost can take almost any form. They can increase risk from predators by making an animal more conspicuous with bright colors. They can increase risk from germs by impairing an animal’s immune system (which many sex hormones do). They can burn up vast amounts of time and energy, like bird song. They can demand a huge effort to obtain a small gift of meat, as in human tribal hunting.

As with Veblen’s conspicuous consumption principle, the form of the cost does not matter much. What matters is the prodigious waste. The waste is what keeps the fitness indicators honest. The wastefulness of courtship is what makes it romantic. The wasteful dancing, the wasteful gift-giving, the wasteful conversation, the wasteful laughter, the wasteful foreplay, the wasteful adventures. From the viewpoint of “survival of the fittest,” the waste looks mad and pointless and maladaptive. Human courtship even looks wasteful from the viewpoint of sexual selection for non-generic benefits, because, as we shall see, the act of love considered most romantic are often those that cost the giver the most, but that bring the smallest material benefits to the receiver. However, from the viewpoint of fitness indicator theory, this waste is the most efficient and reliable way to discover someone’s fitness. Where you see conspicuous waste in nature, sexual choice has often been at work.

Every sexual ornament in every sexually reproducing species could be viewed as a different style of waste. Male humpback whales waste their energies with half-hour-long, hundred-decibel songs that they repeat all day long during the breeding season. Male weaverbirds waste their time constructing ornamental nests. Male stag beetles waste the matter and energy from their food growing huge mandibles. Male elephant seals waste a thousand pounds of their fat per breeding season fighting other elephant seals. Male lions waste countless calories copulating thirty times a day with female lions before the females will conceive. Male humans waste their time and energy getting graduate degrees, writing books, playing sports, fighting other men, painting pictures, playing jazz, and founding religious cults. These may not be conscious sexual strategies, but the underlying motivations for “achievement” and “status”- even in preference to material sources- were probably shaped by sexual selection. (Of course, the wasteful displays that seemed attractive during courtship may no longer be valued if they persist after offspring arrive- there is a trade-off between parental responsibilities and conspicuous display.)

The handicap principle suggests that in each case, sexual selection cares much more about the prodigious magnitude of the waste than about its precise form. Once the decision-making mechanisms of sexual choice get their necessary information about fitness from a sexual display, everything else about the display is just a matter of taste. This interplay between waste and taste gives evolution a lot of elbow room. In fact, every species with sexual ornaments can be viewed as a different variety of sexually selected waste. Without so many varieties of sexual waste, our planet would not be the host of so many species.


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

The Meaning Machine

Excerpt from Every Cradle Is a Grave: Rethinking the Ethics of Birth and Suicide (2014) by Sarah Perry

Suppose there were an experience machine that would give you any experience you desired. Superduper neuropsychologists could stimulate your brain so that you would think and feel you were writing a great novel, or making a friend, or reading an interesting book. All the time you would be floating in a tank, with electrodes attached to your brain. Should you plug into this machine for life, preprogramming your life’s experiences?

– Robert Nozick, Anarchy, State, and Utopia 

I believe that we should be very cautious about creating conscious beings, and I believe that the ideal number of conscious beings (and perhaps even living beings) in the universe is probably zero, for the good of those beings themselves.

Since suffering and misery are inescapable parts of life, if we are to justify creating life there must be something that outweighs suffering and misery within the space of universal judgements. Candidates generally fall into two categories. The first category is essentially hedonist: pleasure or good experiences are said to outnumber or outweigh bad experiences. This is the objection Bryan Caplan is making with his Free Disposal argument, discussed in the first chapter; assuming preferentism (that people choose what is good for them), and assuming that people have free choice in the relevant arenas, people would merely commit suicide if it were not true that the pleasure of life outweighs the suffering. And since only a million people per year commit suicide, creating life is obviously the right choice. A more subtle variation of this argument does not rely on suicide, but on a sort of imaginary survey: most people would probably report that their lives are worth living, that the good outweighs the bad, and therefore it must.

The second category of responses is that there is something valuable and meaningful about life that makes it worth living even if the bad vastly outweighs the good. In the previous chapter, we explored and categorized some of the things that people find meaningful, noting how these change according to circumstance and over time. One of the most salient features of the things that make life seem meaningful is that they frequently rely on illusion: the illusion of unchanging permanence, of a future state of happiness, of one’s ability to affect the world. It is my view that the sense of meaningfulness is itself an illusion, a cognitive phenomenon that is very adaptive for individuals and groups. This illusion is maintained by communities in order to organize the behavior of individuals, in part by easing their suffering.

One response to this is to counter that meaning is not an illusion- that there is real value in the world beyond what is experienced by living beings. Unfortunately, the proposed real and true meanings are often difficult to express in words to others who do not sense their truth. The feeling that life is meaningful is a pre-rational sensory perception that is widely shared. However, the specific meanings that people find satisfying and convincing are disparate and often contradictory. These underlying realities should make us question whether the sense that life is meaningful- or that some specific meaning can be found in life- is a true observation, or merely an illusion. The very adaptiveness of this belief, even if it were not true, must also make us suspect its veracity. The meaning realist has the further problem that no specific meaning is held by a majority of humanity; if there is one true meaning, then whatever it is, the majority of people’s lives go very badly because they do not perceive it.

Another response is that while meanings vary, it is enough that almost everyone finds some meaning in life. In other words, that sense that life is meaningful is enough to justify life, and the myriad meanings found and elaborated by individuals are all, in fact, the meaning of life. This seems to be the most common position articulated in modern post-Christian Western societies: if a person finds his life to be meaningful, then it is meaningful- even if different people find contradictory meanings in life. One person might find a sense of meaning in fighting for equality, another in ethno-nationalism, and they are both right.

This second response is actually a variation on hedonism, in that the experience of meaning, rather than the experience of pleasure, provides value. According to this view, a life of overwhelming suffering but with a deep experience of meaning might be better than a life of joy and pleasure that is internally felt to be meaningless. But ultimately, divorced from the meaning realism of the first response, this grounds meaning in subjective experience; the sense of meaning becomes another form of pleasure. The modern ideas that it is up to each individual to find meaning in life, and that this meaning justifies life, means accepting a meaning-based Experience Machine.

The things that we find to be meaningful are, in fact, miniature Experience Machines. They rely on illusion and filter the information that reaches us so that we may continue to feel that life is meaningful, or continue to search for meaning in life if it is missing. They are very useful; they help us organize our behavior, coordinate with others, and manage our emotions. In a practical sense they often make the suffering of life bearable; but, once they are recognized to be illusions, they cannot justify suffering in an abstract sense any more than pleasure can.

We need not jump into a Nozickian Experience Machine to get pleasure and a sense of meaning from intricate illusions. The Reverse Experience Machine experiment is close to the illusion we find ourselves in- if we found out we were in an Experience Machine already, would we choose to leave it for the real world? Institutions, religions, social communities, and even individual people function as Experience Machines, creating and maintaining illusions that help us feel that life is worthwhile. A meaning realist would reject the Experience Machine, but to be consistent he must also reject those aspects of life that use illusion or information filters to provide meaning. A meaning subjectivist has little ground to reject the Experience Machine. This has implications for the justification of life’s misery based on meaningfulness.


Excerpt from SUPERHAPPINESS: Ten Objections To Radical Mood-Enrichment by David Pearce

The ‘EXPERIENCE MACHINE’ objection [to engineering superhappiness with genetic technologies]

According to this objection, the prospect of “artificially” ratcheting up our hedonic set-point via biotech interventions just amounts to a version of Harvard University philosopher Robert Nozick’s hypothetical Experience Machine. Recall the short section of Anarchy, State, and Utopia (1974) where Nozick purportedly refutes ethical hedonism by asking us to imagine a utopian machine that can induce experiences of anything at all in its users at will. A full-blown Experience Machine will presumably provide superauthenticity too: its users might even congratulate themselves on having opted to remain plugged into the real world – having wisely rejected the blandishments of Experience Machine evangelists and their escapist fantasies. At any rate, given this hypothetical opportunity to witness all our dreams coming true, then most of us wouldn’t take it. Our rejection shows that we value far more than mere experiences. Sure, runs this objection, millennial neuroscience may be able to create experiences millions of times more wonderful than anything open to Darwinian minds. But so what? It’s mind-independent facts in the real world that matter – and matter in some sense to us – not false happiness.

POSSIBLE RESPONSE

This Objection isn’t fanciful. In future, technologies akin to Experience Machines will probably be technically feasible, perhaps combining immersive VR, neural nanobots and a rewiring of the pleasure centres. Such technologies may conceivably become widely available or even ubiquitous – though whether their global use could ever be sociologically and evolutionarily stable for a whole population is problematic. [If you do think Experience Machines may become ubiquitous, then you might wonder (shades of the Simulation Argument) whether statistically you’re most probably plugged into one already. This hypothesis is more compelling if you’re a life-loving optimist who thinks you’re living in the best of all possible worlds than if you’re a depressive Darwinian convinced you’re living in the unspeakably squalid basement.]

However, feasible or otherwise, Experience Machines aren’t the kind of hedonic engineering technology we’re discussing here. Genetically recalibrating our hedonic treadmill at progressively more exalted settings needn’t promote the growth of escapist fantasy worlds. Measured, incremental increase in normal hedonic tone can allow (post-)humans to engage with the world – and each other – no less intimately than before; and possibly more so. By contrast, it’s contemporary social anxiety disorders and clinical depression that are associated with behavioural suppression and withdrawal. Other things being equal, a progressively happier population will also be more socially involved – with each other and with consensus reality. At present, it’s notable that the happiest people tend to lead the fullest social lives; conversely, depressives tend to be lonely and socially isolated. Posthuman mental superhealth may indeed be inconceivably different from the world of the happiest beings alive today: meaning-saturated and vibrantly authentic to a degree we physiologically can’t imagine. Yet this wonderful outcome won’t be – or at least it needn’t be – explicable because our descendants are escapists plugged into Experience Machines, but instead because posthuman life is intrinsically wonderful.

Perhaps. The above response to the Experience Machine objection is simplistic. It oversimplifies the issues because for a whole range of phenomena, there is simply no mind-independent fact of the matter that could potentially justify Experience Machine-style objections – and deter the future use of Experience Machine-like technologies for fear of our losing touch with Reality. Compare, say, mathematical beauty with artistic beauty. If you are a mathematician, then you want not merely to experience the epiphany of solving an important equation or devising an elegant proof of a mathematical theorem. You also want that solution or proof to be really true in some deep platonic sense. But if you create, say, a sculpture or a painting, then its beauty (or conversely, its ugliness) is inescapably in the eye of the beholder; there is no mind-independent truth beyond the subjective response of one’s audience. For an aesthete who longs to experience phenomenal beauty, there simply isn’t any fact of the matter beyond the quality of experience itself. The beauty is no less real, and it certainly seems to be a fact of the world; but it is subjective. If so, then why not create the substrates of posthuman superbeauty rather than mere artistic prettiness?

There’s also a sense in which our brains already are (dysfunctional) Experience Machines. Consider dreaming. Should one take drugs to suppress REM sleep because our dreams aren’t true? Or when awake, should one’s enjoyment of a beautiful sunset be dimmed by the knowledge that secondary properties like colour are mind-dependent? [Quantum theory suggests that classical macroscopic “primary” properties as normally conceived are mind-dependent too; but that’s another story] If you had been born a monochromat who sees the world only in different shades of grey, then as a hard-nosed scientific rationalist, should you reject colour vision gene therapy on the grounds that phenomenal colours are fake – and grass isn’t intrinsically green? No, by common consent visual experience enriches us, even if, strictly speaking, we are creating reality rather than simulating and/or perceiving it. Or to give another example: what if neural enhancement technologies could controllably modify our aesthetic filters so we could see 80-year-old women as sexier than 20-year-old women? Is this perception false or inauthentic? Intuitively, perhaps so. But actually, the perception is no more or less authentic than seeing 20-year-old women of prime reproductive potential as sexier. Evolution has biased our existing perceptual filters in ways that maximised the inclusive fitness of our genes in the ancestral environment; but in future, we can optimise the well-being of their bodily vehicles (i.e. us). Gradients of well-being billions of times richer than anything humans experience are neither more nor less genuine than the greenness of grass (or the allure of Marilyn Monroe). Could such states become as common as grass? Again, I suspect so; but speculation is cheap.


Analysis

Sarah Perry argues that we already live in a meaning-based Experience Machine. David Pearce reminds us that our experience of the world is itself just a phenomenal representation of a mind-independent quantum mess, and that what makes us feel good or bad is merely a reflection of what increases or decreases the inclusive fitness of our genes. In both cases, Nozick’s Experience Machine thought-experiment is turned on its head. Namely, that if we value life, we are inescapably already agreeing to living on an Experience Machine of sorts.

It is hard for me not to roll my eyes when someone says “I am not looking for happiness; I’m looking for meaning.” Although perhaps not obvious to everyone, the way in which your world-simulation is implemented is such that activities that foster the inclusive fitness of your genes feel good, while those that bring fewer future copies of your genes generally feel bad. Thanks to our neocortex, we are able to “encephalize” our deep primal emotions and render them in conjunction with (and indeed phenomenally embedded in) high-dimensional state spaces of consciousness. Key predictors of inclusive fitness such as social status, environmental stability, and the mutational load of one’s tribe are not explicitly rendered in our experience as “beneficial for your inclusive fitness.” Rather, they are rendered in a concrete simulation-congruent form (i.e. as meaningful), such as being a good person, having a home, and being able to tune in to highly evolved aesthetics, respectively. Indeed, we are adaptation executers rather than utility optimizers; the causal effect of our aesthetic preferences (e.g. preferring to think of ourselves as “meaning-seeking” rather than “pleasure-seeking”) is not legible from our subjective vintage point. But… the inherent entwining of meaning and valence (i.e. the pleasure-pain axis) is crystal clear as soon as we mess with one’s psychopharmacology, for people who fetishize meaning are not immune to mu-opioid antagonists. Unsurprisingly, it is hard to enjoy either a personal meaning, a sense of community, or even higher art while on the opioid-antagonist naltrexone. Likewise, isn’t it strange that psychedelics and empathogens seem to simultaneously increase depth of meaning and capacity for pleasure? Indeed, realizing that subjective meaning is implemented with valence gradients has extraordinary explanatory power. For this reason, it is thus clear that, as David Pearce likes to say, “if you take care of happiness, the meaning of life will take care of itself.”

What about anti-natalism? My take on anti-natalism is pretty standard for a negative leaning utilitarian and transhumanist. Namely, that selection pressures against any proclivity to self-limit human reproduction guarantees that the psychological traits that bring about hard anti-natalist views will not sustain themselves over time. If one impartially cares about the wellbeing of sentient beings, one should take into account how evolution works. Advocating for gradients of intelligent bliss rather than non-existence could satisfy anti-natalists’ craving for the absence of suffering while also being compatible with an understanding of the reality of selection pressures. Tongue-in-cheek, I thus advocate for antinatalists to have lots of children, and for pro-natalists to have no children at all. More seriously, the real solution is to develop and promote “Triple-S genetic counseling” so that every child that is born is emancipated from the agony of his or her- otherwise inevitable- future suffering.


See also: The Tyranny of the Intentional Object, Open Individualism and Antinatalism, The Purple Pill, and Consciousness vs. Pure Replicators

Frequency Specific Microcurrent for Kidney-Stone Pain

Excerpt from The Resonance Effect: How Frequency Specific Microcurrent is Changing Medicine (2017) by Carolyn McMakin 

Kidney Stone Pain

Everyone who has ever had a kidney stone will tell you that the kidney-stone pain is the worst. Emergency rooms treat it with morphine, and nothing else seems to touch it.

The phone rang on a summer Sunday morning and I hardly recognized the friend who grunted through gritted teeth to ask if “my machine” could treat kidney-stone pain. I told him that I’d never treated it before, but I’d be willing to try if he could make it to my house. He shuffled from the front door to the couch bent forward at the waist, sweating in pain. I put one wet graphite glove under his back and the other glove on his abdomen. He tried hard not to moan as I covered him with a soft blanket and placed my hand on top of the glove on his abdomen.

Education said that kidney-stone pain had to be about spasm in the ureter, the tube that carries the stone from the kidney to the bladder. The frequency for spasm was 29 hertz on channel A. The frequency for the ureter was 60 hertz on channel B. It did absolutely nothing: no warmth, no relaxation or softening, nothing. Maybe there was bleeding caused by the rough stone shredding the ureter as it traveled? I tried 18 hertz to stop bleeding on channel A. The glove didn’t get warm, and the pain didn’t change.

I really didn’t want my gray-faced friend to be my first failure. Reaching for inspiration, I tried the always-reliable 40 hertz to reduce inflammation. Nothing changed. Desperation amplified the small murmur of my intuition in my head, “Don’t get sloppy! Be thorough.”

There is a sequence of frequencies leading up to inflammation. The sequence was 20 hertz for “pressure or pain reaction,” 30 hertz for irritation, 40 hertz for inflammation. I never ran the whole sequence because 40 hertz always worked and I had no idea what a “pressure or pain reaction” might be. The buttons clicked down from 40 hertz to 20 hertz on channel A, and two things happened in seconds. The glove resting on his abdomen got hot — not just warm, it was hot. His abdomen started to soften. The feeling is hard to describe. It feels like a balloon feels when it has been sitting on the floor overnight. The tissue softens and stays soft while the correct frequency is working, and it returns to normal when the frequency is finished.

His voice was a little slurred when he fell asleep a few minutes later as he said, “Is that supposed to make me feel woozy?” His deep relaxed breathing said he was out of pain.

There are frequencies for the stone, so I tried those after twenty quiet minutes of watching him doze. The glove got hot, the abdomen softened, and ten minutes later he bolted awake and yelped, “The stone’s moving.” True to its promise, 20 hertz on A and 60 hertz on B reduced the pain again and put him back to sleep. Forty minutes later he left, pain-free, and passed the stone that night with no increase in pain.

I told this story at the Advanced Course in Australia a few weeks later, and one of the Australian practitioners reported that she treated her husband for kidney stone pain with 20 hertz on A and 60 hertz on B. He was out of pain in an hour and passed the stone uneventfully.

Every case of kidney stones treated since then has responded exactly the same way. When the patient has gripping lower back pain from lifting suitcases during a long dehydrating flight but treating the muscles doesn’t help, experience finally admits it’s not the muscle. Intuition says, “I wonder if it’s a kidney stone?” The learning curve is very steep and short when the glove gets hot, the muscles begin to relax, the pain goes down in minutes, and the patient falls asleep.

When one specific frequency combination, and only one, works every time anyone uses it, and when it does something that is otherwise impossible, then it can’t be impossible. It’s got to be resonance.

Every Child is a Genetic Experiment: FAAH Clinical Trials for Hedonic Recalibration as Educated Guesses Rather than Reckless Experimentation

by David Pearce, in response to Quora question: How do you break the hedonic treadmill?

 

The easiest pain to bear is someone else’s.
(François de La Rochefoucauld)

Could two small genetic tweaks get rid of most of the world’s mental and physical pain?
A tentative answer is: just conceivably. More cautiously, the problem of suffering should be genetically soluble this century. Before launching into a long list of caveats and complications – and outright scepticism – it’s worth considering a case study. The subject has waived anonymity.

Jo Cameron is a retired Scottish schoolteacher, a socially responsible vegan and pillar of the local community. Jo has gone though life in a perpetual state of “mild euphoria”. She has unusually high levels of anandamide (from the Sanskrit for “bliss”) and is never anxious, though her serenity may vary. Jo doesn’t feel pain, or at least not in any sense most of us would recognise: childbirth felt like “a tickle”. She is hyperthymic, but not manic. Unlike previously reported cases of congenital analgesia, Jo didn’t die young or find the need to adopt a “cotton-wool” existence to avoid bodily trauma. She came to the attention of medical researchers only when her disdain of painkillers for what “ought” to have been an excruciating medical procedure – a trapeziectomy on her right thumb – intrigued her doctor. “I had no idea until a few years ago there was anything that unusual about how little pain I feel – I just thought it was normal.
With CRISPR genome-editing, lifelong bliss could be normal.

Jo Cameron is first known case of someone with mutations in both the FAAH gene and its newly-discovered sister gene, FAAH-OUT, which modulates the FAAH gene. The FAAH gene (short for Fatty Acid Amide Hydrolase) is a protein-coding gene responsible for degrading bioactive fatty amides, most notably the endogenous cannabinoid anandamide. Previous mutations of FAAH are known, but the FAAH-OUT gene was previously reckoned a pseudogene. Single FAAH mutations are associated with high pain-tolerance, reduced anxiety and a sunny outlook without Jo’s “extreme” syndrome of well-being. Jo’s son has the single mutation.

Other case studies may be cited. I often use (again with prior consent) the example of my transhumanist colleague Anders Sandberg (“I do have a ridiculously high hedonic set-point”) – although Anders’ pain-sensitivity lies within the normal range. The pain-modulating SCN9A gene, which has dozens of alleles conferring varying pain (in)tolerance, is much better studied (cfHow much do our pain thresholds differ?).

What biologists call the Environment of Evolutionary Adaptation (EEA) ensures such outliers are rare. Although Jo Cameron shows accelerated wound-healing, not being a “normal”, neurotic mother on the African savannah would have carried a fitness-cost. Predators are unforgiving of relaxed moms. Our sugary “wildlife documentaries” barely hint at the cruelties of Nature. Pain, fear and anxiety are intimately linked. “Only the paranoid survive”, said Intel boss Andy Grove; and this bleak diagnosis can be true of market capitalism to this day. But we are not living on the African savannah – or even in a world of unfettered free markets. Looking ahead, all kinds of risks can be offloaded to artificial intelligence. AI and smart prostheses can potentially manage risks moreeffectively than bias-ridden humans. Intuitively, for sure, tampering with our reward circuitry will be hazardous. Genetically modifying or creating superhappy organisms with relative pain-insensitivity and enhanced zest for life will lead to increased personal risk-taking. Yet the story is more complicated. A great deal of risky and self-destructive behaviour in today’s world involves not happy, pain-free people, but the pain-ridden, depressive and psychologically disturbed. Life-loving optimists typically value life more – and seek to preserve and protect it. Anecdotally, I don’t think it’s a coincidence that some of the happiest people I know dedicate their lives to the study and prevention of existential risk.

So a practical question arises.
Should a large, well-controlled clinical trial of CRISPR babies be launched, with some babies carrying Jo’s two mutations, others a single FAAH mutation like her son, and controls?
If the trial is successful, then the controls and (in due course) the wider human population could enjoy remedial gene-therapy to share the benefits.

One of the few publications to recognise the far-reaching significance of Jo’s case is the magazine Wired (cfCrispr Gene Editing Could One Day Cut Away Human Pain). Instead of the double mutation promising “only” better drugs to treat pain, humanity can now tackle the problem of suffering at its source.

Bioconservative critics will be appalled at the idea: “Doctor Mengele!” “Eugenics!” “Designer babies!” “Gattaca!” “Brave New World!” Being malaise-ridden is normal and natural. Creating superbabies would be hubris. Where will it lead? How do we know gene-editing won’t be used by despots to create a race of fearless superwarriors?
In more measured language, how can experimentation with the lives of sentient beings without prior informed consent be ethically justified?

Indeed. Yet all babies born today are unique and untested genetic experiments. All baby-making entails creating involuntary suffering. None of our genetic experiments first passed muster with a medical ethics committee. Any proposal to create transhuman superbabies will probably strike our descendants as genetic remediation, not enhancement. If we reject the arguments of anti-natalists, who view Darwinian life as malware, then all prospective parents are committed to practising genetic experimentation – just not under that inflammatory label. So what’s at issue is not the principle of genetic innovation, only whether we should harness the new tools of CRISPR-Cas9 genome-editing to conduct our experiments more responsibly. If aspiring writers can benefit from proofreaders and editors, why not aspiring parents too – where the stakes are higher?

Your question asks about breaking the hedonic treadmill (cfWhat would people who never suffered be like?). Breaking or otherwise dismantling the hedonic treadmill is worth distinguishing from recalibration of its dial-settings. Hedonic adaptation can be broken in human and non-human animals by experimentally inducing “learned helplessness” and behavioural despair in response to chronic, uncontrollable stress. Hedonic adaptation can be broken at the other extreme by using intracranial self-stimulation of the mesolimbic dopamine system. “Wireheading” shows virtually no tolerance. Pathological cases of a broken hedonic treadmill occur “naturally” in chronic unipolar depression and, much more rarely, in euphoric unipolar mania. Attempts to cheat the hedonic treadmill via drugs are fraught with pitfalls. The most powerful mood-brighteners, namely the opioids, activate the hedonic treadmill rather than mitigate it. Some opioid users end up with a habit hundreds of times their starting dose. Natural selection did not design living organisms to be happy.

Functionally, therefore, genetic recalibration is a more fruitful strategy than abolishing the hedonic treadmill, both for the individual and society at large. For what it’s worth, I personally think we should aim for a hyperthymic civilisation built on a biology of invincible well-being. Future sentience will be underpinned by gradients of bliss. However, nothing so grandiose need be envisaged in order to warrant human CRISPR trials of happy babies. Grant some fairly modest ethical assumptions, e.g. other things being equal, intelligent moral agents should act so as to reduce the burden of suffering, or at least not wantonly add to it. For any genetic intervention that alters default hedonic tone, conserving information-sensitivity to “good” and “bad” stimuli is critical. In other words, we should aim to retain the hedonic treadmill but transform its negative feedback-mechanisms into a hedonistic treadmill – where “hedonism” is understood not in the amoral popular sense of a life of drink, drugs and debauchery, but as embracing Mill’s “higher pleasures”. Hence the hedonistic imperative. If clinical trials of superbabies go well, prospective parents world-wide could be offered the opportunity to have happy, heathy babies via CRISPR genome-editing, preimplantation genetic screening and counselling.

A biohappiness revolution would be extremely cost-effective. Depression, anxiety disorders and chronic pain-syndromes significantly reduce economic growth worldwide. By conserving hedonic adaptation, but ratcheting up hedonic range and hedonic set-points, humanity can conserve and enhance empathetic understanding, social responsibility and critical insight while enriching default quality of life. By conserving hedonic adaptation, we can also conserve cherished traditional values, if so desired. Yesterday’s utopias involved overriding the preferences of others, whether for their own notional good or in pursuit of some higher cause. By contrast, elevating your pain-tolerance and raising your hedonic set-point would radically enrich your life but wouldn’t challenge your values and preferences – unless one of your core values is preserving the genetic status quo.

What could go wrong with a biohappiness revolution?
Cue for vast treatises and a sci-fi movie.
However, as well as seriously – indeed exhaustively – researching everything that could conceivably go wrong, I think we should also invesigate what could goright. The world is racked by suffering. The hedonic treadmill might more aptly be called a dolorous treadmill. Hundreds of millions of people are currently depressed, pain-ridden or both. Hundreds of billions of non-human animals are suffering too. If we weren’t so inured to a world of pain and misery, then the biosphere would be reckoned in the throes of a global medical emergency. Thanks to breakthroughs in biotechnology, pain-thresholds, default anxiety levels, hedonic range and hedonic set-points are all now adjustable parameters in human and non-human animals alike. We are living in the final century of life on Earth in which suffering is biologically inevitable. As a society, we need an ethical debate about how much pain and misery we want to preserve and create.