Anti-Tolerance Drugs

It would indeed be extraordinary if – alone among the neurotransmitter systems of the brain – the endogenous opioid families were immune from dysfunction. Enkephalins are critical to “basal hedonic tone” i.e. whether we naturally feel happy or sad. Yet the therapeutic implications of a recognition that dysfunctional endogenous opioid systems underlie a spectrum of anxiety-disorders and depression are too radical – at present – for the medical establishment to contemplate. In consequence, the use of opioid-based pharmacotherapies for “psychological” pain is officially taboo. The unique efficacy of opioids in banishing mental distress is neglected. Their unrivalled efficacy in treating “physical” nociceptive pain is grudgingly accepted.

 

Future Opioids, by David Pearce

Albert Camus wrote that the only serious question is whether to kill yourself or not. Tom Robbins wrote that the only serious question is whether time has a beginning and an end. Camus clearly got up on the wrong side of bed, and Robbins must have forgotten to set the alarm. There is only one serious question. And that is: Who knows how to make love stay? [emphasis mine] Answer me that and I will tell you whether or not to kill yourself.

 

– Still Life with Woodpecker by Tom Robbins

As eloquently argued by David Pearce in Future Opioids, the problem with opioids and other euphoriant drugs is not that they make you feel good, but that the positive feelings are short lived. In their stead, tolerance, withdrawal, and dependence ultimately set in after repeated use. We take the position that these negatives are not a necessary outcome of feeling free from physical or psychological malaise, for the brain has clever negative feedback mechanisms that prevent us from wireheading chemically. Rather, we believe that tackling these negative feedback mechanisms directly might be they key that unlocks never-ending bliss. Note that even if excellent anti-tolerance drugs were to be developed and commercialized for therapeutic use, we would still need to find solutions to the problems posed by wireheading. Specifically, disabling the negative feedback mechanisms in place that prevent us from feeling well all the time still leaves unsolved the problem of avoiding getting stuck in counterproductive patterns of behavior and becoming at risk of turning into a pure replicator (for proposed solutions to these problems see: Wireheading Done Right). Still, we strongly believe that finding safe and effective anti-tolerance drugs is a step in the right direction in the battle against suffering throughout the living world.

We thus provide the following list of promising anti-tolerance drugs in the hopes of: (1) piquing the interest of budding psychopharmacologists who may be weighting-in on promising research leads, (2) show a proof of concept against the fake and fatalistic truism that “what goes up has to go down” (cf. The Hedonistic Imperative), and last but not least, (3) provide hope to people suffering from physical or psychological distress who would benefit from anti-tolerance drugs, such as those who experience treatment-resistant anxiety, depression, chronic pain, or chemical dependence.

It is worth noting that this list is just a draft, and we will continue to revise it as the science progresses. Please let us know in the comment section if you are aware of compounds not included in this list (of special interest are tier 1 and tier 2 compounds).

Tier System

The list is organized by tiers. Tier 1 includes compounds for which there is evidence that they can reverse tolerance. Tier 2 deals with compounds that seem to either block or attenuate the development of tolerance, meaning that co-administering them with a euphoric agonist reduces the speed at which this euphoriant creates tolerance. Tier 3 includes potentiators. That is, compounds that enhance the effects of other substances without at the same time increasing tolerance to the extent that would be expected given the intensity of the subjective effects. Tier 4 lists compounds that, while not exactly tolerance-related, are still worth mentioning by virtue of reducing the intensity of drug withdrawals. And finally, Tier 5 includes euphoriants that have a favorable pharmacological profile relative to their alternatives, although will still produce tolerance long-term. Typically, a substance belonging to Tier X will also belong to Tier X + 1 and above (except for Tier 5) but we omit repetitions to avoid redundancy (e.g. proglumide not only reverses tolerance, but prevents tolerance, is a potentiatior, and reduces withdrawals).

Opioid System

Tier 1

  1. Ibogaine (see: Low dose treatment)
  2. Proglumide
  3. Naltrexone (specifically in Ultra Low Doses)
  4. Ibudilast (AV-411)

Tier 2

  1. Agmatine (may also help with chronic pain on its own)
  2. Curcumin (found in Turmeric; only works in high-availability forms)
  3. Thymoquinone (found in Nigella Sativa/black seed oil)

Tier 3

  1. DXM (specially potentiates the analgesia, which may be of use for chronic pain sufferers)
  2. Hydroxyzine (beware of its effects on sufferers of Akathisia/Restless Legs Syndrome; also bad in the long term for one’s cognitive capacity)
  3. L-Tyrosine
  4. Magnesium (possibly tier 2 but only weakly so)

Tier 4

  1. L-Aspartic Acid
  2. Ashwagandha
  3. JDTic
  4. Gabapentin
  5. Clonidine

Tier 5

  1. Tianeptine (its effects on the delta opioid receptor attenuates its tolerance when used in therapeutic doses)
  2. Mitragynine (thanks to its partial agonism rather than full agonism it is less dangerous in high doses relative to alternatives; specifically, mitragyne does not have dangerous respiratory depression properties on its own, so switching heroin addicts to it would arguably save countless lives)

 

GABA System

Tier 1

  1. Flumazenil (note: very dose-dependent)

Tier 2

  1. Tranylcypromine
  2. Ginsenosides
  3. Homotaurine
  4. Fasoracetam

Tier 3

  1. Dihydromyricetin

See also.

Dopamine System

Insufficient datapoints for a tier system. Here are the few promising leads:

  1. D-serin
  2. D-cycloserine
  3. Sulbutamine
  4. Bromantane
  5. Memantine

See also.


Tanks to Adam Karlovsky for help compiling these lists.

Connectome-Specific Harmonic Waves on LSD

The harmonics-in-connectome approach to modeling brain activity is a fascinating paradigm. I am privileged to have been at this talk in the 2017 Psychedelic Science conference. I’m extremely happy find out that MAPS already uploaded the talks. Dive in!

Below is a partial transcript of the talk. I figured that I should get it in written form in order to be able to reference it in future articles. Enjoy!

[After a brief introduction about harmonic waves in many different kinds of systems… at 7:04, Selen Atasoy]:

We applied the [principle of harmonic decomposition] to the anatomy of the brain. We made them connectome-specific. So first of all, what do I mean by the human connectome? Today thanks to the recent developments in structural neuroimaging techniques such as diffusion tensor imaging, we can trace the long-distance white matter connections in the brain. These long-distance white matter fibers (as you see in the image) connect distant parts of the brain, distant parts of the cortex. And the set of all of the different connections is called the connectome.

selen_connectome_image

Now, because we know the equation governing these harmonic waves, we can extend this principle to the human brain by simply solving the same equation on the human connectome instead of a metal plate (Chladni plates) or the anatomy of the zebra. And if you do that, we get a set of harmonic patterns, this time emerging in the cortex. And we decided to call these harmonic patterns connectome harmincs. And each of these connectome harmonic patterns are associated with a different frequency. And because they correspond to different frequencies they are all independent, and together they give you a new language, so to speak, to describe neural activity. So in the same way the harmonic patterns are building blocks of these complex patterns we see on animal coats, these connectome harmonics are the building blocks of the complex spatio-temporal patterns of neural activity.

Describing and explaining neural activity by using these connectome harmonics as brain states is really not very different than decomposing a complex musical pieces into its musical notes. It’s simply a new way of representing your data, or a new language to express it.

What is the advantage of using this new language? So why not use the state-of-the-art conventional neurimaging analysis methods? Because these connectome harmonics, by definition are the vibration modes, but applied to the anatomy of the human brain, and if you use them as brain states to express neural activity we can compute certain fundamental principles very easily such as the energy or the power.

The power would be the strength of activation of each of these states in neural activity. So how strongly that particular state contributes to neural activity. And the energy would be a combination of this strength of activation with the intrinsic energy of that particular brain state, and the intrinsic energy comes from the frequency of its vibration (in the analogy of vibration).

So in this study we looked at the power and the energy of these connectome harmonic brain states in order to explore the neural correlates of the LSD experience.

We looked at 12 healthy participants who received either 75µg of LSD (IV) or a placebo, over two sessions. These two sessions were 14 days apart in counter-balanced order. And the fMRI scans consisted of 3 eyes-closed resting states scans, each lasting 7 minutes, in the first and the third scan the participants were simply resting, eyes closed, but in the second scan they were also listening to music. And after each scan, the participants rated the intensity of certain experiences.

activity_power_energy_scans.png

So if you look at, firstly, at the total power and the total energy of each of these scans under LSD and placebo, what we see is that under LSD both the power as well as the energy of brain activity increases significantly.

And if we compute the probability of observing a certain energy value on LSD or placebo, what we see is that the peak of this probability distribution clearly shoots towards high energy values under LSD.

energy_difference

And that peak is even slightly higher in terms of probability when the subjects were listening to music. So if we interpret that peak as, in a way, the characteristic energy of a state, you can see that it shifts towards higher energy under LSD, and that this effect is intensified when listening to music.

And then we asked, which of these brain states, which of these frequencies, were actually contributing to this energy increase. So we partitioned the spectrum of all of these harmonic brain states into different parts and computed the energy of each of these partitions individually. So in total we have around 20,000 brain states. And if you look at the energy differences in LSD and placebo, what we find is that for a very narrow range of low frequencies actually these brain states were decreasing their energy on LSD. But for a very broad range of high frequencies, LSD was inducing an energy increase. So this says that LSD alters brain dynamics in a very frequency-selective manner. And it was causing high frequencies to increase their energy.

So next we looked at whether these changes we are observing in brain activity are correlated with any of the experiences that the participants themselves were having in that moment. If you look at the energy changes within the narrow range of low frequencies, we found that the energy changes in that range significantly correlated with the intensity of the experience of ego dissolution. The loss of subjective self.

ego_dissolution

And very interestingly, the same range of energy change within the same frequency range also significantly correlated with the intensity of emotional arousal, whether the experience was positive or negative. This could be quite relevant for studies looking into potential therapeutic applications of LSD.

emotional_arousal

Next, when we look at a slightly higher range of frequencies, what we found was that the energy changes within that range significantly correlated with the positive mood.

higher_frequencies

In brief, this suggests that it’s rather the low frequency brain states which correlated with ego dissolution or with emotional arousal, and it’s the activity of higher frequencies that is correlated with the positive experiences.

Next, we wanted to check the size of the repertoire of active brain states. And if you look at the probability of activation for any brain state (so we are not distinguishing for any frequency brain states), what we observe is that the probability of a brain state being silent (zero contribution), actually decreased under LSD. And the probability of a brain state contributing very strongly, which corresponds to the tails of these distributions, were increased under LSD. So this suggests that LSD was activating more brain states simultaneously.

repertoaire

And if we go back to the music analogy that we used in the beginning, that would correspond to playing more musical notes at the same time. And it’s very interesting, because studies that have looked at improvising, those who have looked at jazz improvisation, show that improvising jazz musicians play significantly more musical notes compared to memorized play. And this is what we seem to be finding under the effect of LSD. That your brain is actually activating more of these brain states simultaneously.

cross-frequency

And it does so in a very non-random fashion. So if you look at the correlation across different frequencies. Like at the co-activation patterns, and their activation over time. You may interpret it as the “communication across various frequencies”. What we found is that for a very broad range of the spectrum, there was a higher correlation across different frequencies in their activation patterns under LSD compared to placebo.

So this really says that LSD is actually causing a reorganization, rather than a random activation of brain states. It’s expanding the repertoire of active brain states, while maintaining -or maybe better said- recreating a complex but spontaneous order. And in the musical analogy it’s really very similar to jazz improvisation, to think about it in an intuitive way.

Now, there is actually one particular situation when dynamical systems such as the brain, and systems that change their activity over time, show this type of emergence of complex order, or enhanced improvisation, enhanced repertoire of active states. And this is when they approach what is called criticality. Now, criticality is this special type of behavior, special type of dynamics, that emerges right at the transition between order and chaos. When these two (extreme) types of dynamics are in balance. And criticality is said to be “the constantly shifting battle zone between stagnation and anarchy. The one place where a complex system can be spontaneous, adaptive, and alive” (Waldrop 1992). So if a system is approaching criticality, there are very characteristic signatures that you would observed in the data, in the relationships that you plot in your data.

And one of them is -and probably the most characteristic of them- is the emergence of power laws. So what does that mean? If you plot one observable in our data, which for example, in our case would be the maximum power of a brain state, in relationship to another observable, for example, the wavenumber, or the frequency of that brain state, and you plot them in logarithmic coordinates, that would mean that if they follow power laws, they would approximate a line. And this is exactly what we observe in our data, and surprisingly for both LSD as well as for placebo, but with one very significant and remarkable difference: because the high frequencies increase their power on LSD, this distribution follows this power law, this line, way more accurately under LSD compared to placebo. And here you see the error of the fit, which is decreasing.

This suggests that LSD shoots brain dynamics further towards criticality.  The signature of criticality that we find in LSD and in placebo is way more enhanced, way more pronounced, under the effect of LSD. And we found the same effect, not only for the maximum power, but also for the mean power, as well as for the power of fluctuations.

criticality_signature

So this suggests that the criticality actually may be the principle that is underlying this emergence of complex order, and this reorganization of brain dynamics, and which leads to enhanced improvisation in brain activity.

So, to summarize briefly, what we found was that LSD increases the total power as well as total energy of brain activity. It selectively activates high frequency brain states, and it expands the repertoire or active brain states in a very non-random fashion. And the principle underlying all of these changes seems to be a reorganization of brain dynamics, right at criticality, right at the edge of chaos, or just as the balance between order and chaos. And very interestingly, the “edge of chaos”, or the edge of criticality, is said to be where “life has enough stability to sustain itself, and enough creativity to deserve the name of life” (Waldrop 1992). So I leave you with that, and thank you for your attention.

[Applauses; ends at 22:00, followed by Q&A]

ELI5 “The Hyperbolic Geometry of DMT Experiences”

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I wrote the following in response to a comment on the r/RationalPsychonaut subreddit about this DMT article I wrote some time ago. The comment in question was: “Can somebody eli5 [explain like I am 5 years old] this for me?” So here is my attempt (more like “eli12”, but anyways):

In order to explain the core idea of the article I need to convey the main takeaways of the following four things:

  1. Differential geometry,
  2. How it relates to symmetry,
  3. How it applies to experience, and
  4. How the effects of DMT turn out to be explained (in part) by changes in the curvature of one’s experience of space (what we call “phenomenal space”).

1) Differential Geometry

If you are an ant on a ball, it may seem like you live on a “flat surface”. However, let’s imagine you do the following: You advance one centimeter in one direction, you turn 90 degrees and walk another centimeter, turn 90 degrees again and advance yet another centimeter. Logically, you just “traced three edges of a square” so you cannot be in the same place from which you departed. But let’s says that you somehow do happen to arrive at the same place. What happened? Well, it turns out the world in which you are walking is not quite flat! It’s very flat from your point of view, but overall it is a sphere! So you ARE able to walk along a triangle that happens to have three 90 degree corners.

That’s what we call a “positively curved space”. There the angles of triangles add up to more than 180 degrees. In flat spaces they add up to 180. And in “negatively curved spaces” (i.e. “negative Gaussian curvature” as talked about in the article) they add up to less than 180 degrees.

oct

Eight 90-degree triangles on the surface of a sphere

So let’s go back to the ant again. Now imagine that you are walking on some surface that, again, looks flat from your restricted point of view. You walk one centimeter, then turn 90 degrees, then walk another, turn 90 degrees, etc. for a total of, say, 5 times. And somehow you arrive at the same point! So now you traced a pentagon with 90 degree corners. How is that possible? The answer is that you are now in a “negatively curved space”, a kind of surface that in mathematics is called “hyperbolic”. Of course it sounds impossible that this could happen in real life. But the truth is that there are many hyperbolic surfaces that you can encounter in your daily life. Just to give an example, kale is a highly hyperbolic 2D surface (“H2” for short). It’s crumbly and very curved. So an ant might actually be able to walk along a regular pentagon with 90-degree corners if it’s walking on kale (cf. Too Many Triangles).

kale

An ant walking on kale may infer that the world is an H2 space.

In brief, hyperbolic geometry is the study of spaces that have this quality of negative curvature. Now, how is this related to symmetry?

2) How it relates to symmetry

As mentioned, on the surface of a sphere you can find triangles with 90 degree corners. In fact, you can partition the surface of a sphere into 8 regular triangles, each with 90 degree corners. Now, there are also other ways of partitioning the surface of a sphere with regular shapes (“regular” in the sense that every edge has the same length, and every corner has the same angle). But the number of ways to do it is not infinite. After all, there’s only a handful of regular polyhedra (which, when “inflated”, are equivalent to the ways of partitioning the surface of a sphere in regular ways).

Weinberg-1-102711_jpg_630x171_crop_q85

If you instead want to partition a plane in a regular way with geometric shapes, you don’t have many options. You can partition it using triangles, squares, and hexagons. And in all of those cases, the angles on each of the vertices will add up to 360 degrees (e.g. six triangles, four squares, or thee corners of hexagons meeting at a point). I won’t get into Wallpaper groups, but suffice it to say that there are also a limited number of ways of breaking down a flat surface using symmetry elements (such as reflections, rotations, etc.).

tiling2

Regular tilings of 2D flat space

Hyperbolic 2D surfaces can be partitioned in regular ways in an infinite number of ways! This is because we no longer have the constraints imposed by flat (or spherical) geometries where the angles of shapes must add up to a certain number of degrees. As mentioned, in hyperbolic surfaces the corners of triangles add up to less than 180 degrees, so you can fit more than 6 corners of equilateral triangles at one point (and depending on the curvature of the space, you can fit up to an infinite number of them). Likewise, you can tessellate the entire hyperbolic plane with heptagons.

61b801a08a7ef2780e96e0a574b82136

Hyperbolic tiling: Each of the heptagons is just as big (i.e. this is a projection of the real thing)

On the flip side, if you see a regular partitioning of a surface, you can infer what its curvature is! For example, if you see that a surface is entirely covered with heptagons, three on each of the corners, you can be sure that you are seeing a hyperbolic surface. And if you see a surface covered with triangles such that there are only four triangles on each joint, then you know you are seeing a spherical surface. So if you train yourself to notice and count these properties in regular patterns, you will indirectly also be able to determine whether the patterns inhabit a spherical, flat, or hyperbolic space!

3) How it applies to experience

How does this apply to experience? Well, in sober states of consciousness one is usually restricted to seeing and imagining spherical and flat surfaces (and their corresponding symmetric partitions). One can of course look at a piece of kale and think “wow, that’s a hyperbolic surface” but what is impossible to do is to see it “as if it were flat”. One can only see hyperbolic surfaces as projections (i.e. where we make regular shapes look irregular so that they can fit on a flat surface) or we end up contorting the surface in a crumbly fashion in order to fit it in our flat experiential space. (Note: even sober phenomenal space happens to be based on projective geometry; but let’s not go there for now.)

4) DMT: Hyperbolizing Phenomenal Space

In psychedelic states it is common to experience whatever one looks at (or, with more stunning effects, whatever one hallucinates in a sensorially-deprived environment such as a flotation tank) as slowly becoming more and more symmetric. Symmetrical patterns are attractors in psychedelia. It’s common for people to describe their acid experiences as “a kaleidoscope of colors and meaning”. We should not be too quick to dismiss these descriptions as purely metaphorical. As you can see from the article Algorithmic Reduction of Psychedelic States as well as PsychonautWiki’s Symmetrical Texture Repetition, LSD and other psychedelics do in fact “symmetrify” the textures you experience!

8697209364_91f2ab133e_h

What gravel might look like on 150 mics of LSD (Source)

As it turns out, this symmetrification process (what we call “lowering the symmetry detection/propagation threshold”) does allow one to experience any of the possible ways of breaking down spherical and flat surfaces in regular ways (in addition to also enabling the experience of any wallpaper group!). Thus the surfaces of the objects one hallucinates on LSD (specially for Closed Eyes Visuals), are usually carpeted with patterns that have either spherical or flat symmetries (e.g. seeing honeycombs, square grids, regular triangulations, etc.; or seeing dodecahedra, cubes, etc.).

wade_symmetry_best_blank_2

17 wallpaper symmetry groups

Only on very high doses of classic psychedelics does one start to experience objects that have hyperbolic curvature. And this is where DMT becomes very relevant. Vaping it is one of the most efficient ways of achieving “unworldly levels of psychedelia”:

On DMT the “symmetry detection threshold” is reduced to such an extent that any surface you look at very quickly gets super-saturated with regular patterns. Since (for reasons we don’t understand) our brain tries to incorporate whatever shape you hallucinate into the scene as part of the scene, the result of seeing too many triangles (or heptagons, or whatever) is that your brain will “push them into the surfaces” and, in effect, turn those surfaces into hyperbolic spaces.HeptagonsIndrasPearls

Yet another part of your brain (or system of consciousness, whatever it turns out to be) recognizes that “wait, this is waaaay too curved somehow, let me try to shape it into something that could actually exist in my universe”. Hence, in practice, if you take between 10 and 20 mg of DMT, the hyperbolic surfaces you see will become bent and contorted (similar to the pictures you find in the article) just so that they can be “embedded” (a term that roughly means “to fit some object into a space without distorting its properties too much”) into your experience of the space around you.

But then there’s a critical point at which this is no longer possible: Even the most contorted embeddings of the hyperbolic surfaces you experience cannot fit any longer in your normal experience of space on doses above 20 mg, so your mind has no other choice but to change the curvature of the 3D space around you! Thus when you go from “very high on DMT” to “super high on DMT” it feels like you are traveling to an entirely new dimension, where the objects you experience do not fit any longer into the normal world of human experience. They exist in H3 (hyperbolic 3D space). And this is in part why it is so extremely difficult to convey the subjective quality of these experiences. One needs to invoke mathematical notions that are unfamiliar to most people; and even then, when they do understand the math, the raw feeling of changing the damn geometry of your experience is still a lot weirder than you could ever anticipate.

hexagon_sphere_plane_hyp_032

Anybody else want to play hyperbolic soccer? Humans vs. Entities, the match of the eon!

Note: The original article goes into more depth

Now that you understand the gist of the original article, I encourage you to take a closer look at it, as it includes content that I didn’t touch in this ELI5 (or 12) summary. It provides a granular description of the 6 levels of DMT experience (Threshold, Chrysanthemum, Magic Eye, Waiting Room, Breakthrough, and Amnesia), many pictures to illustrate the various levels as well as the particular emergent geometries, and a theoretical discussion of the various algorithmic reductions that might explain how the hyperbolization of phenomenal space takes place based on combining a series of simpler effects together.

Qualia Computing at Consciousness Hacking (June 7th 2017)

I am delighted to announce that I will be presenting at Consciousness Hacking in San Francisco on 2017/6/7 (YMD notation).

Consciousness Hacking (CoHack) is an extremely awesome community that blends a genuine interest in benevolence, scientific rationality, experiential spirituality, self-experimentation, and holistic wellbeing together with an unceasing focus on consciousness. Truth be told, CohHack is one of the reasons why I love living in the Bay Area.

Here are the relevant event links: Eventbrite, FacebookMeetup.

And the event description:


What would happen if a bliss technology capable of inducing a constant MDMA-like state of consciousness with no negative side effects were available? What makes an experience good or bad? Is happiness a spiritual trick, or is spirituality a happiness trick?

At this month’s speaker presentation, Consciousness Hacking invites Data Science Engineer, Andrés Gómez Emilsson to discuss current research, including his own, concerning the measurement of bliss, how blissful brain states can be induced, and what implications this may have on quality of life and our relationship with the world around us.

Emilsson’s research aims to create a mathematical theory of the pleasure-pain axis that can take information about a person’s brain at a given point in time and return the approximate (or even true) level of happiness and suffering for that person. Emilsson will explore two dimensions that have been studied in affective neuroscience for decades:

  • Arousal: how much energy and activation a given emotion has
  • Valence: the “feel good or feel bad” dimension of emotion

If the purpose of life is to feel happy and to make others happy, then figuring out how valence is implemented in the brain may take us a long way in that direction. Current approaches to valence, while helpful, usually don’t address the core of the problem (ie. usually just measuring the symptoms of pleasure such as the neurotransmitters that trigger it, brain regions, positive reinforcement, etc. rather than getting at the experience of pleasure itself).

A real science of valence would not only be able to integrate and explain why the things people report as pleasurable are pleasant, it would also make a precise, empirically falsifiable hypothesis about whether arbitrary brain states will feel good or bad. This is what Emilsson aims to do.

You will take away:

  • An understanding about the current scientific consensus on the nature of happiness in the brain, and why it is incomplete
  • A philosophical case for both the feasibility and desirability of a world devoid of intense suffering
  • A new candidate mathematical formula that can be used to predict the psychological wellbeing of a brain at a given point in time
  • An argument for why bliss technology that puts us in a constant MDMA-like state of consciousness with no negative side effects is likely to become available within the next two to five decades
  • The opportunity to network with other people who are serious about figuring out the meaning of life through introspection and neuroscience

About our speaker:

Andrés Gómez Emilsson was born in México City in 1990. From an early age, he developed an interest in philosophy, mathematics, and science, leading him to compete nationally and internationally in Math and Science Olympiads. At 16, his main interest was mathematics, but after an unexpected “mystical experience”, he turned his attention to consciousness and the philosophical problems that it poses. He studied Symbolic Systems with an Artificial Intelligence concentration at Stanford, and later finished a masters in Computational Psychology at the same university. During his time at Stanford he co-founded the Stanford Transhumanist Association and became good friends with transhumanist philosopher David Pearce, taking on the flag of the Hedonistic Imperative (HI). In order to pursue the long-term goals of HI, his current primary intellectual interest is to reverse-engineer the functional, biochemical and/or quantum signatures of pure bliss.

He is currently working at a Natural Language Processing company in San Francisco, creating quantitative measures of employee happiness, productivity, and ethics at companies, with the long-term intent of creating a consciousness research institute that’s also a great place to work for (i.e. one in which employees are happy, productive, and ethical). In his free time he develops psychophysical tools to study the computational properties of consciousness.

Schedule:

6:30: Check in, snacks

6:45: Structured schmoozing

6:55: Event intro and meditation

7:00: Andrés Gómez Emilsson

7:50: Break

8:00: Break-out Sessions (small group discussion)

9:00: Break-out Recap

9:15: Closing meditation

About our venue:

ECO-SYSTM is a dynamic community of creative professionals, startups, and freelancers, founded on the idea that entertainment, creativity and business can come together to offer a truly unique work experience for Bay Area professionals. Check out membership plans here: http://eco-systm.com/


 

The Penfield Mood Organ

Extract from Do Androids Dream of Electric Sheep? by Philip K. Dick (1968)

Chapter 1

A merry little surge of electricity piped by automatic alarm from the mood organ beside his bed awakened Rick Deckard. Surprised — it always surprised him to find himself awake without prior notice — he rose from the bed, stood up in his multicolored pajamas, and stretched. Now, in her bed, his wife Iran opened her gray, unmerry eyes, blinked, then groaned and shut her eyes again.

“You set your Penfield too weak”, he said to her. “I’ll reset it and you’ll be awake and — ”

“Keep your hand off my settings.” Her voice held bitter sharpness. “I don’t want to be awake.”

He seated himself beside her, bent over her, and explained softly. “If you set the surge up high enough, you’ll be glad you’re awake; that’s the whole point. At setting C it overcomes the threshold barring consciousness, as it does for me.” Friendlily, because he felt well-disposed toward the world — his setting had been at D — he patted her bare, pale shoulder.

“Get your crude cop’s hand away,” Iran said.

“I’m not a cop.” He felt irritable, now, although he hadn’t dialed for it.

“You’re worse,” his wife said, her eyes still shut. “You’re a murderer hired by the cops.”

“I’ve never killed a human being in my life.” His irritability had risen, now; had become outright hostility.

Iran said, “Just those poor andys.”

“I notice you’ve never had any hesitation as to spending the bounty money I bring home on whatever momentarily attracts your attention.” He rose, strode to the console of his mood organ. “Instead of saving,” he said, “so we could buy a real sheep, to replace that fake electric one upstairs. A mere electric animal, and me earning all that I’ve worked my way up to through the years.” At his console he hesitated between dialing for a thalamic suppressant (which would abolish his mood of rage) or a thalamic stimulant (which would make him irked enough to win the argument).

“If you dial,” Iran said, eyes open and watching, “for greater venom, then I’ll dial the same. I’ll dial the maximum and you’ll see a fight that makes every argument we’ve had up to now seem like nothing. Dial and see; just try me.” She rose swiftly, loped to the console of her own mood organ, stood glaring at him, waiting.

He sighed, defeated by her threat. “I’ll dial what’s on my schedule for today.” Examining the schedule for January 3, 2021, he saw that a businesslike professional attitude was called for. “If I dial by schedule,” he said warily, “will you agree to also?” He waited, canny enough not to commit himself until his wife had agreed to follow suit.

“My schedule for today lists a six-hour self-accusatory depression,” Iran said.

“What? Why did you schedule that?” It defeated the whole purpose of the mood organ. “I didn’t even know you could set it for that,” he said gloomily.

“I was sitting here one afternoon,” Iran said, “and naturally I had turned on Buster Friendly and His Friendly Friends and he was talking about a big news item he’s about to break and then that awful commercial came on, the one I hate; you know, for Mountibank Lead Codpieces. And so for a minute I shut off the sound. And I heard the building, this building; I heard the — ” She gestured.

“Empty apartments,” Rick said. Sometimes he heard them at night when he was supposed to be asleep. And yet, for this day and age a one-half occupied conapt building rated high in the scheme of population density; out in what had been before the war the suburbs one could find buildings entirely empty… or so he had heard. He had let the information remain secondhand; like most people he did not care to experience it directly.

“At that moment,” Iran said, “when I had the TV sound off, I was in a 382 mood; I had just dialed it. So although I heard the emptiness intellectually, I didn’t feel it. My first reaction consisted of being grateful that we could afford a Penfield mood organ. But then I realized how unhealthy it was, sensing the absence of life, not just in this building but everywhere, and not reacting — do you see? I guess you don’t. But that used to be considered a sign of mental illness; they called it ‘absence of appropriate affect.’ So I left the TV sound off and I sat down at my mood organ and I experimented. And I finally found a setting for despair.” Her dark, pert face showed satisfaction, as if she had achieved something of worth. “So I put it on my schedule for twice a month; I think that’s a reasonable amount of time to feel hopeless about everything, about staying here on Earth after everybody who’s smart has emigrated, don’t you think?”

“But a mood like that,” Rick said, “you’re apt to stay in it, not dial your way out. Despair like that, about total reality, is self-perpetuating.”

“I program an automatic resetting for three hours later,” his wife said sleekly. “A 481. Awareness of the manifold possibilities open to me in the future; new hope that — ”

“I know 481,” he interrupted. He had dialed out the combination many times; he relied on it greatly. “Listen,” he said, seating himself on his bed and taking hold of her hands to draw her down beside him, “even with an automatic cutoff it’s dangerous to undergo a depression, any kind. Forget what you’ve scheduled and I’ll forget what I’ve scheduled; we’ll dial a 104 together and both experience it, and then you stay in it while I reset mine for my usual businesslike attitude. That way I’ll want to hop up to the roof and check out the sheep and then head for the office; meanwhile I’ll know you’re not sitting here brooding with no TV.” He released her slim, long fingers, passed through the spacious apartment to the living room, which smelled faintly of last night’s cigarettes. There he bent to turn on the TV.

From the bedroom Iran’s voice came. “I can’t stand TV before breakfast.”

“Dial 888,” Rick said as the set warmed. “The desire to watch TV, no matter what’s on it.”

“I don’t feel like dialing anything at all now,” Iran said.

“Then dial 3,” he said.

“I can’t dial a setting that stimulates my cerebral cortex into wanting to dial! If I don’t want to dial, I don’t want to dial that most of all, because then I will want to dial, and wanting to dial is right now the most alien drive I can imagine; I just want to sit here on the bed and stare at the floor.” Her voice had become sharp with overtones of bleakness as her soul congealed and she ceased to move, as the instinctive, omnipresent film of great weight, of an almost absolute inertia, settled over her.

He turned up the TV sound, and the voice of Buster Friendly boomed out and filled the room. ” — ho ho, folks. Time now for a brief note on today’s weather. The Mongoose satellite reports that fallout will be especially pronounced toward noon and will then taper off, so all you folks who’ll be venturing out — ”

Appearing beside him, her long nightgown trailing wispily, Iran shut off the TV set. “Okay, I give up; I’ll dial. Anything you want me to be; ecstatic sexual bliss — I feel so bad I’ll even endure that. What the hell. What difference does it make?”

“I’ll dial for both of us,” Rick said, and led her back into the bedroom. There, at her console, he dialed 594: pleased acknowledgment of husband’s superior wisdom in all matters. On his own console he dialed for a creative and fresh attitude toward his job, although this he hardly needed; such was his habitual, innate approach without recourse to Penfield artificial brain stimulation.

 

The Forces At Work

        Recreational agents which are legal and socially sanctioned by respectable society aren’t, of course, popularly viewed as drugs at all. The nicotine addict and the alcoholic don’t think of themselves as practising psychopharmacologists; and so alas their incompetence is frequently lethal.

        Is such incompetence curable? If it is, and if the abolitionist project can be carried forward with pharmacotherapy in advance of true genetic medicine, then a number of preconditions must first be in place. A necessary and sufficient set could not possibly be listed here. It is still worth isolating and examining below several distinct yet convergent societal trends of huge potential significance.

  1. First, it must be assumed that we will continue to seek out and use chemical mood-enhancers on a massive, species-wide scale.
  2. Second, a pioneering and pharmacologically (semi-)literate elite will progressively learn to use their agents of choice in a much more effective, safe and rational manner. The whole pharmacopoeia of licensed and unlicensed medicines will be purchasable globally over the Net. As the operation of our 30,000 plus genes is unravelled, the new discipline of pharmacogenomics will allow drugs to be personally tailored to the genetic makeup of each individual. Better still, desirable states of consciousness that can be induced pharmacologically can later be pre-coded genetically.
  3. Third, society will continue to fund and support research into genetic engineering, reproductive medicine and all forms of biotechnology. This will enable the breathtaking array of designer-heavens on offer from third-millennium biomedicine to become a lifestyle choice.
  4. Fourth, the ill-fated governmental War On (some) Drugs will finally collapse under the weight of its own contradictions. Parents are surely right to be anxious about many of today’s illegal intoxicants. Yet their toxicity will no more prove a reason to give up the dream of Better Living Through Chemistry than the casualties of early modern medicine are a reason to abandon contemporary medical science for homeopathy.
  5. Fifth, the medicalisation of everyday life, and of the human predicament itself, will continue apace. All manner of currently ill-defined discontents will be medically diagnosed and classified. Our innumerable woes will be given respectable clinical labels. Mass-medicalisation will enable the big drug companies aggressively to extend their lucrative markets in medically-approved psychotropics to a widening clientele. New and improved mood-modulating alleles, and other innovative gene-therapies for mood- and intellect-enrichment, will be patented. They will be brought to market by biotechnology companies eager to cure the psychopathologies of the afflicted; and to maximise profits.
  6. Sixth, in the next few centuries an explosive proliferation of ever-more sophisticated virtual reality software products will enable millions, and then billions, of people to live out their ideal fantasies. Paradoxically, as will be seen, the triumph of sensation-driven wish-fulfilment in immersive VR will also demonstrate the intellectual bankruptcy of our old Peripheralist nostrums of social reform. Unhappiness will persist. The hedonic treadmill can’t succumb to computer software.
  7. Seventh, secularism and individualism will triumph over resurgent Islamic and Christian fundamentalism. An entitlement to lifelong well-being in this world, rather than the next, will take on the status of a basic human right.

         There are quite a few imponderables here. Futurology is not, and predictably will never become, one of the exact sciences. Conceivably, one can postulate, for instance, the global triumph of an anti-scientific theocracy. This might be in the mould of the American religious right; or even some kind of Islamic fundamentalism. Less conceivably, there might be a global victory of tender-minded humanism over the onward march of biotechnical determinism. It is also possible that non-medically-approved drug use could be curtailed, at least for a time, with intrusive personal surveillance technologies and punishments of increasingly draconian severity. Abetted by the latest convulsion of moral panic over Drugs, for example, a repressive totalitarian super-state could institute a regime of universal compulsory blood-tests for banned substances. Enforced “detoxification” in rehabilitation camps for offenders would follow.

        These scenarios and their variants are almost certainly too alarmist. Given a pervasive ethos of individualism, and the worldwide spread of hedonistic consumer-capitalism, then as soon as people discover that there is no biophysical reason on earth why they can’t be as happy as they choose indefinitely, it will be hard to stop more adventurous spirits from exploring that option. Lifelong ecstasy isn’t nearly as bad as it sounds.

David Pearce in The Hedonistic Imperative (chapter 3)

 

Psychedelic Science 2017: Take-aways, impressions, and what’s next

 

It would be impossible for me to summarize what truly went on at Psychedelic Science 2017. Since giving a fair and detailed account of all of the presentations, workshops and social events I attended is out of the question, I will restrict myself to talking about, what I see as, the core insights and take-aways from the conference (plus some additional impressions I’ll get to). In brief, the core insights are: (1) that we are on the brink of a culturally-accepted scientific revolution on the study of consciousness in which we finally navigate our way out of our current pre-Galilean understanding of the mind, (2) that the breakdown of both the extremes of nihilism and eternalism as ideological north-stars in consciousness research is about to take place (i.e. finding out that neither scientific materialism nor spirituality convey the full picture), and (3) that a new science of valence, qualia, and rational psychonautics based on the quantification of good and bad feelings is slowly making its way into the surface.

With regards to (1): It should not come as a surprise to anyone who has been paying attention that there is a psychedelic renaissance underway. Bearing extreme world-wide counter-measures against it, in so far as psychedelic and empathogenic compounds meet the required evidentiary standards of mainstream psychopharmacology as safe and effective treatments for mental illness (and they do), they will be a staple of tomorrow’s tools for mental health. It’s not a difficult gamble: the current studies being made around the world are merely providing the scientific backing of what was already known in the 60s (for psychedelics) and 80s (for MDMA). I.e. That psychedelic medicine (people love to call it that way) in the right set and setting produces outstanding clinically-relevant effect sizes.

On (2): it is very unclear what people who attended the conference believe about the nature of reality, but overall there was a strong Open Individualist undercurrent and a powerful feeling that transcendence is right next door (even the urinals had sacred geometry*). That said, the science provided a refreshing feeling of cautious nihilism. Trying to reconcile both love and science is, in my opinion, the way to go. Whether we are about to ascend to another realm or if we are about to find out about our cosmic meaninglessness, the truth is that there are a lot of more immediate things to worry about. Arguably, psychedelic experiences could be used to treat both the afflictions that come with eternalism as well as those that come from nihilism. Namely, psychedelics often make you experience the world as you believe it to be (echoing John C. Lilly’s famous words: “In the province of the mind, what one believes to be true is true or becomes true, within certain limits to be found experientially and experimentally. These limits are further beliefs to be transcended. In the mind, there are no limits…”). So if you rely on intense (but mundanely challenged) feelings of transcendence to get by, you may find out on a psychedelic experience that making a world in which what you believe is literally true does not lead to happiness and meaningfulness in the way you thought it might. Unless, of course, one believes that everything that happens is a net positive somehow (which is hard to do given the regular onslaught of meaninglessness found in everyday life), any profound realization of an ontological basis of reality (as in “a made up universe perceived as if real”) can lead to dysphoria. Nihilism can be profoundly distressing on psychedelics. Yet, as evidenced by the bulk of conscious experiences, the quality of meaningfulness in one’s experience is a continuum, neither objective nor subjective, and neither eternal nor unreal (I’m using the terminology from the book “Meaningness“, though other terminologies exist for similar concepts such as the Buddhist “middle way”, Existentialism, Pragmatism, Rationalists’ epistemic rationality, etc.).

Psychedelic veterans usually end up converging on something that has this sort of emotional texture: A bitter-sweet yet Stoic worldview that leaves an open space for all kinds of wonderful things to happen, yet remains aware of the comings and goings of happiness and fulfillment. It makes it a point to not be too preoccupied with questions of ultimate meaning. It may be that for most people it’s impossible to arrive at such wisdom without trying out (and failing in some way) to live all of their fantasies before giving up and accepting the fluxing nature of reality. In such a case, psychedelics would seem to offer us a way to accelerate our learning about the unsatisfactoriness of attachments and find the way to live in realistic joy.

That said, maybe such wisdom is not Wisdom (in the sense of being universal) since we are restricting our analysis to the human wetware as it is today.  What reason do we have to believe that the hedonic treadmill is a fundamental property of the universe? A lot of evidence suggests persistent differences in people’s hedonic set-point (often genetically influenced, as in the case of the SCN9A gene for pain thresholds), and this challenges the notion that we can’t avoid suffering. Indeed, MDMA-like states may some day be experienced at will with the use of technology (and without side effects). There may even be scientifically-derived precision-engineered ethical and freedom-expanding wireheading technology that will make our current everyday way of life look laughably uninteresting and unmeaningful in comparison.

Unfortunately, talking about this (i.e. technologically-induced hedonic recalibration) with people who need a pessimistic metaphysics of valence just to function may be considered antisocial. For example, some people seem to need spiritual theories of the pleasure-pain axis that focus on fairness (such as the doctrine of Karma) in order to feel like they are not randomly getting the shorter end of the (cosmic) stick (this sentiment usually comes together with implicit Closed Individualist convictions). Of course feeling like one is a victim is itself the result of one’s affect. This provides the perfect segway for (3):

In addition to all of the magical (but expected) fusion of art, psychotherapy, mysticism, spirituality and self-hacking that this conference attracted, I was extremely delighted to see the hints of what I think will change the world for the better like nothing else will: psychedelic valence research.

Of particular note is the work of Dráulio Barros de Araújo (“Rapid Antidepressant Effects of the Psychedelic Ayahuasca in Treatment-Resistant Depression: A Randomized Placebo-Controlled Trial”), Mendel Kaelen (“The Psychological and Neurophysiological Effects of Music in Combination with Psychedelics”), Leor Roseman (“Psilocybin-Assisted Therapy: Neural Changes and the Relationship Between Acute Peak Experience and Clinical Outcomes”), Jordi Riba (“New Findings from Ayahuasca Research: From Enhancing Mindfulness Abilities to Promoting Neurogenesis”), Selen Atasoy (“Enhanced Improvisation in Brain Processing by LSD: Exploring Neural Correlates of LSD Experience With Connectome-Specific Harmonic Waves”), Tomas Palenicek (“The Effects of Psilocybin on Perception and Dynamics of Induced EEG/fMRI Correlates of Psychedelic Experience”) and Clare Wikins (“A Novel Approach to Detoxification from Methadone Using Low, Repeated, and Cumulative Administering of Ibogaine”).

And of all of these, Selen Atasoy‘s work seems to be hitting the nail in the head the most: Her work involves looking into how psychedelics affect the overall amount of energy that each of the brain’s discrete connectome-specific resonant states has. Without giving it away (their work with LSD is still unpublished) let me just say that they found that having some extra energy in specific harmonics was predictive of the specific psychedelic effects experienced at a given point in time (including things such as emotional arousal, deeply felt positive mood, and ego dissolution).

Remarkably, this line of work is in agreement with Mike Johnson’s theoretical framework for the study of valence (as outlined in Principia Qualia). Namely, that there is a deep connection between harmony, symmetry and valence that will make sense once we figure out the mathematical structure whose formal properties are isomorphic to a subject’s phenomenology. In particular, “Valence Structuralism” would seem to be supported by the findings that relatively pure harmonic states are experienced as positive emotion. We would further predict that very pure harmonic states would have the highest level of (positive) hedonic tone (i.e. bliss). We are indeed very intrigued by the connectome-specific harmonic approach to psychedelic research and look forward to working with this paradigm in the future. It would be an understatement to say that we are also excited to see the results of applying this paradigm to study MDMA-like states of consciousness. This line of research is, above all, what makes me think that this year is the Year of Qualia (whether we have realized it or not). As it were, we are seeing the first hints of a future science of consciousness that can finally provide quantitative predictions about valence, and hence, become the first scientifically-compliant theory of ultimate value.

And now some subjective impressions about the conference…

Impressions

Psychedelic Ambiance

At its core, the conference felt extremely psychedelic in its own right. The artwork, people’s attires, the scents, the background music, etc. were all what seemed to me like expressions of an emerging style of psychedelic ambiance: A euphoric blend of MDMA-like self-assurant empathegenesis vibes (“everything will be ok”) with an LSD-like ontological sabotage to the ego entheoblasting vibes of universal oneness (“things are not what they seem/everything already always and never has happened at the same time”). Peak experiences, after all, often involve the metaphorical reconciliation of the divine and the mundane in a cosmic dance of meaning.

The Gods

In his book “Simulations of God” John C. Lilly proposes that beneath the surface of our awareness, each and every mind worships a number of seemingly transcendental values (sometimes, but not always, explicitly personified). Whether we know it or not, he argues, each and every one of us treats as if a God at least something. Whether we think there there is a “God Out There”, that “Truth is the Ultimate God”, or that “God Is The Group”, the highest node in our behavioral hierarchy is always covertly managed by our basic assumptions about reality (and what they prescribe as “intrinsically good”). The book’s table of contents is awesome; it outlines what ends up being the bulk of what humans ever care about as their ultimate values:

  1. God As the Beginning
  2. I Am God
  3. God Out There
  4. God As Him/Her/It
  5. God As The Group
  6. God As Orgasm and Sex
  7. God As Death
  8. God As Drugs
  9. God As the Body
  10. God As Money
  11. God As Righteous Wrath
  12. God As Compassion
  13. God As War
  14. God As Science
  15. God As Mystery
  16. God As the Belief, the Simulation, the Model
  17. God As the Computer
  18. God Simulating Himself
  19. God As Consciousness-without-an-Object
  20. God As Humor
  21. God As Superspace, the Ultimate Collapse into the Black Hole, the End.
  22. The Ultimate Simulation
  23. God As the Diad

Perhaps what’s most amazing about psychedelics is that they are capable of changing one’s Gods. It’s extremely common for people who take psychedelics to de-emphasize traditionalist and mainstream Gods such as 1, 3, 5, 7, 10, 11, 13, while also having experiences (and changes of mind) that push them to emphasize 2, 6, 8, 12, 14, 15, 16, 17, 18, 19, 21, 22, and 23. But one wonders, what’s the eventual steady-state? As an umbrella description of what is going on we could say that psychedelics make you more open. But where does this, ultimately, lead?

Perhaps you started out in a conservative household and a family that emphasized loyalty to the group, conformism, nationalism and traditional religious values (1, 3, 5, 7). But once you tried LSD you felt a great change in the strength of your various deep-seated inclinations. You realize that you do not want to worship anything just to fit in, just to be part of a group, and that maybe caring about money is not as important as caring about making your own meaning out of life. You now feel like you care more about mysterious things like Orgasm (6), the Mind-Body connection (9), and philosophical questions like “If I am God, why would I build a universe with suffering in it?” (2, 15, 16, 21). You maybe watch some lectures by Alan Watts and read a book by Huxley, among other counter-culture material consumed, and you might start to develop a general belief in “the transcendent” but in a way that attempts to be compatible with the fact that you and the people you love experience suffering. You fantasize with the idea that maybe all of suffering is somehow necessary for some higher cosmic purpose (18, 19, 22) to which you are only made privy every now and then. You then continue on the path of psychedelic divination, perhaps taking more than you could handle here and there, and you are made aware of incredible universes: you meet guardians, you are led to read about Theosophy, you meet archetypes of the collective psyche, and after a while your strange experience with electronic equipment on LSD makes you wonder whether telepathy (at least an energetic and emotional variant of it) could be possible after all. But you do not ever obtain “good enough evidence” that would convince anyone who is determined to be a skeptic of your glitches of the Matrix. At some point, after taking too many magic mushrooms, you end up in what seems like a sort of Buddhist Hell: Feeling like we are all One no longer feels like a fact to be excited about, but rather, this is felt as a realization that should be forgotten as soon as one has it. Don’t let the cosmic boredom set in, don’t led nihilistic monism get to your very core. But it does, and you have a bad trip, one trip that you feel you never really recovered from, and whose nature is never talked about at psychedelic gatherings. (Don’t worry, right next door someone had a bad trip whose semantic content was the exact opposite of yours yet its effects on your corresponding valence landscapes were similar, e.g. concluding that “we are all made of atoms with no purpose” may feel just as bad as believing that “we are all God, and God is bored”). So maybe psychedelic therapy is a red herring after all, you think to yourself, and we should really be looking only into compounds that both increase euphoria and obfuscate the ultimate nature of reality at the same time. “Science, we need science” -you tell yourself- “so that we can figure out what it is that consciousness truly wants, and avoid both nihilistic bad trips as well as unrealistic eternalist mania”. Perhaps we are currently about to have to figure this out as a collective intelligence: “What do we do with the fact that we are all God?” This question is now making its way in etheric undercurrents in the shared meme-space of humanity just as the psychedelic renaissance starts to unfold.

The above paragraph is just one of the various archetypical ways in which psychedelic self-exploration may progress over time for a particular person. Of course not only do people’s progression vary; people’s starting points may be different. Some people approach psychedelics with spiritual intentions, others do so with recreation in mind, others use them for psychological self-exploration, and yet others use it to try to find glitches in reality. I would love to have a quantitative assessment of how one’s starting “implicit Gods” influence the way psychedelics affect you, and how such Gods evolve over the course of more exposure to psychedelic states of consciousness. There is a lot of wisdom-amplification research to be made on this front.

Psychedelic Gods

You’re only as young as the last time you changed your mind.

– Timothy Leary

The first thing I noticed at this conference was that this is a crowd that values both love and science. The geek in me seemed to be more than welcomed in here.

While I was able to enjoy the incredible vibe of the Bicycle Day celebration (just a day before the conference), I remember thinking that evolutionary psychology (cf. Mating Mind) would have a lot to say about it. A large proportion of seemingly selfless display of psychedelic self-sacrifice (e.g. LSD mega-dosing, spiritual training, asceticism, etc.) might in fact be just sexual signaling of fitness traits such as mental and physical robustness (cf. Algorithmic Reduction of Psychedelic StatesPolitical Peacocks). It’s hard to separate the universal love from the tribal mate-selection going on at raves and parties of this nature, and at times one may even get a bit of an anti-intellectual vibe for questioning this too deeply.

At the conference, though, I could tell there was another story going on. Namely, the God of Science made a prominent appearance, giving us all a sense of genuine progress beyond the comings and goings of the eternal game of hide-and-seek as one would expect in mere neo-hippy cyber-paganist events.

The God of Science… yes… if you think about it, holding an enriched concept of “science” (in its most expansive sense possible) while simultaneously trying to hold with equal intensity and expansiveness the intent of “love for all beings”, can make strange and wonderful things happen in your mind. Of salience is the fact that there will be an intense pull towards either only experiencing thought-forms about love or only focusing on thought-forms about science. Mixing the two requires a lot of energy. It’s almost as if we were wired to only focus on one at a time. This is an effect reminiscent to the mutual inhibition between empathizing and systematizing cognitive styles, and maybe at its core, the difficulty in blending both love and science without residue is a reflection of an underlying invariant. Under the assumption that you have a limited amount of positive valence at your disposal to paint your world simulation, and that you want to achieve clarity of mind, it is possible that you will have to front-load most of that positive valence in either broad quantitative observations (systematizing) or focused feelings of specialness and intimacy (empathizing). This is why, for instance, MDMA and 2C-B are so promising for cognitive transhumanism: these compounds can give rise to experiences in which there is a huge surplus of positive valence ready to be used to paint any aspect of your world simulation with bliss qualia. Sadly, this is a property of such states of consciousness, and it cannot currently be brought into our everyday lives as it is. Without serious genetic engineering (or other valence-enhancing technologies) all we can do for now is to make use of these states of consciousness to catalyze changes in our deep-seated existential stances in order to help us get by in our half-meaningful half-meaningless everyday life.

Of course, the Holy Grail of mental health interventions would be a technology that allows us to instantiate a context-dependent level of empathogenesis in a reliable and sustainable way. When I asked people at the conference whether they thought that having “a machine that makes you feel like you are on MDMA on demand with no tolerance, impulsivity, addiction or other side effects” would be good, most people (at least 80%) said “it would be bad for humanity to have such machine”. Why? Because they think that suffering serves a higher purpose, somehow. But I would disagree. And even if they are right, I still think that there are not enough people steel-manning the case for intelligent wire-heading. It’d be silly to find out in 2200 that we could have avoided hundreds of millions of people’s suffering at no cost to our collective growth if we only had thought more carefully about the intrinsic value of suffering back in 2050 when the MDMA-machine was invented and reflexively banned.

But healthy sustainable wire-heading (let alone wire-heading done right in light of evolution-at-the-limit scenarios) is many decades away into the future anyway. So all we have for now, by way of consciousness-expanding therapies for real-life knots-and-bolts treatment-resistant human suffering is the sort of therapy paradigms discussed in the conference. Of the roughly 135 conference talks (excluding parties, networking events, and workshops) at least 100 were either only or at least primarily focused on psychedelic therapy for mental illness (cancer end-of-life anxiety, PTSD, addiction, treatment-resistant depression, etc.). As far as a strategical cultural move, this focus on treatment is a very good approach, and from a valence utilitarian point of view maybe this is indeed what we should be focusing on in 2017. But I still wish that there was a bigger presence of some other kinds of discussion. In particular, I’d love for psychedelic science to eventually make a prominent appearance in a much wider context. Any discussion about the nature of consciousness from a scientific point of view cannot overlook the peculiar consciousness-enhancing properties of psychedelics. And any discussion about ethics, life and the purpose of it all will likewise be under-informed in so far as psychedelic peak-meaningful experiences are not brought into the conversation. After all, the ethical, philosophical, and scientific significance of psychedelics is hard to overstate.

Ideally we would all organize a conference that takes the best of: 1) A steadfast resolution to figure out the problem of consciousness, such as what we can find at places like The Science of Consciousness, 2) a steadfast resolution to combine both the best of compassion and rationality in order to help as many beings as possible, as we find in places like Effective Altruism Global, and 3) a steadfast resolution to look at the most impressive pieces of evidence about the nature of the mind and valence, as can be found in places like Psychedelic Science. All in all, this would be a perfect triad, as it would combine (1) The Question (Consciousness), (2) The Purpose (Ending Suffering), and (3) The Method (Scientific Study of Highly-Energetic States of Consciousness). Rest assured, the conferences organized by the Super-Shulgin Academy will blend these three aspects into one.

The Crowd

This was a very chill crowd. The only way for me to be edgy in the social contexts that arose at Psychedelic Science 2017 was to refuse to dab with the guy next to me (and to decline the Asparagus Butternut Squash edible offered at some point), or, at its worse, trying to spark a conversation about the benefits of well-managed opioid medication treatment for chronic pain (it was a rather opioid-phobic crowd, if I may say so myself).

On the other hand, talking about one’s experience in hyperbolic phenomenal spaces while on DMT, how to secretly communicate with people on LSD, and about the use of texture analysis and synthesis for psychophysical tasks to investigate psychedelic image processing barely raised anybody’s brows. I was happy to find that some people recognized me from Qualia Computing, and more than one of them shared the thought that it would be great to see more interbreeding and cross-fertilization between the psychedelic and the rationalist communities (I can’t agree more with this sentiment).

To give you a taste of the sort of gestalt present at this event, let me share with you something. Waiting on the line for one of the parties hosted by the conference organizers I overheard someone talking about what his ketamine experiences had taught him. Curious about it, I approached him and asked him to debrief me -if at all possible -about what he had learned. He said:

The super-intelligence that I’ve encountered on my ketamine experiences is far, far, beyond human comprehension, and its main message is that everything is interconnected; it does not matter when you hear the message, but that you hear it, and unconsciously prepare for what is going to happen. We are all soon going to be part of it, and we will all be together, knowing each other at a deeper level than we have ever thought imaginable, and experience love and meaning on another level, together in a vast interdimensional ecology of benevolent minds. All of the stories that we tell ourselves about the grand human narrative are all, well, made up by our minds on our limited human level. Whatever we are coming to, whatever this future thing that we are facing is, goes beyond human cravings for transcendence, it goes beyond the sentiment of return to nature, it goes beyond science and technology, and it goes beyond every religion and contemplative practice. The complexity to be found in the super-intelligent collective being that we will become is inexpressible, but there is nothing to fear, we are it on some level already, and we will soon all realize it.

It is hard to estimate what the distribution, prevalence and resilience of beliefs about the nature of reality, consciousness, love, purpose and everything else of the people attending this conference were. As a whole, it felt remarkably diverse, though. Based on my subjective impressions, I’d suspect that like the person quoted above, about 40% of the attendees were people who genuinely believe that there is a big consciousness event that is about to happen (whether it is a collective spiritual level-breaking point, a technological Singularity, inter-dimensional aliens taking us with them, or a more mundane run-of-the-mill recursively self-improving feedback loop with genetic methods for consciousness research). Maybe about 50% seemed to be what you might call pragmatic, agnostic, and open minded people who are simply looking to find out what’s up with the field, without spiritual (or emotional) vested interested in exactly what will happen. And finally, about 10% of the attendees might be classifiable as nihilists on some or another level. While intrigued about the effects of psychedelics, they see them as dead ends or red herrings. Perhaps useful for mental health, but not likely to be a key to reality (or even a hint of a future revolution in the states of consciousness we utilize on our everyday life).

Conclusion

I am very excited with the current movement to examine psychedelics in a rational scientific framework. Ultimately, I think that we will realize that valence is a quantifiable and definite thing (cf. Valence Structuralism). Wether we are talking about humor, pain relief, transcendence, or knots-and-bolts feelings of competence, all of our positive experiences share something in common. Ultimately, I do not know whether “valence is a spiritual trick” or if “spirituality is a valence trick”, but I am confident that as a species we do not yet have the answer to these questions and that a scientific approach to them may clarify this incredibly important line of inquiry.

Sooner or later, it seems to me, we will figure out what exactly “the universe wants from us”, so to speak, and then nothing will ever be the same; psychedelic research is a powerful and promising way to make good headway in this highly desirable direction.

 

 

 

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The look from the Sunset Cruise at the Psychedelic Science 2017 Conference


*Even the bathroom urinals seemed to have sacred geometry:

 

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Even the urinals had sacred geometry… reminding you of the interconnectedness of all things at the unlikeliest of moments.

Their Scientific Significance is Hard to Overstate

I think it’s hard to overstate the cognitive significance of major psychedelics for the future of sentience. But it’s also hard to convey why these agents can be valuable tools of investigation to academics who have never tried them. I know distinguished drug-naive philosophers of mind (and transhumanists) who are certain that psychedelia can’t be significant – and it would be irresponsible to urge them to put their assumptions to the test. Perhaps the best I can do is offer an analogy. Imagine an ultra-intelligent tribe of congenitally blind extraterrestrials. Their ignorance of vision and visual concepts is not explicitly represented in their conceptual scheme. To members of this hypothetical species, visual experiences wouldn’t be information-bearing any more than a chaotic drug-induced eruption of bat-like echolocatory experiences would be information-bearing to us. Such modes of experience have never been recruited to play a sensory or signaling function. At any rate, some time during the history of this imaginary species, one of the tribe discovers a drug that alters his neurochemistry. The drug doesn’t just distort his normal senses and sense of self. It triggers what we would call visual experiences: vivid, chaotic in texture and weirder than anything the drug-taker had ever imagined. What can the drug-intoxicated subject do to communicate his disturbing new categories of experiences to his tribe’s scientific elite? If he simply says that the experiences are “ineffable”, then the sceptics will scorn such mysticism and obscurantism. If he speaks metaphorically, and expresses himself using words from the conceptual scheme grounded in the dominant sensory modality of his species, then he’ll probably babble delirious nonsense. Perhaps he’ll start talking about messages from the gods or whatever. Critically, the drug user lacks the necessary primitive terms to communicate his experiences, let alone a theoretical understanding of what’s happening. Perhaps he can attempt to construct a rudimentary private language. Yet its terms lack public “criteria of use”, so his tribe’s quasi-Wittgensteinian philosophers will invoke the (Anti-)Private Language Argument to explain why it’s meaningless. Understandably, the knowledge elite are unimpressed by the drug-disturbed user’s claims of making a profound discovery. They can exhaustively model the behaviour of the stuff of the physical world with the equations of their scientific theories, and their formal models of mind are computationally adequate. The drug taker sounds psychotic. Yet from our perspective, we can say the alien psychonaut has indeed stumbled on a profound discovery, even though he has scarcely glimpsed its implications: the raw materials of what we would call the visual world in all its glory.

 

Anyhow, I worry that our own predicament resembles in more extreme form the hubris of the blind super-rationalists I describe above. In fact, intellectually, I worry far more about my ignorance of other modes of conscious existence than I do my cognitive biases or deficiencies of reasoning within ordinary waking consciousness. Sure, I’d love to know the master equation of a unified field theory. I’d love even more to know what it’s like to inhabit a world of echolocation like a bat – and to understand the indescribable weirdness of LSD, DMT or Salvia. It transpires that ordinary waking and dreaming consciousness are just two among numerous wholly or partially incommensurable realms of sentience. What we call waking consciousness was doubtless a fitness-enhancing adaptation in the ancestral environment of adaptation. But it occupies only a tiny fraction of experiential state-space. Our ignorance is all the more insidious because it is not explicitly represented in our conceptual scheme. From the inside, a dreamer has little insight into the nature of a dream, even in rare moments of “lucid dreaming”; and I fear this may be true of ordinary waking consciousness too. Unfortunately, the only way to even partially apprehend the nature of radically altered states is by first-person investigation, i.e. to instantiate the neurochemical substrates of the states in question. If drug-naive, you can’t fruitfully read about them. Compare how (ostensibly) trivial is the difference in the gene expression signature of neurons mediating phenomenal colour and sound. Who knows what further categories of experience other “trivial” bimolecular variations will open up, not to speak of more radical neurochemical changes? Thousands of scholarly philosophy papers and books have been written on consciousness in recent years by drug-naive academics. Psychedelic researchers worry that too many of them evoke Aristotelean scholasticism, whereas what we need is a post-Galilean experimental science of consciousness. Perhaps the nearest I come to an intellectual hero is psychedelic chemist Alexander Shulgin, whose pioneering methodology is described in PiHKAL. Alas, Shulgin doesn’t yet occupy a prominent place in the transhumanist pantheon.

 

It’s worth stressing that taking psychedelics is not a fast-track passport to either happiness or wisdom. If you take the kappa opioid agonist Salvinorin A found in Salvia divinorum, for instance, you might easily have a waking nightmare. And the experience may easily be unintelligible rather than illuminating. Even in a society of sighted people and a rich visually-based conceptual scheme, it takes years for a congenitally blind person who is surgically granted the gift of sight to master visual literacy. So understanding the implications of radically altered states may well take millennia. I’d hazard a guess and say comprehension will take millions of years and more. Either way, our descendants may be not just superintelligent but supersentient – blessed with the capacity to shift between a multitude of radically different modes of consciousness whose only common ingredient is the molecular signature of bliss. Posthuman mastery of reward circuitry will let them safely explore psychedelia in a way most humans beings don’t dare. Yes, it’s prudent for us to play safe; but in consequence our consciousness may be comparatively shallow and one-dimensional. Mine is today.

 
David Pearce‘s response to a question during an H+ interview (Autumn 2009)

GHB vs. MDMA

A brief comparison of GHB and MDMA may be instructive because one therapeutic challenge ahead will be to design agents that reverse SSRI-like flattening of affect without inducing mawkish sentimentalism (cf. ethyl alcohol). In contrast to mainstream psychiatric drug therapies, both GHB and MDMA deliver a rare emotional intensity of experience, albeit an intensity different both in texture and molecular mechanism. GHB is known by clubbers if not structural chemists as “liquid ecstasy”. GHB and MDMA are indeed sometimes mixed at raves; but the two drugs are chemically unrelated. GHB is an endogenous neuromodulator derived from GABA, the main inhibitory neurotransmitter of the brain. A naturally-occurring fatty acid derivative, GHB is a metabolite of normal human metabolism. GHB has its own G protein-coupled presynaptic receptor in the brain. Sold as a medicine, GHB is licensed as an oral solution under the brand name Xyrem for the treatment of cataplexy associated with narcolepsy. Unlike MDMA, GHB stimulates tissue serotonin turnover. GHB increases both the transport of tryptophan to the brain and its uptake by serotonergic cells. Taking GHB stimulates growth hormone secretion; hence its popularity with bodybuilders. GHB offers cellular protection against cerebral hypoxia, and deep sleep without inducing a hangover. GHB also stimulates tyrosine hydroxylase. Tyrosine hydroxylase converts L-tyrosine to L-dopa, subsequently metabolised to dopamine. Unlike MDMA, the acute effects of GHB involve first inhibiting the dopamine system, followed the next day by a refreshing dopamine rebound. GHB induces mild euphoria in many users. In general, the neurotransmitter GABA acts to reduce the firing of the dopaminergic neurons in the tegmentum and substantia nigra. The sedative/hypnotic effect of GHB is mediated by its stimulation of GABA(B) receptors, though GHB also modulates the GABA(A) receptor complex too. The main effect of GABA(B) agonism is normally muscle relaxation, though interestingly, pretreatment with the GABA(B) agonist baclofen also prevents an MDMA-induced rise in core body temperature. Whatever the exact GABA(A), GABA(B), and GHB-specific mechanisms by which GHB works, when taken at optimal dosage GHB typically acts as a “sociabiliser”. This is a term popularised by the late Claude Rifat (Claude de Contrecoeur), author of GHB: The First Authentic Antidepressant (1999). Rifat was GHB’s most celebrated advocate and an outspoken critic of Anglo-American psychiatry. Similar therapeutic claims have been made for GHB as for MDMA, despite their pharmacological differences. GHB swiftly banishes depression and replaces low mood with an exhilarating feeling of joy; GHB has anxiolytic properties; it’s useful against panic attacks; it suppresses suicidal ideation; it inhibits hostility, paranoia and aggression; it enhances the recall of long-forgotten memories and dreams; and it promotes enhanced feelings of love. Like MDMA, and on slightly firmer grounds, GHB has been touted as an aphrodisiac: GHB heightens and prolongs the experience of orgasm. GHB disinhibits the user, and deeply relaxes his or her body. Inevitably, GHB has been demonised as a date-rape drug [“I was at this party, and this guy gave me a drink. Next thing I know, it’s morning and I’m in someone’s bed. I’ve no idea what happened in between…”]. GHB has a steep dose-response curve. Higher doses will cause anterograde amnesia i.e. users forget what they did under the influence of the drug. It’s dangerous to combine GHB with other depressants. So despite GHB’s therapeutic and pro-social potential, GHB is probably unsafe to commend to clubbers. This is because a significant percentage of the population will combine any drug whatsoever with alcohol regardless of the consequences to health. If used wisely, sparingly, and in a different cultural milieu, then GHB could be a valuable addition to the bathroom pharmacopoeia. But even then, it’s still flawed. GHB may intensify emotion and affection, but not introspective depth or intellectual acuity. Unlike taking too much MDMA, overdoing GHB makes the user fall profoundly asleep. If our consciousness is to be durably enhanced, then sedative-hypnotics have only a limited role to play in the transition ahead.

– Extract from “Utopian Pharmacology: Mental Health in the Third Millennium
MDMA and Beyond” by David Pearce (notice the great domain name: mdma.net)

Hedonium

Desiring that the universe be turned into Hedonium is the straightforward implication of realizing that everything wants to become music.

The problem is… the world-simulations instantiated by our brains are really good at hiding from us the what-it-is-likeness of peak experiences. Like Buddhist enlightenment, language can only serve as a pointer to the real deal. So how do we use it to point to Hedonium? Here is a list of experiences, concepts and dynamics that (personally) give me at least a sort of intuition pump for what Hedonium might be like. Just remember that it is way beyond any of this:

Positive-sum games, rainbow light, a lover’s everlasting promise of loyalty, hyperbolic harmonics, non-epiphenomenal bliss, life as a game, fractals, children’s laughter, dreamless sleep, the enlightenment of emptiness, loving-kindness directed towards all sentient beings of past, present, and future, temperate wind caressing branches and leaves of trees in a rainforest, perfectly round spheres, visions of a giant ying-yang representing the cosmic balance of energies, Ricci flowtranspersonal experiences, hugging a friend on MDMA, believing in a loving God, paraconsistent logic-transcending Nirvana, the silent conspiracy of essences, eating a meal with every flavor and aroma found in the quantum state-space of qualia, Enya (Caribbean Blue, Orinoco Flow), seeing all the grains of sand in the world at once, funny jokes made of jokes made of jokes made of jokes…, LSD on the beach, becoming lighter-than-air and flying like a balloon, topological non-orientable chocolate-filled cookies, invisible vibrations of love, the source of all existence infinitely reflecting itself in the mirror of self-awareness, super-symmetric experiences, Whitney bottles, Jhana bliss, existential wonder, fully grasping a texture, proving Fermat’s Last theorem, knowing why there is something rather than nothing, having a benevolent social super-intelligence as a friend, a birthday party with all your dead friends, knowing that your family wants the best for you, a vegan Christmas eve, petting your loving dog, the magic you believed in as a kid, being thanked for saving the life of a stranger, Effective Altruism, crying over the beauty and innocence of pandas, letting your parents know that you love them, learning about plant biology, tracing Fibonacci spirals, comprehending cross-validation (the statistical technique that makes statistics worth learning), reading The Hedonistic Imperative by David Pearce, finding someone who can truly understand you, realizing you can give up your addictions, being set free from prison, Time Crystals, figuring out Open Individualism, G/P-spot orgasm, the qualia of existential purpose and meaning, inventing a graph clustering algorithm, rapture, obtaining a new sense, learning to program in Python, empty space without limit extending in all directions, self-aware nothingness, living in the present moment, non-geometric paradoxical universes, impossible colors, the mantra of Avalokiteshvara, clarity of mind, being satisfied with merely being, experiencing vibrating space groups in one’s visual field, toroidal harmonics, Gabriel’s Oboe by Ennio Morricone, having a traditional dinner prepared by your loving grandmother, thinking about existence at its very core: being as apart from essence and presence, interpreting pop songs by replacing the “you” with an Open Individualist eternal self, finding the perfect middle point between female and male energies in a cosmic orgasm of selfless love, and so on.