Psychoactive Anecdata

[Epistemic Status: anecdotal data; this is not a list of “life hacks”; it is intended as a list of interesting research leads; don’t take drugs unless you really know what you are doing!]

I’ll mark to the right of each anecdata:

  • n=x when I can remember clearly how many people have said this to me up to n = 10 (e.g. n=7 means that 7 people have told me this)
  • n=x/y when I know that y people have tried it and of those x have experienced this
  • n>1 when 1 < n < 10 but I don’t remember exactly how many people have said it, and
  • pattern if it’s a pattern I’ve observed across more than 10 people pooled from online trip reports and conversations from email exchanges, forums, group chats, private messages, and things that have come up at IRL discussions (e.g. at festivals).

Psychedelics

The “best” phenethylamines in terms of the balance between mind expansion, euphoria, and low bodyload are:

  • 2C-B (low bodyload, high euphoria, unlikely to freak out at <25mg) [pattern]
  • 2C-C (like 2C-B but also relaxing, unlikely to freak out at <40mg) [pattern]
  • 2C-D (particularly easy on the body relative to other phenethylamines, unlikely to freak out at <30mg) [pattern]
  • 2C-I (more trippy and stimulating than the above, unlikely to freak out at <25mg) [pattern]

Among some of the worst 2Cs (but perhaps not worst phenethylamines) we find:

  • 2C-P (particularly bad bodyload, inevitable vomiting above some dose) [pattern]
  • 2C-E (“just too weird” for a lot of people, strong bodyload) [pattern]
  • 2C-T-2 (high bodyload, strangely similar to LSD in headspace) [n>1]
  • 2C-T-7 (same as 2C-T-2) [n>1]

IV Psychedelics

  • Do not ever IV 2C-E as it leads to instant extreme crams, nausea, and general bodily discomfort. [n=1]
  • The come-up of IV 2C-B is very fast relative to oral administration (5 minutes) and the peak is a lot more intense as well. 5mg results in an intensity of experience comparable to 35mg oral at its peak. [n=5]
  • Within 10 minutes of IV 2C-B one feels an intense urge to defecate. [n=4/5]
  • While IV 100μg LSD takes a full 30 minutes to show the start of effects, IV 300μg takes only 5 minutes to show pronounced effects. [n=1]
  • Ketamine is reportedly experienced as a “completely different drug” when the ROA is IV vs. IM vs. intranasal. [pattern]
  • IV Ketamine gives rise to a distinct metallic taste in one’s mouth within a few seconds of administration. [n>1]

Anti-Tolerance Drugs

In Anti-Tolerance Drugs we gave a list of drugs that, when taken in conjunction with painkillers and euphoric substances, can lessen, prevent, and even reverse tolerance. But “drug tolerance” is not a natural kind. Indeed, there are many systems of neuroadaptation that prevent drugs from exerting the same effect over time. Nothing makes this clearer than the typically life-long loss of “magic” to MDMA after a few experiences, which stands in contrast to the largely reversible tolerance to ethyl alcohol post-PAWS. Indeed, “drug tolerance” can mean tolerance to reduced action for: antidepressant effects (SSRIs), lessening chronic pain (opioids), increasing executive function (modafinil), enhancing motivation (amphetamine), “the magic” (ketamine, MDMA), the sense of unity and interconnectedness (LSD), otherworldliness (salvia), and so on. Indeed you can have a drug that generates tolerance to one of its effects but not others. For example, Slate Star Codex’s nootropic survey found that despite the common wisdom that prescription amphetamines stop generating a sense of euphoria after a while, most people who use them clinically for ADHD continue to experience an enhanced focus on the drug for many years. In this vein, the following anecdata highlights how anti-tolerance drugs have a much more subtle and multifaceted effect than just “reducing tolerance”:

  • DXM and other dissociatives seem to potentiate both the analgesic and euphoric effects from opioids, increase constipation, and leave pruritus the same. [n>1]
  • Proglumide reduces both the intensity of opioid withdrawal as well as the tolerance to their analgesic, sedative, and constipation effects. It does not affect euphoria or pruritus. [n>1]
  • Ultra-low dose naltrexone (ULDN) reduces tolerance to analgesic and sedative effects from opioids but not euphoria (“it makes opioids more sleep-inducing but a lot less fun“). Interestingly, ULDN prevents constipation from opioids. [n>1]
  • Black seed oil and ashwagandha reduce the tolerance to the analgesic, sedative, euphoric, and pruritus effects of opioids without influencing constipation. These effects are milder than all of the above. [n=1]
  • Agmatine potentiates the analgesic effects of opioids without an effect on other facets like euphoria or constipation. [n =1]
  • Turmeric primarily increases the sedative effects of opioids without changing much of anything else. [n=1]
  • Anti-histamine anti-cholinergic drugs (such as diphenhydramine) potentiate the sedative and analgesic effects, but leave constipation and euphoria the same. They can increase restlessness. [pattern]

Drug Combinations

In addition to all of what was said in Making Amazing Recreational Drug Cocktails:

  • DXM does not mix well with a bunch of things: 2C drugs [n>1], noopept [n=1], tianeptine [n=1], phenibut [n=1], ethyl alcohol [pattern], most nootropics. [n=1]
    • This seems to be especially bad for high-bodyload 2Cs as described above. [n>1]
  • Vaporizing DMT while on ketamine “slows down” and in some cases “freezes” some aspects of the hallucinations of DMT, allowing you to inspect them more closely. It also prolongs the DMT experience for a good 3 to 5 minutes. [n=3]
  • Taking 30mg of MDMA and 30μg LSD at the same time, followed by 10mg 2C-B four hours later, gives rise to a very positive synergy that allows you to maintain easy executive function while having trippy thoughts and a very high hedonic tone. It’s a smart and psychologically safe state. The combo has very mild hungover effects relative to how great it feels. [n=4]

Nootropics

  • Coluracetam is surprisingly psychedelic. [n=5]
  • Mixing coluracetam and weed gives rise to a mild LSD-like mindspace. [n=4]
  • Rhodiola Rosea has a distinctly “dopaminergic quality”, which is rare among nootropics other than L-tyrosine. [n=3]
  • Most racetams (piracetam, oxiracetam, aniracetam, etc.) successfully mask the verbal impairment (both comprehension and execution) caused by weed and/or alcohol (up to a point!). [pattern]
  • Agmatine (500mg) significantly blunts the intensity of orgasm. [n=1]
  • Agmatine (500mg) can be used as a replacement for NSAIDs like aspirin and ibuprofen for mild to moderate pains and aches. [n=1]

Surprising Analgesia

  • Microdosing LSD (5 to 20μg) can substantially reduce the pain of very bad premenstrual syndrome (PMS). [pattern]
  • Microdosing LSD can also reduce the pain associated with shingles. [1<n]

Spiral

[Excerpt from Phenethylamines I Have Known And Loved (published in 1990 and usually abbreviated as PIHKAL) by Alexander and Ann Shulgin, pgs. 98-103]

Part Two: Alice’s Voice

Spiral

When I finally gave it a name, I called it the Spiral.

This is how it was. Lying down for a nap time (as a child) or at night for sleep, I would have reached that point of relaxation where one is not very much aware of the body. The small itches and discomforts have subsided, and the mind is beginning to drift. When I sensed it beginning (I never knew when it was going to come), I would immediately snap into alertness, excited and pleased, then I would just lie quietly as it unfolded.

The first thing that happened was a change in my breathing. It became increasingly shallow, to the point where my rib cage was barely moving at all.

If someone came into the room and talked to me, as sometimes happened, I could open my eyes and answer normally; the experience continued uninterrupted inside my head.

Every part of it, every stage, was the same each time. It was always in black and white. There was no color anywhere, and try as I did, especially around the age of fourteen, I could not force color to come onto the screen. And I could never extend it, by so much as a few seconds. When it was finished, it was finished.

First came the image-sensation after which I named the entire experience – the spiral. I felt my entire self drawn rapidly into a tiny point which kept shrinking, until it could shrink no further, at which time the microscopic point became a tunnel in which I continued traveling at great speed, inexpressibly small and implacably diminishing.

Simultaneously, I was expanding. I was expanding to the edges of the universe, at the same tremendous speed as that of the shrinking, and the combination, the contraction-expansion, was not only an image, it was also a sensation the whole of me recognized and welcomed. This experience of myself as microcosm-macrocosm lasted exactly four minutes.

The image of the spiral is found everywhere that the human has left his mark on earth. It has been cut into rock faces, painted on huts and clay pots, traced on the walls of initiation caves. I’m certain that it has been important to all the races of man because it is a symbol for the experience I’m describing, and for the concept, the understanding that the intellect forms out of what is initially not an intellectual, but a soul experience of the Alpha and the Omega.

The next stage came abruptly, as did all the changes. I was looking at standing figures which were vaguely human, dark thin figures being pulled into elongated shapes, like the sculptures of Giacometti. They stretched out, arms and legs like black string, until it seemed they could elongate no further, then the scene changed and I was watching obscenely rounded bodies, Tweedledums and Tweedledees without costumes, their small heads and legs disappearing into their puffed, bloated flesh.

The sensation accompanying this stage was one of discomfort, unpleasantness, a feeling of something grating on my soul. I once timed this part and the one that followed; they lasted a total of six minutes. I disliked them intensely.

Abruptly again, the inner screen became white, a horrible dead-white, nasty and aggressive like the underbelly of a sting-ray. After presenting itself for a few seconds, the flat white began to curdle from the outer edges into black, until finally the screen was totally black. A thick, awful, dead black, a pool of tar in an unlit cave deep underground. After another brief pause, the black began to curdle at its edges into the white again. The process repeated itself once, and the sensation was similar in every way to the previous one: irritating, grating, a feeling of unpleasantness that approached repugnance. I always endured it with a mental gritting of teeth, knowing it had to be gone through because that’s the way it always went and it was not to be changed.

And then, finally, I broke out into the last stage, the final part for which I had always been and always would be willing to undergo the middle parts.

Now I was at the edge of an unseen cliff, looking out into a very different blackness, the deep, cradling blackness of the infinite universe, of space which stretched without end. I was completely happy and comfortable in that place, and would have stayed there indefinitely, had I been allowed, breathing in the beautiful darkness and the exquisitely familiar sense of infinity as a living presence, surrounding me, intimate and warm.

After a moment of this pleasure, came the greeting. From the upper left-hand corner of the universe there came a greeting from Something which had known me, and which I had known, since before time and space began. There were no words, but the message was clear and smiling: Hello, dear friend, I salute you with respect-humor-love. It is a pleasure with laughter-joy to encounter you again.

That which greeted me was an entity so far removed from anything in human experience that I concluded, when I was an adult, trying to find a way to describe it to myself, that even the word, “entity”, could not be applied; a word creates boundaries, it says this is the shape of what you are describing, as different from other shapes which are bounded by other words. It had no shape, no form, no definition, no boundaries. It was. It is. It was my oldest friend and it greeted me as its equal. I always replied to it with a rush of love and delight and my own laughter.

Then it was over.

It had taken exactly twelve minutes.

It was something I’d always experienced, taken for granted, and had given no thought to when I was very young. Not until age fourteen did I take a good look at it and recognize it as unusual, something peculiarly my own, my secret private treasure. I also got very analytical about the whole thing, began my habit of timing it and made the first of my unsuccessful efforts at altering it. But I didn’t decide on a name for it until many years later, discarding “Microcosm-macrocosm,” as too long and unwieldy, and settling on the simpler “Spiral.”

It had probably been going on since I was born. There’s no way to be sure, of course, but because it had been part of my life ever since I could remember, I tend to assume it was familiar to me from the very beginning. My mother said something once about having seen a change of some kind coming over me occasionally when I was a baby; she said she didn’t worry about it because when it passed, I appeared to be quite normal.

It always (with one single exception) came under the same circumstances, when I had settled down in bed for a nap or for the night’s sleep, but well before sleep itself took over.

The one exception happened when I was around fifteen, shortly after my father had been transferred to Santiago de Cuba as American Consul. We were staying in a hotel, while those responsible for helping us find a home were still busy with their search. My father and mother, my brother Boy and I were having lunch in the hotel dinning room and my eyes focused on the butter plate on the table. In the exact center of the round plate was a single pat of butter, and somehow the sight triggered the familiar feeling I associated with the beginning of the Spiral. I was surprised and very pleased, because it was a new thing to have it start under such unusual circumstances.

I was also pleased because it was my special thing, and in asking to be excused from the table to go up to my room, I felt a certain sense of importance, which was rare when I was with my family. I said just enough to make it clear that my strange “thing” was beginning, and my parents grudgingly gave me permission for me to leave. I reached the room upstairs in time for the completion, the wonderful last few moments. It turned out to be the only time it ever happened that way – when I was out of my bed, involved with ordinary matters of daily living.

I tried to make it come, searching out all sorts of images of round space with dots in the center, but nothing worked. I never found a way to make it happen. It came when it chose to, unexpectedly, once in a while. The times it chose had no apparent connection to anything else that was going on in my life, either generally or in particular. In twenty-five years, believe me, I looked for every possible connection; I found none. When I was very little, I think it might have happened as often as once a week or so, but as I grew older it came less and less often, until around age twenty-five, when it happened only twice in one year, then never again.

The discovery that I was not alone in my journey into the interior cosmos came as a complete surprise. It gave me a great deal of excited pleasure and opened up a whole new series of questions. I happened when I was around twenty two, and – interesting enough in itself – the two proofs came to me within a single four month period.

The incidents were astoundingly similar.

The first one took place one evening when I went to a party given by a friend in San Francisco. I was in the host’s kitchen with several of the other guests, doing what people usually do in strange kitchens at informal parties – talking, drinking and munching potato chips and carrot sticks – and after a while one young man named Evan and I found ourselves alone, deeply involved in a conversation about unusual experiences, mostly read about or heard from others, the kind of conversation that seems to come about more easily, somehow, in the midst of a high energy, noisy party than at any other time.

Suddenly Evan was telling me about what he referred to as “a really weird thing,” which had been happening to him ever since he was very young. I remember the prickling that spread up my back as he began describing it, and I understood immediately the look that gradually came into his face, a mixture of embarrassment and anxiety (She’s going to think I’m crazy; why am I talking about this?). I tried to make it easier for him to continue by nodding encouragingly and once – when he faltered briefly – I volunteered what I knew was going to be the next image, and he looked startled, almost frightened, drank a bit from his glass, muttered, “Yes, exactly”, and continued to the end. His end was not mine; his journey came to a close after the black and white curdles. I thought, with a touch of pity, that he seemed to have missed the best part, although he did have the wonderful spiral at the beginning. I was glad I hadn’t prompted him further. When he’d finished his story, I told him I’d had every one of the images he had described, and that he was the first person I’d ever met who shared the experience. I said nothing about my own different ending.

He was staring at me, and I wasn’t sure he’d really heard what I’d been telling him. Finally, he smiled and said that I was the first person he’d ever told about this private, “crazy thing,” and he couldn’t believe – it was so extraordinary – that I actually knew what he was talking about. He said that he had always wondered if the experience was a sign of insanity of some kind, and it was such a relief to know that somebody else had had it. Neither of us felt it necessary to add that, in a situation like this, it was also reassuring to see that the person who shares your strangeness appears to be relatively sane and reasonably functional.

I smiled back and said I understood exactly how he felt. We left the kitchen and joined the rest of the party. I never saw him again, and didn’t particularly expect or want to. It was enough to have heard one other person repeating what I knew so well, and it was intriguing to know that my journey, or process, had gone farther, longer, than Evan’s; after all, although I was more than willing to give up exclusive rights to the whole thing, I didn’t mind retaining a little bit of superiority.

The second incident was almost identical to the first, the only difference being that the young man (whose name I forgot almost immediately) was talking to me in somebody’s living room, instead of the kitchen, in the middle of another noisy party, when he began describing the “strange vision” that he, too, had had ever since he was a small child. His, also, ended short of where mine did, and he was astounded and obviously very relieved to know that there was somebody else in the world who knew about it.

Both young men seemed quite unremarkable, although pleasant enough and intelligent. I never saw the second one again, either.

I remember wishing briefly that I could put an ad in the Chronicle or Examiner, something along the lines of, “Seek contact with others who have experienced…,” and of course, the imaginary ad stalled there.

It happened – my beloved Spiral – for the last time when I was twenty-five. I had no way of knowing, of course, that it would not come again. It may or may not have been a coincidence that, within three weeks of the last time, I had my first encounter with a psychedelic material, the Divine Cactus, peyote.



Has the above ever happened to you? Did you experience the Spiral as a kid? If so, please let us know!

See also:


Featured Image Credit: Matthew Smith

That Time Daniel Dennett Took 200 Micrograms of LSD (In Another Timeline)

[Epistemic status: fiction]

Andrew Zuckerman messaged me:

Daniel Dennett admits that he has never used psychedelics! What percentage of functionalists are psychedelic-naïve? What percentage of qualia formalists are psychedelic-naïve? In this 2019 quote, he talks about his drug experience and also alludes to meme hazards (though he may not use that term!):

Yes, you put it well. It’s risky to subject your brain and body to unusual substances and stimuli, but any new challenge may prove very enlightening–and possibly therapeutic. There is only a difference in degree between being bumped from depression by a gorgeous summer day and being cured of depression by ingesting a drug of one sort or another. I expect we’ll learn a great deal in the near future about the modulating power of psychedelics. I also expect that we’ll have some scientific martyrs along the way–people who bravely but rashly do things to themselves that disable their minds in very unfortunate ways. I know of a few such cases, and these have made me quite cautious about self-experimentation, since I’m quite content with the mind I have–though I wish I were a better mathematician. Aside from alcohol, caffeine, nicotine and cannabis (which has little effect on me, so I don’t bother with it), I have avoided the mind-changing options. No LSD, no psilocybin or mescaline, though I’ve often been offered them, and none of the “hard” drugs.

 

As a philosopher, I have always accepted the possibility that the Athenians were right: Socrates was quite capable of corrupting the minds of those with whom he had dialogue. I don’t think he did any clear lasting harm, but it is certainly possible for a philosopher to seriously confuse an interlocutor or reader—to the point of mental illness or suicide, or other destructive behavior. Ideas can be just as dangerous as drugs.

 

Dennett Explained by Brendan Fleig-Goldstein and Daniel A. Friedman (2019)


It would be quite fascinating to know what Dan would say about lived psychedelic states. With that in mind, here is an essay prompt originally conceived for GPT-3 to satisfy our curiosity:

And after seeing some surprising empirical results with his heterophenomenological methods when examining the experience of people on psychedelics, Daniel Dennett decided to experience it for himself by taking 200 micrograms of LSD. The first thing he said to himself as he felt the first indications of the come-up was…


anders_and_maggie

Maggie and Anders

Maggie Wassinge and Anders Amelin (QRI Sweden volunteer coordinators and content contributors – see letters I & II, letters III, IV, V, & VI, and letters VII, VIII, & IX) decided to give it a go first. We shall then compare it with what GPT-3 can come up with at a later point.

In a way, what you are about to read can be thought of as Anders & Maggie’s simulation of a hyper-intelligent GPT-3-like system’s simulation of a hypothetical Daniel Dennett on LSD. So many layers, I know. But the results speak for themselves:


Dan says: Correlation is all that is needed. So what states a mind uses for modeling conditions of importance to it, is fundamentally arbitrary. Like with language. Words represent things to humans but there are many languages, and words do not resemble what they represent. They only correlate with what they represent, and the correlation needs to be learned. To do science about the mind, one does not need to attach any special weight to any conscious state of mind over any other. One person’s hope may be another person’s despair. These “qualia” are like internally projected hypo-languages which are different all over the map, if there were one. In fact there cannot be an interpersonal map of what things feel like personally. Only naïve people could hope for a fundamental linguistics of consciousness, as if these states were to constitute a universal language of some ground truth of the mind. Silly. Romantic. It’s all arbitrary. For the record, I never said subjective experiential states do not exist. People misrepresent me on that. What I am saying is that it will never be possible to scientifically map what the state that a word such as, for instance, “green”, translates to feels like by the brain of a given individual. My green could be your red.cielab-lch-color-tolerancing-methods

Just drop the whole idea of trying to map the state-space of qualia. That is my position. Or at least I know it is, logically. Right now I begin to notice how everything intensifies and becomes somehow more salient. More revealingly “real”. As I reflect on the notion of how “states” correlate, a humorous episode from my undergraduate student life so long ago, is brought to the surface. At Wesleyan it was, where I was taking a course in Art Appreciation. The lecturer was showing a slide of a still life. A bowl of fruit it was, conspicuously over-ripe. Pointing at one of the fruits, saying “Can anyone tell me what state this peach is in?” There was silence for about three seconds, then one student exclaimed: “Georgia”. Everyone laughed joyfully. Except me. I never quite liked puns. Too plebeian. Sense of humor is arbitrary. I believe that episode helped convince me that the mind is not mysterious after all. It is just a form of evolved spaghetti code finding arbitrary solutions to common problems. Much like adaptations of biochemistry in various species of life. The basic building blocks remain fixed as an operative system if you will, but what is constructed with it is arbitrary and only shaped by fitness proxies. Which are, again, nothing but correlations. I realized then that I’d be able to explain consciousness within a materialist paradigm without any mention of spirituality or new realms of physics. All talk of such is nonsense.Daniel_dennett_Oct2008

I have to say, however, that a remarkable transformation inside my mind is taking place as a result of this drug. I notice the way I now find puns quite funny. Fascinating. I also reflect on the fact that I find it fascinating that I find puns funny. It’s as if… I hesitate to think it even to myself, but there seems to be some extraordinarily strong illusion that “funny” and “fascinating” are in fact those very qualia states which… which cannot possibly be arbitrary. Although the reality of it has got to be that when I feel funniness or fascination, those are brain activity patterns unique to myself, not possible for me to relate to any other creature in the universe experiencing them the same way, or at least not to any non-human species. Not a single one would feel the same, I’m sure. Consider a raven, for example. It’s a bird that behaves socially intricately, makes plans for the next day, can grasp how tools are used, and excels at many other mental tasks even sometimes surpassing a chimpanzee. Yet a raven has a last common ancestor with humans more than three hundred million years ago. The separate genetic happenstances of evolution since then, coupled with the miniaturization pressure due to weight limitations on a flying creature, means that if I were to dissect and anatomically compare the brain of a raven and a human, I’d be at a total loss. Does the bird even have a cerebral cortex?03-brai-diagram

An out of character thing is happening to me. I begin to feel as if it were in fact likely that a raven does sense conscious states of “funny” and “fascinating”. I still have functioning logic that tells me it must be impossible. Certainly, it’s an intelligent creature. A raven is conscious, probably. Maybe the drug makes me exaggerate even that, but it ought to have a high likelihood of being the case. But the states of experience in a raven’s mind must be totally alien if it were possible to compare them side by side with those of a human, which of course it is not. The bird might as well come from another planet.Head_of_Raven

The psychedelic drug is having an emotional effect on me. It does not twist my logic, though. This makes for internal conflict. Oppositional suggestions spontaneously present themselves. Could there be at least some qualia properties which are universal? Or is every aspect arbitrary? If the states of the subjective are not epiphenomenal, there would be evolutionary selection pressures shaping them. Logically there should be differences in computational efficiency when the information encoded in qualia feeds back into actions carried out by the body that the mind controls. Or is it epiphenomenal after all? Well, there’s the hard problem. No use pondering that. It’s a drug effect. It’ll wear off. Funny thing though, I feel very, very happy. I’m wondering about valence. It now appeals strongly to take the cognitive leap that at least the positive/negative “axis” of experience may in fact be universal. A modifier of all conscious states, a kind of transform function. Even alien states could then have a “good or bad” quality to them. Not directly related to the cognitive power of intelligences, but used as an efficient guidance for agency by them all, from the humblest mite to the wisest philosopher. Nah. Romanticizing. Anthropomorphizing.

36766208_10160731731785637_6606215010454601728_oFurther into this “trip” now. Enjoying the ride. It’s not going to change my psyche permanently, so why not relax and let go? What if conscious mind states really do have different computational efficiency for various purposes? That would mean there is “ground truth” to be found about consciousness. But how does nature enable the process for “hitting” the efficient states? If that has been convergently perfected by evolution, conscious experience may be more universal than I used to take for granted. Without there being anything supernatural about it. Suppose the possibility space of all conscious states is very large, so that within it there is an ideally suited state for any mental task. No divine providence or intelligent design, just a law of large numbers.

The problem then is only a search algorithmic one, really. Suppose “fright” is a state ideally suited for avoiding danger. At least now, under the influence, fright strikes me as rather better for the purpose than attraction. Come to think of it, Toxoplasma Gondii has the ability to replace fright with attraction in mice with respect to cats. It works the same way in other mammals, too. Are things then not so arbitrarily organized in brains? Well, those are such basic states we’d share them with rodents presumably. Still can’t tell if fright feels like fear in a raven or octopus. But can it feel like attraction? Hmmm, these are just mind wanderings I go through while I wait for this drug to wear off. What’s the harm in it?

Suppose there is a most computationally efficient conscious state for a given mental task. I’d call that state the ground state of conscious intelligence with respect to that task. I’m thinking of it like mental physical chemistry. In that framework, a psychedelic drug would bring a mind to excited states. Those are states the mind has not practiced using for tasks it has learned to do before. The excited states can then be perceived as useless, for they perform worse at tasks one has previously become competent at while sober. Psychedelic states are excited with respect to previous mental tasks, but they would potentially be ground states for new tasks! It’s probably not initially evident exactly what those tasks are, but the great potential to in fact become more mentally able would be apparent to those who use psychedelics. Right now this stands out to me as absolutely crisp, clear and evident. And the sheer realness of the realization is earth-shaking. Too bad my career could not be improved by any new mental abilities.Touched_by_His_Noodly_Appendage_HD

Oh Spaghetti Monster, I’m really high now. I feel like the sober me is just so dull. Illusion, of course, but a wonderful one I’ll have to admit. My mind is taking off from the heavy drudgery of Earth and reaching into the heavens on the wings of Odin’s ravens, eternally open to new insights about life, the universe and everything. Seeking forever the question to the answer. I myself am the answer. Forty-two. I was born in nineteen forty two. The darkest year in human history. The year when Adolf Hitler looked unstoppable at destroying all human value in the entire world. Then I came into existence, and things started to improve.

It just struck me that a bird is a good example of embodied intelligence. Sensory input to the brain can produce lasting changes in the neural connectivity and so on, resulting in a saved mental map of that which precipitated the sensory input. Now, a bird has the advantage of flight. It can view things from the ground and from successively higher altitudes and remember the appearance of things on all these different scales. Plus it can move sideways large distances and find systematic changes over scales of horizontal navigation. Entire continents can be included in a bird’s area of potential interest. Continents and seasons. I’m curious if engineers will someday be able to copy the ability of birds into a flying robot. Maximizing computational efficiency. Human-level artificial intelligence I’m quite doubtful of, but maybe bird brains are within reach, though quite a challenge, too.

This GPT-3 system by OpenAI is pretty good for throwing up somewhat plausible suggestions for what someone might say in certain situations. Impressive for a purely lexical information processing system. It can be trained on pretty much any language. I wonder if it could become useful for formalizing those qualia ground states? The system itself is not an intelligence in the agency sense but it is a good predictor of states. Suppose it can model the way the mind of the bird cycles through all those mental maps the bird brain has in memory. Where the zooming in and out on different scales brings out different visual patterns. If aspects of patterns from one zoom level is combined with aspect from another zoom level, the result can be a smart conclusion about where and when to set off in what direction and with what aim. Then there can be combinations also with horizontally displaced maps and time-displaced maps. Essentially, to a computer scientist we are talking massively parallel processing through cycles of information compression and expansion with successive approximation combinations of pattern pieces from the various levels in rapid repetition until something leads to an action which becomes rewarded via a utility function maximization.

Integrated_information_theory_postulates

Axioms of Integrated Information Theory (IIT)

Thank goodness I’m keeping all this drugged handwaving to myself and not sharing it in the form of any trip report. I have a reputation for being down to Earth, and I wouldn’t want to spoil it. Flying with ravens, dear me. Privately it is quite fun right now, though. That cycling of mental maps, could it be compatible with the Integrated Information Theory? I don’t think Tononi’s people have gone into how an intelligent system would search qualia state-space and how it would find the task-specific ground states via successive approximations. Rapidly iterated cycling would bring in a dynamic aspect they haven’t gotten to, perhaps. I realize I haven’t read the latest from them. Was always a bit skeptical of the unwieldy mathematics they use. Back of the envelope here… if you replace the clunky “integration” with resonance, maybe there’s a continuum of amplitudes of consciousness intensity? Possibly with a threshold corresponding to IIT’s nonconscious feed-forward causation chains. The only thing straight from physics which would allow this, as far as I can tell from the basic mathematics of it, would be wave interference dynamics. If so, what property might valence correspond to? Indeed, be mappable to? For conscious minds, experiential valence is the closest one gets to updating on a utility function. Waves can interfere constructively and destructively. That gives us frequency-variable amplitude combinations, likely isomorphic with the experienced phenomenology and intensity of conscious states. Such as the enormous “realness” and “fantastic truth” I am now immersed in. Not sure if it’s even “I”. There is ego dissolution. It’s more like a free-floating cosmic revelation. Spectacular must be the mental task for which this state is the ground state!

Wave pattern variability is clearly not a bottleneck. Plotting graphs of frequencies and amplitudes for even simple interference patterns shows there’s a near-infinite space of distinct potential patterns to pick from. The operative system, that is evolution and development of nervous systems, must have been slow going to optimize by evolution via genetic selection early on in the history of life, but then it could go faster and faster. Let me see, humans acquired a huge redundancy of neocortex of the same type as animals use for avigation in spacetime locations. Hmmm…, that which the birds are so good at. Wonder if the same functionality in ravens also got increased in volume beyond what is needed for navigation? Opening up the possibility of using the brain to also “navigate” in social relational space or tool function space. Literally, these are “spaces” in the brain’s mental models.2000px-Migrationroutes.svg

Natural selection of genetics cannot have found the ground states for all the multiple tasks a human with our general intelligence is able to take on. Extra brain tissue is one thing it could produce, but the way that tissue gets efficiently used must be trained during life. Since the computational efficiency of the human brain is assessed to be near the theoretical maximum for the raw processing power it has available, inefficient information-encoding states really aren’t very likely to make up any major portion of our mental activity. Now, that’s a really strong constraint on mechanisms of consciousness there. If you don’t believe it was all magically designed by God, you’d have to find a plausible parsimonious mechanism for how the optimization takes place.

If valence is in the system as a basic property, then what can it be if it’s not amplitude? For things to work optimally, valence should in fact be orthogonal to amplitude. Let me see… What has a natural tendency to persist in evolving systems of wave interference? Playing around with some programs on my computer now… well, appears it’s consonance which continues and dissonance which dissipates. And noise which neutralizes. Hey, that’s even simple to remember: consonance continues, dissonance dissipates, noise neutralizes. Goodness, I feel like a hippie. Beads and Roman sandals won’t be seen. In Muskogee, Oklahoma, USA. Soon I’ll become convinced love’s got some cosmic ground state function, and that the multiverse is mind-like. Maybe it’s all in the vibes, actually. Spaghetti Monster, how silly that sounds. And at the same time, how true!

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Artist: Matthew Smith

I’m now considering the brain to produce self-organizing ground state qualia selection via activity wave interference with dissonance gradient descent and consonance gradient ascent with ongoing information compression-expansion cycling and normalization via buildup of system fatigue. Wonder if it’s just me tripping, or if someone else might seriously be thinking along these lines. If so, what could make a catchy name for their model?

Maybe “Resonant State Selection Theory”? I only wish this could be true, for then it would be possible to unify empty individualism with open individualism in a framework of full empathic transparency. The major ground states for human intelligence could presumably be mapped pretty well with an impressive statistical analyzer like GPT-3. Mapping the universal ground truth of conscious intelligence, what a vision!

But, alas, the acid is beginning to wear off. Back to the good old opaque arbitrariness I’ve built my career on. No turning back now. I think it’s time for a cup of tea, and maybe a cracker to go with that.

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Self-Locatingly Uncertain Psilocybin Trip Report by an Anonymous Reader

See more rational trip reports by anonymous readers for: 2C-B, 4-AcO-DMT, LSD, N,N-DMT, 5-MeO-DMT


Pre-ingestion Notes

Physiological Background

  • Restfulness: Well-Rested (7-8 hours of sleep)
  • Wake-up time: 5:10 am
  • Morning run: 5:30 am (~30 minutes total)
  • Breakfast time: 9:25 am
  • Food: 2 chicken sausages + ½ bagel, ¾ can of Peach-Pear La Croix (carbonation will create a slightly acidic environment, possibly potentiating drug’s metabolism)
  • Weight: 55-60 kg
  • Height: 170-180 cm
  • Sex / Identity / Orientation: Male / Cis / Hetero
  • Libido: decently high; 2 days since last masturbation
  • Dosage: 6 g, mostly caps; took 2x dosage of everyone else to prevent any potential short-term homeostatic adaptive effects which might lead to upping dosage mid-stride
  • Other Drugs: none

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“I have a split personality”, said tom, being frank

Environmental Stimuli

  • Temperature: moderately warm – cozy (~ 74 F, 23 C)
  • Light: near window with ample filtered sunlight
  • Touch: sitting on fuzzy carpet; comfortable loose-fitting athleisure wear clothes
  • Olfactory: 5 sprays of peach-nectarine body scent (as an experiment to test memory retrieval of trip, as unlike other sensory systems, scent mostly bypasses the thalamic sensory gating filter)
  • Taste: regular mushroom taste, 2 Listerine strips immediately afterward (again to engage in potential memory retrieval). Nothing nauseating or stomach-troubling.
  • Auditory: listening to minimalist / contemporary classical music by Ludovico Einaudi
  • Visual: YouTube videos of fractal images & Islamic art
  • Social: 4 friends (3 of which are of the rationalist-tribe; all techies)

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    Plate of mushrooms and accompanying peach-nectarine body scent

Prior Cognitive State

  • Past drug experiences: 2 occasions of cannabis, few times alcohol, and 2 occasions of adderall. All minor experiences, none negative, and generally I strongly abstain from psychoactive drugs (even caffeine). No prior experience with psychedelics(!)
  • Mood: relatively optimistic and happy; no negative feelings
  • Beliefs: generally Fictionalist in ontology, though in recent years have experienced Platonist tendencies. Strongly grounded in an empirically-based, scientific-physicalist perspective. Strong sense of individuality + Selfhood. Not religious, nor spiritual, though upbringing was Roman Catholic.
  • Training: former academic neuroscience + pharmacologically-trained; current data science graduate student
  • Goals: to gain first-person experience of Klüver constants and re-establish/confirm any potential taxonomy of geometric forms (see here, here, and here for more)
  • Expectations: extremely skeptical that any fantastical effects might occur other than some random colors in the visual field, minor mood changes, minor memory + time effects such as retarded / slowed time, and maybe at most some Alice-in-Wonderland Syndrome perceptual-type effects. Hoping for experiences of strong and consistent + clearly defined Klüver constants, but skeptical they even exist. Skeptical of any notion of god-minds, communion with nature, dying and being reborn, and generally any spiritual or mystical experiences.


Real-Time Trip Report (unedited)

Time of Ingestion – 9:55 am, 02/15/2020

10:21 – First noticeable effect. Concentration lagging. Palms beginning to sweat. Starting to feel like it might be difficult to focus enough to write a report.
10:29 – REALLY strong physiological effect. Losing focus. Similar to being extremely tired(!). Sweat increasing (palms, pits, neck in that order). No visual or auditory hallucinations yet. Everyone else is laughing somewhat uncontrollably.
10:33 – First STRONG spike of losing concentration. Similar to being really tired or fainting.
10:36 – Another strong spike of losing consciousness. No hallucinations yet.
10:37 – Spike again. Increasing frequency now. One about every 15-20 seconds. Have to write this sentence in bursts, and memory is trying to keep up recovering my train of thought. Have to stop and now and then to
10:38 – First visual effectss! Tortoise shell-like fractal images. Hard to focus. Palms really really really sweaty, notice it as keyboard residue.
10:43 – Still hanging in there. Notice that friend’s response time is really late with around 2 minute delayss, not sure if that’s me or them? Extreme switching cost now between chrome tabs of writing and watching youtube vid.
10:46 – Switching cost too strong. Dilemma now between 3rd person documentation and 1st person immersion. Trying hrad.
10:47 – okay giving in to the experience now. too strong now
10:48 – laughter
10:48 does not make sense, really hard to type now, losing languge
50 trying hard to document. worried hwo to convey this
51 realizati not abot documnting 52 thats it 53 can i come back
54 latice structs 58 still here k
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Post-Trip Report

Total Trip Duration: ~6-7 hours

I’m writing this now being fully recovered and in my usual frame of mind. I’m going to start with how much I can remember…

Somewhat cognizant but before peak experience, I came back from one of my blackouts and saw one of my friends outside the cabin. I worried about their safety but realized that other people were going to take care of him. I also remember one of my friends constantly checking up on me. The strongest thought that I recall during the beginning of my experience was realizing that I had to let go of all this documentation, stop worrying about others and what other people think, and had to let go of this 3rd person perspective. I know this sounds somewhat monstrously misanthropic, but at the time of the experience I felt like that to pursue Truth I had to go further than everyone else even if that meant leaving them behind, and it was distracting to even have to jump back and forth between 1st and 3rd person perspective to focus on responding to other people during my brief moments of sanity to tell them I was ok when I could be delving deeper and deeper into the experience. This thought of leaving all thoughts of others behind to pursue the Truth reoccurred a few times as I began to get sucked into the vortex of patterns found in the wood grains of the floor and the curls of the carpet.

Linearity of experience was soon lost. I blinked in and out of existence. Time was definitely not unraveling like the constant forward stream I was used to and I felt like I was teleporting from one false reality to the next. I didn’t know in what order those events occurred. At this period I really wasn’t thinking, but more just passively viewing brief glimpses and snapshots of my body going through the motion. One moment I was in the kitchen. The next locked in the bathroom. The next on the living room floor. It’s such a shame that there’s a quirk in our language requiring me to express these as “next experiences” when in reality I did not experience them as having an order. I felt a really strong sense of déjà vu and reverse déjà vu tied to each of them, as if I’ve already done them before while also simultaneously knowing that I will be doing them in the future. It was really weird to have the feeling that you know you’ve already lived the future.

I blinked onto the bathroom floor. I thought why should I even look back and respond at all to the other people asking if I was okay when I finally have the chance to explore and find Truth with a capital T, and suddenly a strong sadness hit me. It was more of a feeling than a coherent logical thought, but the best way I can explain it was that it was a type of guilt that I’ll never be able to share this with my sister, my brother, my mom and dad, and then what will happen to my roommates, and then all my other friends and classmates around me, and how they’ll worry about me and so I told myself I’ll have to come back for them.

And so I tried to come back. Trying and wanting is such an interesting concept. It’s weird to desire language without being able to form a coherent line of thought or internal sentence in your head, but that is what I remember doing. How do you say to yourself that you want something without even being able to describe to yourself what that is? It seems desire may be more fundamental than internal language. Soon my linguistic centers began to reboot and I realized that this had to do with my memory chunks getting larger and allowing me to hold more in short term memory. Although seemingly primitive and simplistic, I can’t emphasize enough how this realization that memory and language were intertwined and recursively bootstrapping each other really helped soothe away any panic that I was totally lost.

I blinked into the kitchen. Time was becoming more linearly coherent now, but I kept blanking out and teleporting randomly throughout the kitchen. The thing was: I didn’t think of it as the same kitchen. I thought of it as different parallel realities of a kitchen that I recognize. I remember my friend offering me a chip and me trying so very hard to grasp that chip from her and hold on to that reality even if it was not the true real one, as if by merely believing by sheer force of will that I am actually grasping an object then made it concrete. I recall saying ‘trying to parse’. I strained with cognitive effort to stop teleporting. I remember asking everyone in each reality I blinked into whether or not this was the real one. “Wow, is this real?” became a repeating question tinted with wonder and surprise.

I blinked into the living room. Time was linear again, and it seems I began to be able to somewhat coherently reflect on the geometric patterns clouding my sight. I regretfully wished I could have focused on them more (as well as the apparently living, pulsating, and breathing floor beneath me and the shrinking and growing of my hands), but it was at this moment that I truly to the deep core of myself had the gut feeling that this reality wasn’t my original one. I honestly and wholeheartedly believed that this reality was a construct and that I was living out a simulation either in the mind of my true body in the real world (where I was probably in some coma in the hospital) or inhabiting the body of a different version of myself in a parallel universe. Everything felt false. Fake. Simulated. I was overcome with a Great Sadness that I didn’t know how to get back to my own original reality, and that I never said goodbye to the people I loved. And I was surprised because these melancholic emotions were of such strength to overcome my scientific training and any previous skepticism I once held.

I tried in vain to remember some mathematical way of proving you were living in a simulation, maybe something from information theory, or Tegmark’s mathematical universe, or something regarding speeds and frames of references and computational power being limited in an embedded simulated universe, but I could not for the life of me recall how to actually prove this to myself or what experiment to run. I remember, fuck man, I really should have worked out those thought experiments and proofs in depth because now I’m stuck.

However, it was on that thought of frames of references that I realized with some sadness and regret that maybe it’s not all that bad since how can I be the one to say one reality is more real and valid than the next? The best way I can convey this was that it was a somewhat mono no aware-type feeling. Even if this is a simulation in my mind or I’m in some parallel universe, why should I be any less happy? If someone spent their whole life creating their own meaning through something as removed from reality as art, or music, or pure math, and was able to live a fulfilling life, why should any particular version of myself be considered less meaningful just because this version of me possesses a memory of another me as an origin and potential branching-off point? Wasn’t another reality just as valid as the original one that I just came from? What made my old frame of reference special except for the mere fact of it being my origin? Why was I feeling this sense of sadness that I left it all behind to teleport to this version of reality? And then came the acceptance that if this reality was just as real except for my gut belief that it wasn’t, why shouldn’t I be able to simultaneously accept that gut feeling and move on and live in this version of reality?

And so I decided to live on, and within a few hours began to lose this sense that this was the false reality (although I really really wished I had a GoPro camera with me so that I could definitively prove to myself that I was in the correct reality). I began to have a newfound strong sense of empathy towards people with dissociative disorders. Thinking back on the experience, I think I primed myself for these thoughts when I kept switching between first-person and third-person perspectives, telling myself I couldn’t handle the switching cost any longer and that I should just immerse myself fully in the experience and forget about documenting this for other people, and why was I even submitting myself to the approval of others anyways because if there’s anyone who will have to go further in their exploration and sacrifice the chance to be with others then I guess I’ll just have to take up that burden.

Overall, I think the strong dissociative experience of thinking this reality was the fake simulated one had to do with maybe a couple of things. As mentioned before, one cause could have been the psychological priming induced by constantly switching between 1st and 3rd person ways of perceiving this event, creating the necessary emotional conditions of being simultaneously split between existing and being fully immersed in the present moment versus wanting to abstract / detach myself from the moment.

The second potential cause of the dissociation could have been due to my brain constantly blacking out and being rebooted in another physical part of the house. Because I had no memory of the continuity of how I got from one context to the next, this conditioned my brain to rationalize and register each separate event as a separate reality, probably falsely recognizing and incorrectly pattern matching these experiences as being more similar to a dream state where teleportation is normal, perceptions are distorted, and sequences of events are jumbled. This probably then began synthesizing the necessary eventual gut-belief that this reality was fake (because I subconsciously falsely pattern matched that it was similar to a dream).

Finally, I think the third potential contributor to the dissociation occurred when I was coming down from the experience and my brain went on overdrive trying to rationalize events. It might be possible that the more you are adept at creatively rationalizing things away the paradoxically worse you are at accepting this reality. Just having knowledge of potential parallel realities in physics, the simulation hypothesis that we might either be simulated in our heads or on a computer and may not realize it, the philosophy of solipsism, and knowing the neuroscience of how just freaking good the brain is at tricking itself that something is real, all created fertile conditions for my brain to interpret this reality as false.

Thinking back on the experience, I now have a newfound appreciation for memory and the continuity of experience, and their contribution to what it means to feel situated and embodied in this reality. If I were to do this again I would probably micro-dose so that I could still retain my linguistic faculties and linear way of reasoning in order to investigate the visual geometric effects in much greater scientific 3rd person POV-like rigor, focusing less on the semantic psychoanalytical content of the experience and more on the psychophysical optical effects (which was my original goal!). This really showed me how dependent the sense of Self was on the continuity of memory and experience and that maybe the Self really is composed of different smaller frames of reference generated by subnetworks in the brain (and hence is an ecology of momentary and brief snapshots / selves constantly going in and out of existence, both competing and coalescing in dynamic flux to make up the whole Self). Without the strong pillar that the continuity of singular memory provides to the host body that this community of selves inhabits, I think there really could be a binding problem for integrating these individual snapshots into a singular Selfhood and individual identity that persist through time that we call ‘I’.
Overall, I gained a much greater appreciation for continuity, the linear narrative of language intertwined with memory, and what it feels like on the inside of someone who is dissociated and thinks their surrounding reality is just a construct and not real. Also, the geometric images were really cool and I finally now understand why people say Google’s DeepDream art seems psychedelic, because looking into the mirror during the later stages of my trip confirmed that my face really did look like a globular, eyes-everywhere, and skewed proportioned / sized image!sIALPrcsO8TouJL3khCiXQ-small
Anyways, I really want to thank my friends that were with me on this trip and for constantly checking up on me to make sure I was okay. Rarely do I feel comfortable in the presence of other people and I’m glad I felt safe with you.

Thank you ❤️

Overall, I’d give my first experience with psychedelics a 7/10!


2-Week Post-Trip Report

So it’s been 2 weeks since ingestion and I just wanted to briefly report this one last interesting phenomenon for documentation’s sake.

Out of the 14 days post-trip, a little less than half of those nights (6 nights in total, distributed more heavily in the week immediately after the trip), I’ve had dreams that featured strongly self-referential phenomena. Within these dreams, my perceptual surroundings immediately reminded me of my aforementioned psychonautical experience of questioning my reality. These strong emotional realizations would then essentially cause my brain to kick itself out of the dream.

However, instead of truly waking up, I was still nested inside another dream in which I was imagining waking up. I usually went through 2-3 rounds of this false waking-up cycle until I finally surfaced into the real reality of the morning.

I thought it interesting for the first 2 nights, but after that it actually got really tiring always waking up questioning whether or not I’m really awake, and then having to go through the same motions of prepping for school/work knowing you’ve done that 2-3 times already in your head for the day.

What was funny though was that this always occurred around the same time each morning (my body has always naturally woken up at 5 am on the dot since high school), and in each iteration of the dream in which I falsely woke up I remember looking at my clock and seeing that it is 5 am. This would then lend me false-confidence and confirm that “ah, ok, I’m not in the dream anymore since I really do wake up at 5 am“. However, I think after enough times of this not working my brain finally came to learn that that was no longer a reliable indicator of the reality being real.

This skeptical realization finally got strong enough to be able to recall within my dream and act as an early kick-out mechanism that I eventually woke up closer and closer to my true ‘waking up point’. I remember going through the wake-up, look at the clock, remember that this no longer works, then immediately get kicked out, and wake up again, look at the clock, then remember this no longer works and get kicked out again, wake up, then look at the clock and finally get some inkling that this perception is a little different and realize that’s because I’m really waking up for real now. A rather fascinating experience!


Featured image by Nick Swanson

Posthuman Art: Towards Full-Spectrum Positive Valence Amplification

Everyone says love hurts, but that is not true. Loneliness hurts. Rejection hurts. Losing someone hurts. Envy hurts. Everyone gets these things confused with love, but in reality love is the only thing in this world that covers up all pain and makes someone feel wonderful again. Love is the only thing in this world that does not hurt.

 

― Meša Selimović


Excerpt from the wonderful conversation between Lucas Perry, Sam Barker, and David Pearce posted on June 24 (2020) at the Future of Life Institute Podcast (where Mike Johnson and I have previously participated). [Emphasis mine].


Lucas Perry: For this first section, I’m basically interested in probing the releases that you already have done, Sam, and exploring them and your inspiration for the track titles and the soundscapes that you’ve produced. Some of the background and context for this is that much of this seems to be inspired by and related to David’s work, in particular the Hedonistic Imperative. I’m at first curious to know, Sam, how did you encounter David’s work, and what does it mean for you?

Sam Barker: David’s work was sort of arriving in the middle of a series of realizations, and kind of coming from a starting point of being quite disillusioned with music, and a little bit disenchanted with the vagueness, and the terminology, and the imprecision of the whole thing. I think part of me has always wanted to be some kind of scientist, but I’ve ended up at perhaps not the opposite end, but quite far away from it.

Lucas Perry: Could explain what you mean by vagueness and imprecision?

Sam Barker: I suppose the classical idea of what making music is about has a lot to do with the sort of western idea of individualism and about self-expression. I don’t know. There’s this romantic idea of artists having these frenzied creative bursts that give birth to the wonderful things, that it’s some kind of struggle. I just was feeling super disillusioned with all of that. Around that time, 2014 or 15, I was also reading a lot about social media, reading about behavioral science, trying to figure what was going on in this arena and how people are being pushed in different directions by this algorithmic system of information distribution. That kind of got me into this sort of behavioral science side of things, like the addictive part of the variable-ratio reward schedule with likes. It’s a free dopamine dispenser kind of thing. This was kind of getting me into reading about behavioral science and cognitive science. It was giving me a lot of clarity, but not much more sort of inspiration. It was basically like music.

Dance music especially is a sort of complex behavioral science. You do this and people do that. It’s all deeply ingrained. I sort of imagine the DJ as a sort Skinner box operator pulling puppet strings and making people behave in different ways. Music producers are kind of designing clever programs using punishment and reward, or suspense and release, and controlling people’s behavior. The whole thing felt super pushy and not a very inspiring conclusion. Looking at the problem from a cognitive science point of view is just the framework that helped me to understand what the problem was in the first place, so this kind of problem of being manipulative. Behavioral science is kind of saying what we can make people do. Cognitive psychology is sort of figuring out why people do that. That was my entry point into cognitive psychology, and that was kind of the basis for Debiasing.

There’s always been sort of a parallel for me between what I make and my state of mind. When I’m in a more positive state, I tend to make things I’m happier with, and so on. Getting to the bottom of what tricks were, I suppose, with dance music. I kind of understood implicitly, but I just wanted to figure out why things worked. I sort of came to the conclusion it was to do with a collection of biases we have, like the confirmation bias, and the illusion of truth effect, and the mere exposure effect. These things are like the guardians of four/four supremacy. Dance music can be pretty repetitive, and we describe it sometimes in really aggressive terminology. It’s a psychological kind of interaction.

Cognitive psychology was leading me to Kaplan’s law of the instrument. The law of the instrument says that if you give a small boy a hammer, he’ll find that everything he encounters requires pounding. I thought that was a good metaphor. The idea is that we get so used to using tools in a certain way that we lose sight of what it is we’re trying to do. We act in the way that the tool instructs us to do. I thought, what if you take away the hammer? That became a metaphor for me, in a sense, that David clarified in terms of pain reduction. We sort of put these painful elements into music in a way to give this kind of hedonic contrast, but we don’t really consider that that might not be necessary. What happens when we abolish these sort of negative elements? Are the results somehow released from this process? That was sort of the point, up until discovering the Hedonistic Imperative.

I think what I was needing at the time was a sort of framework, so I had the idea that music was decision making. To improve the results, you have to ask better questions, make better decisions. You can make some progress looking at the mechanics of that from a psychology point of view. What I was sort of lacking was a purpose to frame my decisions around. I sort of had the idea that music was a sort of a valence carrier, if you like, and that it could be tooled towards a sort of a greater purpose than just making people dance, which was for Debiasing the goal, really. It was to make people dance, but don’t use the sort of deeply ingrained cues that people used to, and see if that works.

What was interesting was how broadly it was accepted, this first EP. There were all kinds of DJs playing it in techno, ambient, electro, all sorts of different styles. It reached a lot of people. It was as if taking out the most functional element made it more functional and more broadly appealing. That was the entry point to utilitarianism. There was sort of an accidentally utilitarian act, in a way, to sort of try and maximize the pleasure and minimize the pain. I suppose after landing in utilitarianism and searching for some kind of a framework for a sense of purpose in my work, the Hedonistic Imperative was probably the most radical, optimistic take on the system. Firstly, it put me in a sort of mindset where it granted permission to explore sort of utopian ideals, because I think the idea of pleasure is a little bit frowned upon in the art world. I think the art world turns its nose up at such direct cause and effect. The idea that producers could be paradise engineers of sorts, or the precursors to paradise engineers, that we almost certainly would have a role in a kind of sensory utopia of the future.

There was this kind of permission granted. You can be optimistic. You can enter into your work with good intentions. It’s okay to see music as a tool to increase overall wellbeing, in a way. That was kind of the guiding idea for my work in the studio. I’m trying, these days, to put more things into the system to make decisions in a more conscious way, at least where it’s appropriate to. This sort of notion of reducing pain and increasing pleasure was the sort of question I would ask at any stage of decision making. Did this thing that I did serve those ends? If not, take a step back and try a different approach.

There’s something else to be said about the way you sort of explore this utopian world without really being bogged down. You handle the objections in such a confident way. I called it a zero gravity world of ideas. I wanted to bring that zero gravity feeling to my work, and to see that technology can solve any problem in this sphere. Anything’s possible. All the obstacles are just imagined, because we fabricate these worlds ourselves. These are things that were really instructive for me, as an artist.

Lucas Perry: That’s quite an interesting journey. From the lens of understanding cognitive psychology and human biases, was it that you were seeing those biases in dance music itself? If so, what were those biases in particular?

Sam Barker: On both sides, on the way it’s produced and in the way it’s received. There’s sort of an unspoken acceptance. You’re playing a set and you take a kick drum out. That signals to people to perhaps be alert. The lighting engineer, they’ll maybe raise the lights a little bit, and everybody knows that the music is going into sort of a breakdown, which is going to end in some sort of climax. Then, at that point, the kick drum comes back in. We all know this pattern. It’s really difficult to understand why that works without referring to things like cognitive psychology or behavioral science.

Lucas Perry: What does the act of debiasing the reception and production of music look like and do to the music and its reception?

Sam Barker: The first part that I could control was what I put into it. The experiment was whether a debiased piece of dance music could perform the same functionality, or whether it really relies on these deeply ingrained cues. Without wanting to sort of pat myself on the back, it kind of succeeded in its purpose. It was sort of proof that this was a worthy concept.

Lucas Perry: You used the phrase, earlier, four/four. For people who are not into dance music, that just means a kick on each beat, which is ubiquitous in much of house and techno music. You’ve removed that, for example, in your album Debiasing. What are other things that you changed from your end, in the production of Debiasing, to debias the music from normal dance music structure?

Sam Barker: It was informing the structure of what I was doing so much that I wasn’t so much on a grid where you have predictable things happening. It’s a very highly formulaic and structured thing, and that all keys into the expectation and this confirmation bias that people, I think, get some kind of kick from when the predictable happens. They say, yep. There you go. I knew that was going to happen. That’s a little dopamine rush, but I think it’s sort of a cheap trick. I guess I was trying to get the tricks out of it, in a way, so figuring out what they were, and trying to reduce or eliminate them was the process for Debiasing.

Lucas Perry: That’s quite interesting and meaningful, I think. Let’s just take trap music. I know exactly how trap music is going to go. It has this buildup and drop structure. It’s basically universal across all dance music. Progressive house in the 2010s was also exactly like this. What else? Dubstep, of course, same exact structure. Everything is totally predictable. I feel like I know exactly what’s going to happen, having listened to electronic music for over a decade.

Sam Barker: It works, I think. It’s a tried and tested formula, and it does the job, but when you’re trying to imagine states beyond just getting a little kick from knowing what was going to happen, that’s the place that I was trying to get to, really.

Lucas Perry: After the release of Debiasing in 2018, which was a successful attempt at serving this goal and mission, you then discovered the Hedonistic Imperative by David Pearce, and kind of leaned into consequentialism, it seems. Then, in 2019, you had two releases. You had BARKER 001 and you had Utility. Now, Utility is the album which most explicitly adopts David Pearce’s work, specifically in the Hedonistic Imperative. You mentioned electronic dance producers and artists in general can be sort of the first wave of, or can perhaps assist in paradise engineering, insofar as that will be possible in the near to short terms future, given advancements in technology. Is that sort of the explicit motivation and framing around those two releases of BARKER 001 and Utility?

Sam Barker: BARKER 001 was a few tracks that were taken out of the running for the album, because they didn’t sort of fit the concept. Really, I knew the last track was kind of alluding to the album. Otherwise, it was perhaps not sort of thematically linked. Hopefully, if people are interested in looking more into what’s behind the music, you can lead people into topics with the concept. With Utility, I didn’t want to just keep exploring cognitive biases and unpicking dance music structurally. It’s sort of a paradox, because I guess the Hedonistic Imperative argues that pleasure can exist without purpose, but I really was striving for some kind of purpose with the pleasure that I was getting from music. That sort of emerged from reading the Hedonistic Imperative, really, that you can apply music to this problem of raising the general level of happiness up a notch. I did sort of worry that by trying to please, it wouldn’t work, that it would be something that’s too sickly sweet. I mean, I’m pretty turned off by pop music, and there was this sort of risk that it would end up somewhere like that. That’s it, really. Just looking for a higher purpose with my work in music.

Lucas Perry: David, do you have any reactions?

David Pearce: Well, when I encountered Utility, yes, I was thrilled. As you know, essentially I’m a writer writing in quite heavy sub-academic prose. Sam’s work, I felt, helps give people a glimpse of our glorious future, paradise engineering. As you know, the reviews were extremely favorable. I’m not an expert critic or anything like that. I was just essentially happy and thrilled at the thought. It deserves to be mainstream. It’s really difficult, I think, to actually evoke the glorious future we are talking about. I mean, I can write prose, but in some sense music can evoke paradise better, at least for many people, than prose.

And it continues on. I highly recommend listening to the whole podcast: it is wonderfully edited and musical pieces referenced in the interview are brought up in real time for you to listen to. Barker also made a playlist of songs specifically for this podcast, which are played during the second half of the recording. It is delightful to listen to music that you know was produced with the explicit purpose of increasing your wellbeing. A wholesome message at last! Amazing art inspired by the ideology of Paradise Engineering, arriving near you… very soon.



As an aside, I think that shared visions of paradise are really essential for solving coordination problems. So…

Please join me in putting on Barker’s track Paradise Engineering, closing your eyes, and imagining- in detail- what the creation of an Institute for Paradise Engineering on a grand scale would look like. What would a positive Manhattan Project of Consciousness entail? What is the shortest path for us to create such a large-scale initiative?

By the way: the song is only 4 minutes long. So its duration is perfect for you to use as a guiding and grounding piece of media for a positive DMT trip. Press “play” immediately after you vaporize the DMT, sit back, relax, and try to render in your mind a posthuman paradise in which Full-Spectrum Supersentient Superintelligence has won and the threat of Pure Replicators has been averted. If you do this, please let me know what you experience as a result.


Ps. It’s worth noting that Barker’s conception of art is highly aligned with QRI’s view of what art could be like. See, in particular, models 4 through 8 in our article titled Harmonic Society.


Featured image by Michael Aaron Coleman

QRI’s FAQ

These are the answers to the most Frequently Asked Questions about the Qualia Research Institute. (See also: the glossary).


(Organizational) Questions About the Qualia Research Institute

  • What type of organization is QRI?

    • QRI is a nonprofit research group studying consciousness based in San Francisco, California. We are a registered 501(c)(3) organization.

  • What is the relationship between QRI, Qualia Computing, and Opentheory?

    • Qualia Computing and Opentheory are the personal blogs of QRI co-founders Andrés Gómez Emilsson and Michael Johnson, respectively. While QRI was in its early stages, all original QRI research was initially published on these two platforms. However, from August 2020 onward, this is shifting to a unified pipeline centered on QRI’s website.

  • Is QRI affiliated with an academic institution or university?

    • Although QRI does collaborate regularly with university researchers and laboratories, we are an independent research organization. Put simply, QRI is independent because we didn’t believe we could build the organization we wanted and needed to build within the very real constraints of academia. These constraints include institutional pressure to work on conventional projects, to optimize for publication metrics, and to clear various byzantine bureaucratic hurdles. It also includes professional and social pressure to maintain continuity with old research paradigms, to do research within an academic silo, and to pretend to be personally ignorant of altered states of consciousness. It’s not that good research cannot happen under these conditions, but we believe good consciousness research happens despite the conditions in academia, not because of them, and the best use of resources is to build something better outside of them.

  • How does QRI align with the values of EA?

    • Effective Altruism (EA) is a movement that uses evidence and reason to figure out how to do the most good. QRI believes this aesthetic is necessary and important for creating a good future. We also believe that if we want to do the most good, foundational research on the nature of the good is of critical importance. Two frames we offer are Qualia Formalism and Sentientism. Qualia Formalism is the claim that experience has a precise mathematical description, that a formal account of experience should be the goal of consciousness research. Sentientism is the claim that value and disvalue are entirely expressed in the nature and quality of conscious experiences. We believe EA is enriched by both Qualia Formalism and Sentientism.

  • What would QRI do with $10 billion?

    • Currently, QRI is a geographically distributed organization with access to commercial-grade neuroimaging equipment. The first thing we’d do with $10 billion is set up a physical headquarters for QRI and buy professional-grade neuroimaging devices (fMRI, MEG, PET, etc.) and neurostimulation equipment. We’d also hire teams of full-time physicists, mathematicians, electrical engineers, computer scientists, neuroscientists, chemists, philosophers, and artists. We’ve accomplished a great deal on a shoestring budget, but it would be hard to overestimate how significant being able to build deep technical teams and related infrastructure around core research threads would be for us (and, we believe, for the growing field of consciousness research). Scaling is always a process and we estimate our ‘room for funding’ over the next year is roughly ~$10 million. However, if we had sufficiently deep long-term commitments, we believe we could successfully scale both our organization and research paradigm into a first-principles approach for decisively diagnosing and curing most forms of mental illness. We would continue to run studies and experiments, collect interesting data about exotic and altered states of consciousness, pioneer new technologies that help eliminate involuntary suffering, and develop novel ways to enable conscious beings to safely explore the state-space of consciousness.

Questions About Our Research Approach

  • What differentiates QRI from other research groups studying consciousness?

    • The first major difference is that QRI breaks down “solving consciousness” into discrete subtasks; we’re clear about what we’re trying to do, which ontologies are relevant for this task, and what a proper solution will look like. This may sound like a small thing, but an enormous amount of energy is wasted in philosophy by not being clear about these things. This lets us “actually get to work.”

    • Second, our focus on valence is rare in the field of consciousness studies. A core bottleneck in understanding consciousness is determining what its ‘natural kinds’ are: terms which carve reality at the joints. We believe emotional valence (the pleasantness/unpleasantness of an experience) is one such natural kind, and this gives us a huge amount of information about phenomenology. It also offers a clean bridge for interfacing with (and improving upon) the best neuroscience.

    • Third, QRI takes exotic states of consciousness extremely seriously whereas most research groups do not. An analogy we make here is that ignoring exotic states of consciousness is similar to people before the scientific enlightenment thinking that they can understand the nature of energy, matter, and the physical world just by studying it at room temperature while completely ignoring extreme states such as what’s happening in the sun, black holes, plasma, or superfluid helium. QRI considers exotic states of consciousness as extremely important datapoints for reverse-engineering the underlying formalism for consciousness.

    • Lastly, we have a focus on precise, empirically testable predictions, which is rare in philosophy of mind. Any good theory of consciousness should also contribute to advancements in neuroscience. Likewise, any good theory of neuroscience should contribute to novel, bold, falsifiable predictions, and blueprints for useful things, such as new forms of therapy. Having such a full-stack approach to consciousness which does each of those two things is thus an important marker that “something interesting is going on here” and is simply very useful for testing and improving theory.

  • What methodologies are you using? How do you actually do research? 

    • QRI has three core areas of research: philosophy, neuroscience, and neurotechnology 

      • Philosophy: Our philosophy research is grounded in the eight problems of consciousness. This divide-and-conquer approach lets us explore each subproblem independently, while being confident that when all piecemeal solutions are added back together, they will constitute a full solution to consciousness.

      • Neuroscience: We’ve done original synthesis work on combining several cutting-edge theories of neuroscience (the free energy principle, the entropic brain, and connectome-specific harmonic waves) into a unified theory of Bayesian emotional updating; we’ve also built the world’s first first-principles method for quantifying emotional valence from fMRI. More generally, we focus on collecting high valence neuroimaging datasets and developing algorithms to analyze, quantify, and visualize them. We also do extensive psychophysics research, focusing on both the fine-grained cognitive-emotional effects of altered states, and how different types of sounds, pictures, body vibrations, and forms of stimulation correspond with low and high valence states of consciousness.

      • Neurotechnology: We engage in both experimentation-driven exploration, tracking the phenomenological effects of various interventions, as well as theory-driven development. In particular, we’re prototyping a line of neurofeedback tools to help treat mental health disorders.

  • What does QRI hope to do over the next 5 years? Next 20 years?

    • Over the next five years, we intend to further our neurotechnology to the point that we can treat PTSD (post-traumatic stress disorder), especially treatment-resistant PTSD. We intend to empirically verify or falsify the symmetry theory of valence. If it is falsified, we will search for a new theory that ties together all of the empirical evidence we have discovered. We aim to create an Effective Altruist cause area regarding the reduction of intense suffering as well as the study of very high valence states of consciousness.

    • Over the next 20 years, we intend to become a world-class research center where we can put the discipline of “paradise engineering” (as described by philosopher David Pearce) on firm academic grounds.

Questions About Our Mission

  • How can understanding the science of consciousness make the world a better place?

    • Understanding consciousness would improve the world in a tremendous number of ways. One obvious outcome would be the ability to better predict what types of beings are conscious—from locked-in patients to animals to pre-linguistic humans—and what their experiences might be like.

    • We also think it’s useful to break down the benefits of understanding consciousness in three ways: reducing the amount of extreme suffering in the world, increasing the baseline well-being of conscious beings, and achieving new heights for what conscious states are possible to experience.

    • Without a good theory of valence, many neurological disorders will remain completely intractable. Disorders such as fibromyalgia, complex regional pain syndrome (CRPS), migraines, and cluster headaches are all currently medical puzzles and yet have incredibly negative effects on people’s livelihoods. We think that a mathematical theory of valence will explain why these things feel so bad and what the shortest path for getting rid of them looks like. Besides valence-related disorders, nearly all mental health disorders, from clinical depression and PTSD to schizophrenia and anxiety disorders, will become better understood as we discover the structure of conscious experience.

    • We also believe that many (though not all) of the zero-sum games people play are the products of inner states of dissatisfaction and suffering. Broadly speaking, people who have a surplus of cognitive and emotional energy tend to play more positive sum games, are more interested in cooperation, and are very motivated to do so. We think that studying states such as those induced by MDMA that combine both high valence and a prosocial behavior mindset can radically alter the game theoretical landscape of the world for the better.

  • What is the end goal of QRI? What does QRI’s perfect world look like?

    • In QRI’s perfect future:

      • There is no involuntary suffering and all sentient beings are animated by gradients of bliss,

      • Research on qualia and consciousness is done at a very large scale for the purpose of mapping out the state-space of consciousness and understanding its computational and intrinsic properties (we think that we’ve barely scratched the surface of knowledge about consciousness),

      • We have figured out the game-theoretical subtleties in order to make that world dynamic yet stable: radically positive, without just making it fully homogeneous and stuck in a local maxima.

Questions About Getting Involved

  • How can I follow QRI’s work?

    • You can start by signing up for our newsletter! This is by far our most important communication channel. We also have a Facebook page, Twitter account, and Linkedin page. Lastly, we share some exclusive tidbits of ideas and thoughts with our supporters on Patreon.

  • How can I get involved with QRI?

    • The best ways to help QRI are to:

      • Donate to help support our work.

      • Read and engage with our research. We love critical responses to our ideas and encourage you to reach out if you have an interesting thought!

      • Spread the word to friends, potential donors, and people that you think would make great collaborators with QRI.

      • Check out our volunteer page to find more detailed ways that you can contribute to our mission, from independent research projects to QRI content creation.

Questions About Consciousness

  • What assumptions about consciousness does QRI have? What theory of consciousness does QRI support?

    • The most important assumption that QRI is committed to is Qualia Formalism, the hypothesis that the internal structure of our subjective experience can be represented precisely by mathematics. We are also Valence Realists: we believe valence (how good or bad an experience feels) is a real and well-defined property of conscious states. Besides these positions, we are fairly agnostic and everything else is an educated guess useful for pragmatic purposes.

  • What does QRI think of functionalism?

    • QRI thinks that functionalism takes many high-quality insights about how systems work and combines them in such a way that both creates confusion and denies the possibility of progress. In its raw, unvarnished form, functionalism is simply skepticism about the possibility of Qualia Formalism. It is simply a statement that “there is nothing here to be formalized; consciousness is like élan vital, confusion to be explained away.” It’s not actually a theory of consciousness; it’s an anti-theory. This is problematic in at least two ways:

      • 1. By assuming consciousness has formal structure, we’re able to make novel predictions that functionalism cannot (see e.g. QRI’s Symmetry Theory of Valence, and Quantifying Bliss). A few hundred years ago, there were many people who doubted that electromagnetism had a unified, elegant, formal structure, and this was a reasonable position at the time. However, in the age of the iPhone, skepticism that electricity is a “real thing” that can be formalized is no longer reasonable. Likewise, everything interesting and useful QRI builds using the foundation of Qualia Formalism stretches functionalism’s credibility thinner and thinner.

      • 2. Insofar as functionalism is skeptical about the formal existence of consciousness, it’s skeptical about the formal existence of suffering and all sentience-based morality. In other words, functionalism is a deeply amoral theory, which if taken seriously dissolves all sentience-based ethical claims. This is due to there being an infinite number of functional interpretations of a system: there’s no ground-truth fact of the matter about what algorithm a physical system is performing, about what information-processing it’s doing. And if there’s no ground-truth about which computations or functions are present, but consciousness arises from these computations or functions, then there’s no ground-truth about consciousness, or things associated with consciousness, like suffering. This is a strange and subtle point, but it’s very important. This point alone is not sufficient to reject functionalism: if the universe is amoral, we shouldn’t hold a false theory of consciousness in order to try to force reality into some ethical framework. But in debates about consciousness, functionalists should be up-front that functionalism and radical moral anti-realism is a package deal, that inherent in functionalism is the counter-intuitive claim that just as we can reinterpret which functions a physical system is instantiating, we can reinterpret what qualia it’s experiencing and whether it’s suffering.

    • For an extended argument, see Against Functionalism.

  • What does QRI think of panpsychism?

    • At QRI, we hold a position that is close to dual-aspect monism or neutral monism, which states that the universe is composed of one kind of thing that is neutral, and that both the mental and physical are two features of this same substance. One of the motivating factors for holding this view is that if there is deep structure in the physical, then there should be a corresponding deep structure to phenomenal experience. And we can tie this together with physicalism in the sense that the laws of physics ultimately describe fields of qualia. While there are some minor disagreements between dual-aspect monism and panpsychism, we believe that our position mostly fits well with a panpsychist view—that phenomenal properties are a fundamental feature of the world and aren’t spontaneously created only when a certain computation is being performed.

    • However, even with this view, there still are very important questions, such as: what makes a unified conscious experience? Where does one experience end and another begin? Without considering these problems in the light of Qualia Formalism, it is easy to tie animism into panpsychism and believe that inanimate objects like rocks, sculptures, and pieces of wood have spirits or complex subjective experiences. At QRI, we disagree with this and think that these types of objects might have extremely small pockets of unified conscious experience, but will mostly be masses of micro-qualia that are not phenomenally bound into some larger experience.

  • What does QRI think of IIT (Integrated Information Theory)?

    • QRI is very grateful for IIT because it is the first mainstream theory of consciousness that satisfies a Qualia Formalist account of experience. IIT says (and introduced the idea!) that for every conscious experience, there is a corresponding mathematical object such that the mathematical features of that object are isomorphic to the properties of the experience. QRI believes that without this idea, we cannot solve consciousness in a meaningful way, and we consider the work of Giulio Tononi to be one of our core research lineages. That said, we are not in complete agreement with the specific mathematical and ontological choices of IIT, and we think it may be trying to ‘have its cake and eat it too’ with regard to functionalism vs physicalism. For more, see Sections III-V of Principia Qualia.

    • We make no claim that some future version of IIT, particularly something more directly compatible with physics, couldn’t cleanly address our objections, and see a lot of plausible directions and promise in this space.

  • What does QRI think of the free energy principle and predictive coding?

    • On our research lineages page, we list the work of Karl Friston as one of QRI’s core research lineages. We consider the free energy principle (FEP), as well as related research such as predictive coding, active inference, the Bayesian brain, and cybernetic regulation, as an incredibly elegant and predictive story of how brains work. Friston’s idea also forms a key part of the foundation for QRI’s theory of brain self-organization and emotional updating, Neural Annealing.

    • However, we don’t think that the free energy principle is itself a theory of consciousness, as it suffers from many of the shortcomings of functionalism: we can tell the story about how the brain minimizes free energy, but we don’t have a way of pointing at the brain and saying *there* is the free energy! The FEP is an amazing logical model, but it’s not directly connected to any physical mechanism. It is a story that “this sort of abstract thing is going on in the brain” without a clear method of mapping this abstract story to reality.

    • Friston has supported this functionalist interpretation of his work, noting that he sees consciousness as a process of inference, not a thing. That said, we are very interested in his work on calculating the information geometry of Markov blankets, as this could provide a tacit foundation for a formalist account of qualia under the FEP. Regardless of this, though, we believe Friston’s work will play a significant role in a future science of mind.

  • What does QRI think of global workspace theory?

    • The global workspace theory (GWT) is a cluster of empirical observations that seem to be very important for understanding what systems in the brain contribute to a reportable experience at a given point in time. The global workspace theory is a very important clue for answering questions of what philosophers call Access Consciousness, or the aspects of our experience on which we can report.

    • However, QRI does not consider the global workspace theory to be a full theory of consciousness. Parts of the brain that are not immediately contributing to the global workspace may be composed of micro qualia, or tiny clusters of experience. They’re obviously impossible to report on, but they are still relevant to the study of consciousness. In other words, just because a part of your brain wasn’t included in the instantaneous global workspace, doesn’t mean that it can’t suffer or it can’t experience happiness. We value global workspace research because questions of Access Consciousness are still very critical for a full theory of consciousness.

  • What does QRI think of higher-order theories of consciousness?

    • QRI is generally opposed to theories of consciousness that equate consciousness with higher order reflective thought and cognition. Some of the most intense conscious experiences are pre-reflective or unreflective such as blind panic, religious ecstasy, experiences of 5-MeO-DMT, and cluster headaches. In these examples, there is not much reflectivity nor cognition going on, yet they are intensely conscious. Therefore, we largely reject any attempt to define consciousness with a higher-order theory.

  • What is the relationship between evolution and consciousness?

    • The relationship between evolution and consciousness is very intricate and subtle. An eliminativist approach arrives at the simple idea that information processing of a certain type is evolutionarily advantageous, and perhaps we can call this consciousness. However, with a Qualia Formalist approach, it seems instead that the very properties of the mathematical object isomorphic to consciousness can play key roles (either causal or in terms of information processing) that make it advantageous for organisms to recruit consciousness.

    • If you don’t realize that consciousness maps onto a mathematical object with properties, you may think that you understand why consciousness was recruited by natural selection, but your understanding of the topic would be incomplete. In other words, to have a full understanding of why evolution recruited consciousness, you need to understand what advantages the mathematical object has. One very important feature of consciousness is its capacity for binding. For example, the unitary nature of experience—the fact that we can experience a lot of qualia simultaneously—may be a key feature of consciousness that accelerates the process of finding solutions to constraint satisfaction problems. In turn, evolution would hence have a reason to recruit states of consciousness for computation. So rather than thinking of consciousness as identical with the computation that is going on in the brain, we can think of it as a resource with unique computational benefits that are powerful and dynamic enough to make organisms that use it more adaptable to their environments.

  • Does QRI think that animals are conscious?

    • QRI thinks there is a very high probability that every animal with a nervous system is conscious. We are agnostic about unified consciousness in insects, but we consider it very likely. We believe research on animal consciousness has relevance when it comes to treating animals ethically. Additionally, we do think that the ethical importance of consciousness has more to do with the pleasure-pain axis (valence), rather than cognitive ability. In that sense, the suffering of non-human animals may be just as morally relevant, if not more relevant than humans. The cortex seems to play a largely inhibitory role for emotions, such that the larger the cortex is, the better we’re able to manage and suppress our emotions. Consequently, animals whose cortices are less developed than ours may experience pleasure and pain in a more intense and uncontrollable way, like a pre-linguistic toddler.

  • Does QRI think that plants are conscious?

    • We think it’s very unlikely that plants are conscious. The main reason is that they lack an evolutionary reason to recruit consciousness. Large-scale phenomenally bound experience may be very energetically expensive, and plants don’t have much energy to spare. Additionally, plants have thick cellulose walls that separate individual cells, making it very unlikely that plants can solve the binding problem and therefore create unified moments of experience.

  • Why do some people seek out pain?

    • This is a very multifaceted question. As a whole, we postulate that in the vast majority of cases, when somebody may be nominally pursuing pain or suffering, they’re actually trying to reduce internal dissonance in pursuit of consonance or they’re failing to predict how pain will actually feel. For example, when a person hears very harsh music, or enjoys extremely spicy food, this can be explained in terms of either masking other unpleasant sensations or raising the energy parameter of experience, the latter of which can lead to neural annealing: a very pleasant experience that manifests as consonance in the moment.

  • I sometimes like being sad. Is QRI trying to take that away from me?

    • Before we try to ‘fix’ something, it’s important to understand what it’s trying to do for us. Sometimes suffering leads to growth; sometimes creating valuable things involves suffering. Sometimes, ‘being sad’ feels strangely good. Insofar as suffering is doing good things for us, or for the world, QRI advocates a light touch (see Chesterton’s fence). However, we also suggest two things:

      • 1. Most kinds of melancholic or mixed states of sadness usually are pursued for reasons that cash out as some sort of pleasure. Bittersweet experiences are far more preferable than intense agony or deep depression. If you enjoy sadness, it’s probably because there’s an aspect of your experience that is enjoyable. If it were possible to remove the sad part of your experience while maintaining the enjoyable part of it, you might be surprised to find that you prefer this modified experience more than the original one.

      • 2. There are kinds of sadness and suffering that are just bad, that degrade us as humans, and would be better to never feel. QRI doesn’t believe in forcibly taking away voluntary suffering, or pushing bliss on people. But we would like to live in a world where people can choose to avoid such negative states, and on the margin, we believe it would be better for humanity for more people to be joyful, filled with a deep sense of well-being.

  • If dissonance is so negative, why is dissonance so important in music?

    • When you listen to very consonant music or consonant tones, you will quickly adapt to these sounds and get bored of them. This has nothing to do with consonance itself being unpleasant and everything to do with learning in the brain. Whenever you experience the same stimuli repeatedly, most brains will trigger a boredom mechanism and add dissonance of its own in order to make you enjoy the stimuli less or simply inhibit it, not allowing you to experience it at all. Semantic satiation is a classic example of this where repeating the same word over and over will make it lose its meaning. For this reason, to trigger many high valence states of consciousness consecutively, you need contrast. In particular, music works with gradients of consonance and dissonance, and in most cases, moving towards consonance is what feels good rather than the absolute value of consonance. Music tends to feel the best when you mix a high absolute value of consonance together with a very strong sense of moving towards an even higher absolute value of consonance. Playing some levels of dissonance during a song will later enhance the enjoyment of the more consonant parts such as the chorus of songs, which are reported to be the most euphoric parts of song and typically are extremely consonant.

  • What is QRI’s perspective on AI and AI safety research?

    • QRI thinks that consciousness research is critical for addressing AI safety. Without a precise way of quantifying an action’s impact on conscious experiences, we won’t be able to guarantee that an AI system has been programmed to act benevolently. Also, certain types of physical systems that perform computational tasks may be experiencing negative valence without any outside observer being aware of it. We need a theory of what produces unpleasant experiences to avoid inadvertently creating superintelligences that suffer intensely in the process of solving important problems or accidentally inflict large-scale suffering.

    • Additionally, we think that a very large percentage of what will make powerful AI dangerous is that the humans programming these machines and using these machines may be reasoning from states of loneliness, resentment, envy, or anger. By discovering ways to help humans transition away from these states, we can reduce the risks of AI by creating humans that are more ethical and aligned with consciousness more broadly. In short: an antidote for nihilism could lead to a substantial reduction in existential risk.

    • One way to think about QRI and AI safety is that the world is building AI, but doesn’t really have a clear, positive vision of what to do with AI. Lacking this, the default objective becomes “take over the world.” We think a good theory of consciousness could and will offer new visions of what kind of futures are worth building—new Schelling points that humanity (and AI researchers) could self-organize around.

  • Can digital computers implementing AI algorithms be conscious?

    • QRI is agnostic about this question. We have reasons to believe that digital computers in their current form cannot solve the phenomenal binding problem. Most of the activity in digital computers can be explained in a stepwise fashion in terms of localized processing of bits of information. Because of this, we believe that current digital computers could be creating fragments of qualia, but are unlikely to be creating strongly globally bound experiences. So, we consider the consciousness of digital computers unlikely, although given our current uncertainty over the Binding Problem (or alternatively framed, the Boundary Problem), this assumption is lightly held. In the previous question, when we write that “certain types of physical systems that perform computational tasks may be experiencing negative valence”, we assume that these hypothetical computers have some type of unified conscious experience as a result of having solved the phenomenal binding problem. For more on this topic, see: “What’s Out There?

  • How much mainstream recognition has QRI’s work received, either for this line of research or others? Has it published in peer-reviewed journals, received any grants, or garnered positive reviews from other academics?

    • We are collaborating with researchers from Johns Hopkins University and Stanford University on several studies involving the analysis of neuroimaging data of high-valence states of consciousness. Additionally, we are currently preparing two publications for peer-reviewed journals on topics from our core research areas. Michael Johnson will be presenting at this year’s MCS seminar series, along with Karl Friston, Anil Seth, Selen Atasoy, Nao Tsuchiya, and others; Michael Johnson, Andrés Gómez Emilsson, and Quintin Frerichs have also given invited talks at various east-coast colleges (Harvard, MIT, Princeton, and Dartmouth).

    • Some well-known researchers and intellectuals that are familiar and think positively about our work include: Robin Carhart-Harris, Scott Alexander, David Pearce, Steven Lehar, Daniel Ingram, and more. Scott Alexander acknowledged that QRI put together the paradigms that contributed to Friston’s integrative model of how psychedelics work before his research was published. Our track record so far has been to foreshadow (by several years in advance) key discoveries later proposed and accepted in mainstream academia. Given our current research findings, we expect this trend to continue in the years to come.

Miscellaneous

  • How does QRI know what is best for other people/animals? What about cultural relativism?

    • We think that, to a large extent, people and animals work under the illusion that they are pursuing intentional objects, states of the external environment, or relationships that they may have with the external environment. However, when you examine these situations closely, you realize that what we actually pursue are states of high valence triggered by external circumstances. There may be evolutionary and cultural selection pressures that push us toward self-deception as to how we actually function. And we consider it negative to have these selection pressures makes us less self-aware because it often focuses our energy on unpleasant, destructive, or fruitless strategies. QRI hopes to support people in fostering more self-awareness, which can come through experiments with one’s own consciousness, like meditation, as well as through the deeper theoretical understanding of what it is that we actually want.

  • How central is David Pearce’s work to the work of the QRI?

    • We consider David Pearce to be one of our core lineages. We particularly value his contribution to valence realism, the insistence that states of consciousness come with an overall valence, and that this is very morally relevant. We also consider David Pearce to be very influential in philosophy of mind; Pearce, for instance, coined the phrase ‘tyranny of the intentional object’, the title of a core QRI piece of the same name. We have been inspired by Pearce’s descriptions for what any scientific theory of consciousness should be able to explain, as well as his particular emphasis on the binding problem. David’s vision of a world animated by ‘gradients of bliss’ has also been very generative as a normative thought experiment which integrates human and non-human well-being. We do not necessarily agree with all of David Pearce’s work, but we respect him as an insightful and vivid thinker who has been brave enough to actually take a swing at describing utopia and who we believe is far ahead of his time.

  • What does QRI think of negative utilitarianism?

    • There’s general agreement within QRI that intense suffering is an extreme moral priority, and we’ve done substantial work on finding simple ways of getting rid of extreme suffering (with our research inspiring at least one unaffiliated startup to date). However, we find it premature to strongly endorse any pre-packaged ethical theory, especially because none of them are based on any formalism, but rather an ungrounded concept of ‘utility’. The value of information here seems enormous, and we hope that we can get to a point where the ‘correct’ ethical theory may simply ‘pop out of the equations’ of reality. It’s also important to highlight the fact that common versions and academic formulations of utilitarianism seem to be blind to many subtleties concerning valence. For example, they do not distinguish between mixed states of consciousness where you have extreme pleasure combined with extreme suffering in such a way that you judge the experience to be neither entirely suffering nor entirely happiness and states of complete neutrality, such as extreme white noise. Because most formulations of utilitarianism do not distinguish between them, we are generally suspicious of the idea that philosophers of ethics have considered all of the relevant attributes of consciousness in order to make accurate judgments about morality.

  • What does QRI think of philosophy of mind departments?

    • We believe that the problems that philosophy of mind departments address tend to be very disconnected from what truly matters from an ethical, moral, and philosophical point of view. For example, there is little appreciation of the value of bringing mathematical formalisms into discussions about the mind, or what that might look like in practice. Likewise there is close to no interest in preventing extreme suffering nor understanding its nature. Additionally, there is usually a disregard for extreme states of positive valence, and strange or exotic experiences in general. It may be the case that there are worthwhile things happening in departments and classes creating and studying this literature, but we find them characterized by processes which are unlikely to produce progress on their nominal purpose, creating a science of mind.

    • In particular, in academic philosophy of mind, we’ve seen very little regard for producing empirically testable predictions. There are millions of pages written about philosophy of mind, but the number of pages that provide precise, empirically testable predictions is quite thin.

  • What therapies does QRI recommend for depression, anxiety, and chronic pain?

    • At QRI, we do not make specific recommendations to individuals, but rather point to areas of research that we consider to be extremely important, tractable, and neglected, such as anti-tolerance drugs, neural annealing techniques, frequency specific microcurrent for kidney stone pain, and N,N-DMT and other tryptamines for cluster headaches and migraines.

  • Why does QRI think it’s so important to focus on ending extreme suffering? 

    • QRI thinks ending extreme suffering is important, tractable, and neglected. It’s important because of the logarithmic scales of pleasure and pain—the fact that extreme suffering is far worse by orders of magnitude than what people intuitively believe. It’s tractable because there are many types of extreme suffering that have existing solutions that are fairly trivial or at least have a viable path for being solved with moderately funded research programs. And it’s neglected mostly because people are unaware of the existence of these states, though not necessarily because of their rarity. For example, 10% of the population experiences kidney stones at some point in their life, but for reasons having to do with trauma, PTSD, and the state-dependence of memory, even people who have suffered from kidney stones do not typically end up dedicating their time or resources toward eradicating them.

    • It’s also likely that if we can meaningfully improve the absolute worst experiences, much of the knowledge we’ll gain in that process will translate into other contexts. In particular, we should expect to figure out how to make moderately depressed people happier, fix more mild forms of pain, improve the human hedonic baseline, and safely reach extremely great peak states. Mood research is not a zero-sum game. It’s a web of synergies.



Many thanks to Andrew Zuckerman, Mackenzie Dion, and Mike Johnson for their collaboration in putting this together. Featured image is QRI’s logo – animated by Hunter Meyer.

5-MeO-DMT vs. N,N-DMT: The 9 Lenses

TL;DR

Some substances seem to be much better at treating psychological trauma than others, even when they are seemingly similar in nature. We have reason to believe that 5-MeO-DMT is significantly better suited for this task than N,N-DMT (“DMT” from now on). In order to gain insight into why this difference exists, we investigate the phenomenological differences and similarities between the experiences produced by these two tryptamine psychedelics. In particular, we develop 9 lenses that show promise for understanding how 5-MeO-DMT and DMT differ:

  1. Space vs. Form: 5-MeO is more space-like than DMT.
  2. Crystals vs. Quasi-Crystals: 5-MeO generates more perfectly repeating rhythms and hallucinations than DMT.
  3. Non-Attachment vs. Attachment: 5-MeO seems to enable detachment from the craving of both existence and non-existence, whereas DMT enhances the craving.
  4. Underfitting vs. Overfitting: 5-MeO reduces one’s model complexity whereas DMT radically increases it.
  5. Fixed Points and Limit Cycles vs. Chaotic Attractors: 5-MeO’s effect on feedback leads to stable and predictable attractors while DMT’s attractors are inherently chaotic.
  6. Modulation of Lateral Inhibition: 5-MeO may reduce lateral inhibition while DMT may enhance it.
  7. Diffuse Attention vs. Focused Attention: 5-MeO diffuses attention uniformly over large regions of one’s experiential field, while DMT seems to focus it.
  8. Big Chunks and Tiny Chunks vs. A Power Law of Chunks: 5-MeO creates a few huge phases of experience (as in phases of matter) with a few remaining specks, while DMT produces a more organic power law distribution of chunk sizes.
  9. Integration vs. Fragmentation: 5-MeO seems to give rise to “neural integration” involving the entrainment of any two arbitrary subnetworks (even when they usually do not talk to each other), while DMT fragments communication between most networks but massively enhances it between some specific kinds of networks.

All of this together suggests that 5-MeO-DMT is better at helping you “reconnect with yourself” than DMT. And this may be key to treating trauma effectively.


What is Trauma?

I will start out by briefly mentioning an interesting property of psychological trauma. You see, trauma has a lot of somatic manifestations. Feeling disconnected from yourself,  like you are full of blockages, that you have numb regions in your body despite no physical damage, and so on, are all quintessential ways in which trauma shows up in a person’s everyday life. Given these manifestations, do these suggest any new way of treating this? How about using something that facilitates the communication between parts of your nervous system that are not on “speaking terms” with each other? Would giving our nervous system a kind of vibration that simultaneously entrains any two of its regions to make them act as a unit be of any help?


Psychotropic Treatment of Trauma

Based on tens of interviews, hundreds of trip reports, and a literature review, I have arrived at a tentative short list of drugs that have the highest potential to heal trauma (in decreasing order):

  1. 5-MeO-DMT
  2. MDMA
  3. Ketamine

They are all synergistic combined with music, vibration, strobes, and olfaction. And when wisely used, they all have the ability to help you move on past pain: stop ruminating, stop feeling like your behavior is inhibited, and stop having panic attacks associated with your past experiences.

At some point in the future I will provide direct empirical evidence for the claim that these three substances are uniquely good for treating trauma. Arguably psilocybin, ayahuasca, and LSD can be helpful in processing traumatic experiences too. But my claim is that the options I listed are uniquely good at deeply resolving the issues at an emotional level and bringing to you the opportunity to feel a profound and lasting sense of inner peace.

DMT won’t help as much as 5-MeO-DMT.

MDA is not as good as MDMA.

And DXM, ok, perhaps it can also be quite useful for trauma… but ketamine has something “extra” that really helps.

What is this?


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The Koan: 5-MeO-DMT, MDMA, Ketamine?

Perhaps we could gain a new perspective by framing this as a Koan: what do MDMA, 5-MeO-DMT, and ketamine have in common? You HAVE to the figure this out in the next 24 hours, or your guru will literally cut your cat in half. Motivated enough?

What do you do? Well, you start out by borrowing psychopharmacology books from the library. But does that help? When it comes to trauma, in traditional textbook neuroscience MDMA is at best just a footnote. Ketamine is not even mentioned for the most part, unless the book is hip, but even then it will be mentioned in the chapter about anaesthetics and painkillers; its psychoactive effects will be glossed over as “emergent phenomena”. No! What are you doing? Wasn’t John C. Lilly already talking about the far-out, extraordinarily bizarre, perhaps even literally inter-dimensional properties of “vitamin K” way back in the 70s? Then why is my 2007 “Drugs and the Brain” textbook so totally lacking in any kind of genuine phenomenological insight about this stuff?

And what about 5-MeO-DMT? You are lucky if the term appears even once in your $800 textbook. And if it does indeed appear, you can bet it will also be in a footnote, this time concerning matters such as “psychoactive animals”, “other tryptamines”, and “mesoamerican entheogens”. You will neither see 5-MeO-DMT mentioned in a personal identity philosophy textbook, nor in a neuroscience treatise on “neural synchrony”, nor in the part of academia focused on “innovation in the treatment of mental illness”.

It is sad to admit, but the official main-lined level of interest in the three most promising therapeutic tools for trauma listed above is a matter of sorting and assembling footnotes.

I am exaggerating a bit, of course.

MDMA’s therapeutic potential is gaining traction thanks to the tireless work of MAPS. S-Ketamine is now approved as an anti-depressant. And while 5-MeO-DMT is gaining popularity at a glacial pace, it is at this point by no means a secret. An increasing number of vocal members of the psychedelic community have been talking about 5-MeO-DMT for some years. People who have publicly emphasized how different five is from other psychedelics include Hamilton Morris, James Oroc, Martin Ball, Leo Gura, and Rak Razam. But what we still lack is rigorous scientific backing for these claims. After all, everyone is likely to want to sell their aesthetic preferences as universal truths about beauty and bliss, right? Thankfully, there are some early scientific indications already:

The above graph comes from a 2018 study that investigated the therapeutic effects of 5-MeO-DMT-containing toad venom relative to psilocybin. The dose used (the amount of buffo venom vaporized) had an estimated content of 5-7mg of 5-MeO-DMT, and the researchers classified 75% of the resulting experiences as meeting the criteria for a “complete mystical experience”. It measured people’s level of response with the Mystical Experiences Questionnaire (MEQ30), and as you can see from the graph above, in every category 5-MeO-DMT seems to be more powerful than psilocybin. The level of effectiveness was indeed found to be higher than all but the highest dose of psilocybin, and chances are that the study couldn’t show it was more effective than that because it was underpowered to detect it, and not because there is no difference (in other words, the sample size was not large enough for the difference between high-dose psilocybin and 5-MeO-DMT to reach statistical significance). Also bear in mind the key difference that the trip lasts under 20 minutes in total, meaning that even if the trip fails to produce full effects, you can still afford to try it again ten more times in the same time interval that it would have taken you to experience a full psilocybin trip. More so, it is important to point out that the dose of 5-MeO-DMT taken by the participants of this study is considered to be at the edge between “light” and “common” in PsychonautWiki’s entry on the drug*. Indeed, for many people the “breakthrough” tends to happen around 10mg, and I’ve heard of people using up to 30mg of it at a time. (Beware: if you ever try this – please don’t jump straight to a high dose, as this can cause serious trauma as a result.) Therefore, I think it is reasonable to expect that future studies will confirm what anecdotal data is currently screaming: that 5-MeO-DMT is more “powerful” and “mystical” in its effects than psilocybin, LSD, DMT, 2C-B, and all the rest.

But what this “power” and “mysticism” exactly amounts to still lacks clear and useful definitions. More so, is there any concrete reason why 5-MeO-DMT may be also superior at healing trauma relative to, eg. LSD or psilocybin? Technically, one could currently argue that since the presentation of “complete mystical states” is a mediating factor in whether psilocybin has long-lasting psychological benefits, that 5-MeO-DMT is more effective simply because it has a higher probability of causing this effect. But I would argue that the texture of 5-MeO-DMT peak experiences is different and not only just more intense, and that the way in which it is different matters for its therapeutic value.

To investigate this particular difference, we now move on to examining the phenomenological difference between 5-MeO-DMT and DMT.


5-MeO-DMT vs. N,N-DMT: The 9 Lenses

My experience is that a reasonable ~20% of people I talk to who have a long-standing interest in psychedelics have heard about 5-MeO-DMT’s special properties. However, only a much smaller percentage of people have actually tried it. At Qualia Computing we have talked about its exceptional phenomenological properties a number of times. Yet it remains that most readers who reach out have not themselves experienced it. Hence I have not really had access to quality trip reports in order to say anything meaningful about the way in which it is different from DMT.

Thankfully, I’ve recently interviewed someone who has a decent level of experience with 5-MeO-DMT (20+ trips), along with a significant level of experience with vaporized DMT (100+ trips), and is also acquainted with the combination (10+ trips with both substances at once).

Given the incredibly intense psychoactive effects of 5-MeO-DMT (both for good and bad), most people struggle to put into words anything meaningful about the state. That said, as it has been the case with a number of other states of consciousness (e.g. LSD, DMT, and MDMA) I feel compelled to try to offer a sane, rational, agnostic, and pragmatic description of its phenomenology. In particular, I think that 5-MeO-DMT’s unique trauma-healing potential really deserves a close look. I believe that it sheds light on a wide range of topics of interest such as neural annealing, the Symmetry Theory of Valence, and the pseudo-time arrow (video). With this in mind, I inquired with my interviewee about the differences between N,N-DMT and 5-MeO-DMT. Together, after a lengthy open-ended discussion, we found the following ways to compare them:

1. Space vs. Form

QRI - Art and Consciousness copy 33QRI - Art and Consciousness copy 29

One of the first things that stands out when you take DMT at even small doses is the way in which colors get intensified. This is a special case of a very generalizable effect: in fact, every perceptual feature you can point to is enhanced while on DMT, from the sharpness of edges and pointy things to the feeling of movement and rotation. The interviewee indeed said that a brain on DMT “becomes a powerful qualia machine“.

After trying 5-MeO-DMT for the first time, most people already familiar with DMT mention something along the lines of “I was surprised that I didn’t see many colors.” The visual component of five is rarely very colorful; if color appears, it is in the form of a golden or sometimes light faint magenta or green hue. For the most part, the visual component of the experience is black and/or white. At times, one can see rainbow halos, but like rare subatomic particles, on 5-MeO-DMT rainbow colors come in and out of the vacuum, as if somehow equivalent to it. The bulk of the visuals manifest in a dazzling sense of spaciousness, as if there was a cosmic paint called “transparent/translucent”. The space often feels immeasurable due to a lack of a reference frame from which to make a judgement in terms of known comparisons. But what inevitably stands out is that the space seems large, uniform, harmonious, smooth, and luminous. Somatic feelings blend with this space, and the uniformity and symmetry of it allows for energy to seamlessly move throughout it. It really is a remarkable effect, one which can easily give rise to the felt-sense of Open Individualism. Yet, despite the engrossingly engaging character of these feelings, there is very little narrative complexity in sight.

Who knew that empty space could be so much fun? That you could fit so much love and bliss in an (experiential) vacuum? More so, the more you are able to relax into it, the more you embrace the waves of equanimity, the more you allow the space to become perfectly smooth and seamless… the more blissful it all gets!**

2. Crystals and Quasi-Crystals

Here is an interesting thing – ultrasound has been used in order to bias the way in which water crystals form, and thus creating much more “cubical” water than is otherwise possible. More generally, the phenomenon of vibration affecting crystallization processes is worth considering as an explanatory framework. DMT comes with a particular vibe that some have identified as having a characteristic frequency somewhere between 20 and 30Hz, whereas 5-MeO-DMT’s vibe seems to be a notch higher, perhaps in the range of 30 to 40Hz. On these drugs, your attention is jittered back and forth at a certain frequency, and this affects your ability to focus on any given part of your experience. The specific jittering itself makes it harder and easier to construct and manipulate certain thought-forms over others.

Speculatively, this model says that the jittering of attention caused by 5-MeO-DMT and DMT give rise to crystal and quasi-crystal building blocks, respectively, for phenomenal objects in one’s experience.

Phenomenologically, it seems that the vibratory signature of DMT effects doesn’t wrap around your experience an integer number of times. Thus, what we will call, for lack of a better term, the qualia crystals that form while on DMT seem to be inherently unstable and alien to your normal way of cogitating. The fact that the vibrations don’t fit perfectly in one’s experiential field forces it to bend out of shape to accommodate such vibrations. The result is constant chaos – fluid instabilities as the core effect.

Spatial_KH_2D_vorticity

Kelvin–Helmholtz instability (source)

On the other hand, with 5-MeO-DMT, it’s as if the vibration activates parts of the field of experience in exactly the right way for them to blend, unite, and resonate with one another. The vibrations fit perfectly inside one’s experiential field, and allows it to relax into its own natural shape. And this allows for perfect crystals of awareness to peacefully grow, multiply, and synchronize.

It is of course surprising that a tiny difference in the frequency of the vibe could have such large effects in the way phenomenology crystallizes. But this is true for other systems. When one talks about the complexity of shapes in resonant systems, for instance, Lissajou curves can provide a helpful intuition pump: in Lissajou curves, merely changing one of the frequencies by a small relative amount can result in a huge difference between the pictures drawn. From a simple circle to a complex mesh.

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According to the interviewee, 5-MeO-DMT would neatly correspond to one of the simplest Lissajou curves above, while the DMT sensations would be better evoked by one of the meshy ones.

With that said, it is worth mentioning that 5-MeO-DMT is probably not hitting the right frequencies merely by chance. It’s probably more that it is activating a system whose attractor is self-correcting and results in the kind of symmetrical crystallization that gives rise to deep feelings of bliss.

3. Attachment to Existence and Non-Existence

5-MeO seems to point at a super general sense of “relaxation”. A meditation teacher, Ajahn Brahm, talking about jhanas said that his mantra to achieve states of deep concentration and peace was: “Relax… to the maaaaaaaxxxx…”.

And according to the interviewee, the thrust of 5-MeO is that it feels like your nervous system is paradoxically injected with a lot of energy and yet the vibe of this energy is that of total and complete- ultimate?- relaxation. But our body and mind are not used to relaxing deeply. The contrast between this energy and one’s usual neurotic state can itself produce a lot of dissonance and resistance. In most cases, this is transient and contained to the first couple of minutes of the experience, though in higher doses and with bad luck, it can also spiral out of control. On small and moderate doses the energetic vibe of “relax to the max” takes over one’s experiential center of mass and teaches the rest of your nervous system how to relax.

It vibrates your nervous system in just the right way that all of your tensions, and hidden knots, and internalized stresses, bubble up to the surface, and you have the chance to try to “unravel” all of that tension.

After taking it a couple of times, you get the very nice feeling of being OK with whatever happens. 5-MeO-DMT might be described as a drug that allows you to reduce “thirst, craving, desire” in a very generalized kind of way. In Buddhist terms, this would be to reduce “Taṇhā“, which comes in three different kinds: “kāma-taṇhā (craving for sensual pleasures), bhava-taṇhā (craving for existence), and vibhava-taṇhā (craving for non-existence).” While we are used to hearing religious figures and moralists talk about the importance of not experiencing cravings for sensual pleasure, popular culture still lacks legible myths about the craving for existence and non-existence. So it comes as a shock for someone who has never developed meditative introspective insight just how much of our suffering has the flavor of either craving for existence or non-existence. Dosing on 5-MeO-DMT gives you a glimpse for what a mind devoid of these more subtle forms of craving feels like.

DMT comes with a vibratory frenzy that directly causes a lot of knots and tiny stress points throughout your entire experiential field. And to a large extent, how the experience unfolds is the result of you trying to manage all of those knots and stress points to avoid having them accumulate and concentrate in painful ways. The effect of this is that DMT acutely increases attachment to existence and non-existence. You wonder “what am I in this world?” and then cling to it, along with an intense fear of losing yourself in the world of vibration. The fear is quite involuntary and primal. And because you are clinging to who or what you are, there is something that you can lose, and that contributes to the feeling that the stakes are very high.acacia-trees-grown-on-the-african-savannah-stock-video-footage-png-tree-savannah-1920_1080

On 5-MeO you look at a landscape- say a tree in a Savannah- and you can see it in the most Zen way you can possibly imagine (and I don’t mean cutting cats in half). You think: “there is neither someone nor nobody in there” and “it’s all just arising and passing of ephemera”.

On DMT you look at the same landscape and you feel: “Oh gosh, what AM I in here? Am I that rock over there? That rock seems threatened by erosion! Am I the tree? But what if something comes and eats the tree?” and so on.

On DMT you feel like you are one of many little beings in a vast ecosystem. On 5-MeO-DMT you step back and you “realize” that you are the entire ecosystem.

In turn, this may explain to some extent the fact that the content of DMT hallucinations is often filled with exotic beings. And almost always, these beings have hyper-specific ways of life, tastes, intentions, and beliefs. The realms you experience on DMT are all saturated with attachment to existence and non-existence, and the beings you interact with are no exception. In fact, they may be a manifestation of those intensified cravings! From the interviewee:

“I’ve taken DMT about 100 times and have encountered many different vibes and kinds of intelligences in those realms. I’d love to map out the possible narratives – there are so many! Loosely speaking, I’ve had many different encounters with intelligent beings: from blissfully angelic and benevolent to outright demonic. Most of the beings I’ve encountered are somewhere in-between, and for the most part, tend to have pretty dualistic mindsets.

There is this whole class of beings I’d identify as harlequins/jesters that just love to play tricks with perception (I’m sure that’s what Terrence McKenna was pointing at).

Then there are “artists” which have a particular style that they explore and can range from emotionally self-sufficient to aggressively in-your-face about their work. The “look at THIS and look at THIS and look at THIS!!” kind of stance, where you are not given enough time to process what they’ve already shown you before they thrust even more stuff into you, and then attach ‘cookies’ into your etheric body to track you in future trips so you “like” and “subscribe” to their “interdimensional channel” or something like that.

There’s also a lot of beings that seem to want to tell you that they are confident that God does not exist and that “everything is allowed”. And I’ve felt that they are really indifferent to morality, but still have powerful abilities and unique qualia of a more scientific bent.

I once also encountered what felt like a true sadistic demon that played some really nasty tricks on my perception, and filled me with “etheric bugs” and had hundreds of little minions to attack me in many unpleasant ways. That said, I blame this on the fact that I was sleep deprived when I took DMT that one time, and it’s never happened before or since. But that experience gave me a lot of respect for the drug.

I’ve also encountered realms where they actually do consciousness research as such, and are benevolent and into engineering paradises. I even asked one of them if they knew my favorite philosopher, and they said “yes, what a nice fellow – we hope he will be more widely known in the future. We just wished that he wasn’t so sad a lot of the time.”

I have found that my pre-existing mood is the single most important variable that determines the kind of intelligences I encounter. So I’d really like to someday try MDMA and DMT combined. I suspect those would be very angelic beings most of the time.

Interestingly, I feel that while DMT feels profoundly spiritual, to a large extent it is less “nondual” than most other psychedelics. A lot of beings I’ve encountered simply don’t seem to care about oneness at all. But on LSD, mushrooms, and of course 5-MeO-DMT, the Golden Rule seems to play a very central role in the experience. Those experiences are much more of a “teaching” than the wacky stuff one encounters in the DMT realms.

When you take 5-MeO-DMT and DMT at the same time, you can really feel the contrast between the dualistic “us vs. them” vibe that underlies DMT and the unitive sense that underlies 5-MeO-DMT. I’ve experimented with the combo and found it to be super informative. And usually, I realize that while DMT turns your brain into a high-octane “qualia machine”, 5-MeO is in fact much more peaceful and happy in a deeper sense. I’d like to understand both, but my preferred “home” would be for sure the 5-MeO realms.”

4. Underfitting vs. Overfitting

One interesting lens with which to make sense of the difference between people who are open to experience and people who are not is that of model complexity, which casts this difference in terms of the statistical concepts of underfitting and overfitting.

Having narrow views, simple explanations, and enduring preferences is very good when the world itself is either very simple or impossible to understand. But having complex views, multi-layered explanations, and flexible preferences is more adaptive than the alternative in a world that is both complex and can be understood with some effort.

Indeed, some speculation about the nature of sleep from the predictive coding paradigm of cognition is that dreaming is a process of model complexity reduction. The information that we accumulate over the span of a day is incorporated in an ad-hoc fashion while awake, and only properly integrated (and pruned) after a good night’s sleep. This at least provides the theoretical precedent for describing a specific state of consciousness in terms of its effects on model complexity. And here we would propose that as a very general effect profile, 5-MeO-DMT reduces model complexity while N,N-DMT increases it.

As a consequence, we would posit that people who take five a lot will converge towards compelling yet over-simplified models of realty, whereas people who use DMT a lot will converge to overly complex and unnecessarily detailed explanation for even the simplest of phenomena.1__7OPgojau8hkiPUiHoGK_w

Perhaps in the future people could be diagnosed as chronic overfitters and underfitters. In turn, these two drugs could be given by prescription, for the maladies of improper model selection practices:

N,N-DMT would be given to the sufferers of too much worldview simplicity. People like this believe that the world is dominated by the struggle between capitalism and communism. They think that there is a 50% chance that God almighty exists. They assign zero probability to unlikely events, such as lizard people power conspiracies. In people like this, DMT is a powerful mind enhancer capable of challenging cartoonishly simple background assumptions and introducing a healthy dose of skepticism in mainstream narratives.

5-MeO-DMT would instead be given to people who are overwhelmingly embroiled in complex interpretations of the nature of reality. Whether it is in the realm of conspiracy theories, religious cults, the biochemistry of aging, or any such hopelessly convoluted field of research, a little five will unscramble the mind of the compulsive overfitter. Thanks to the drug, the Bayesian puncture, the Occam’s cut, and the pragmatic so what coalesce into a decimating hit to the load-bearing hub-nodes that feed unfalsifiable belief systems. The model complexity reduction effect dissolves entire subfields, assimilates clusters, and seamlessly mends discontinuities in the reality mappings of the patient. At moderate dosages and treatment regimes, the sufferer recovers fully. The sufferer often ends up healed of their traumas, and occasionally healed of many more things than expected. At levels much above those of the therapeutic standard of care, there is a risk that the treatment may result in the healing of the fundamental traumas of conscious experience. The drug may offer the patient a chance to relinquish phenomenal reality in exchange for an extemporal “ultimate relief”. To extinguish the flame of existence, as they say.41592_2016_Article_BFnmeth3968_Fig1_HTML

Importantly, after 5-MeO-DMT therapy, the patient is, let’s say (for the sake of speculating), 20 times as likely as members of the general public to say yes to questions like “Are we all one consciousness?”, “Is the world a process created for the refinement of our souls?” and “Is the universe made of infinite consciousness?”.

So where does that leave us? The good news is that this may have game-theoretical benefits for the side of consciousness in the eternal battle between consciousness and pure replicators. The bad news is that it can overwrite important information obtained from the senses, one’s education, and logical reasoning:

Becoming the God of “I-AM-Now-ness” and filling your entire experiential field with that flavor of awakening is a recipe for ecstasy, not for good epistemology.

Indeed, the patient may become a bit hooked to the simplification of their model complexity; to make reality as they know be replaced by a simpler, yet more intense, version of perceived reality is very tempting. It can be seductive to embrace a view like “you are God and you have created everything for your own amusement” or “you are the dream of God”. Rather than compassion, why not indifference? Being the “way God entertains itself” is both poetically satisfying and super trippy. A lot of people would find that such belief adds some spice to their lives. Overfitting-and-underfitting-effect-on-error

But the price of truth is everything. In turn, it would be ideal to complement any model complexity reduction that goes too far with a healthy amount of prediction errors.

5. Fixed-Points and Limit Cycles vs. Chaotic Attractors

The brain contains many self-correcting feedback systems. Psychedelics in general can be modeled as drugs that mess with the inhibitory component of excitation-inhibition feedback systems. They accomplish this, quite possibly, by disrupting the inhibitory serotonergic connections coming from the cortex that gate the excitatory input coming from the thalamus. This may account for why tracers look the way they do – the failure to inhibit the thalamus results in looped replays of recent states. This may go a long way in explaining why people find “video feedback” so trippy and fascinating. Namely, because a lot of psychedelic effects can be understood as feedback getting out of control, literally.

oscillation_1_5_5_75_75_1_10_0-05_signal_trailing

More concretely, at the Harvard talk on the Hyperbolic Geometry of DMT experiences I introduced this notion that each DMT experience as a whole can be thought of as a trajectory in the energy vs. complexity landscape. Here, the vertical axis indicates the degree of energy of the experience (roughly corresponding to the intensity, brightness, and amount of qualia), while the horizontal axis represents how much information is encoded in the experience. One interesting operationalization of information is through the concept of symmetry breaking***, in which case the horizontal axis approximately tracks the “distance from perfectly symmetrical spaces in terms of number of symmetry breaking operations”.

I then postulated that we could generate an ontology based on feedback + noise to explain how two DMT trips of roughly the same level of intensity can nonetheless contain very different amounts of information.

Hyperbolic Geometry of DMT Experiences copy 50

What I did not mention at the time was that while DMT does have the ability to send you to any place in the energy-complexity landscape, most of the experiences are in the region of middle-complexity. In fact, especially strong DMT trips tend to become fully chaotic, so there is even a mild correlation between dosage and complexity. On the other hand, 5-MeO-DMT tends to propel you towards the low-complexity region of the space.

Using a feedback system ontology we could thus posit that 5-MeO-DMT modifies the feedback parameters of your brain in such a way that the states it gives rise to are ether fixed points or short limit cycles:

The video above depicts a fixed point (as with the other animations below, I took this from an old 1984 video about video feedback you can see here). A fixed point is a configuration of the system that is stable upon feedback iterations. In the video above we see a fixed point consisting of a cross (presumably the result of the camera having a 90 degree tilt) that is then perturbed and eventually collapses into just a single circular dot at the center.

The above are limit cycles. The first (left) is a comparatively simple limit cycle in that every stage along its reproduction cycle is very similar to each other. The second (right) one is a bit more complex, yet despite a long winded path, it really does repeat more or less perfectly over and over. 5-MeO-DMT limit cycles are more akin to the one on the left, but on occasion may be a bit more complex and rhythmic over the span of seconds. Either way, there is often a strong pull towards a simple resonant pattern with remarkable stability.

Contrast that with chaotic attractors:

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Chaotic pseudo-time arrow

When we have actual chaos, the states continue to change indefinitely. We could then posit that DMT’s characteristic jittering seems to prevent the formation of stable fixed points or short limit cycles. Despite both DMT and 5-MeO-DMT disrupting feedback in the brain, the subtle differences in the way parameters of this feedback are modified can make all the difference between perfectly simple and smooth results and the endless generation of chaotic structures.

6. Modulating Lateral Inhibition

Another exciting lens with which to look at the difference between these psychedelics is by allusion to lateral inhibition: according to a couple of recent trip reports I received from another anonymous source, there is a remarkable difference between the tracers of 5-MeO-DMT and those of DMT. In particular, the anonymous tripper points out that DMT tracers are chains of concatenated positive and negative after-images of the stimulation source, whereas 5-MeO-DMT only produces positive after-images.

afterimage (1)

Stare at the cross. The green ball you see as a result is the “negative after-image” of the missing purple dot. 

In other words, when you see a blue ball moving on a screen, on DMT you will see tracers of that ball that change in color from blue to yellow to blue again and so on, all following after the original blue ball. But on 5-MeO-DMT, one will only see a long blue tracer. This is a remarkable difference, and if true, it would seem to be an important hint.****

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Orientation selectivity map in the visual cortex

Lateral inhibition in the cortex prevents the overlapping of incompatible features in one’s own experience. For example, the primary visual cortex shows a map of orientation selectivity as shown above. Each hypercolumn is selective to only a specific orientation, and the surrounding hypercolumns are selective to different orientations. More so, via lateral inhibition, when a hypercolumn is activated, it inhibits the surrounding ones.

In this model, DMT would perhaps leave this process untouched, so that when the brain is massively energized, it still maintains this flip-flopping between each feature and its complement. Indeed, some people have described DMT as turning half of your neurons fully on, the other half of your neurons fully off, then inverting the activation so that the off neurons are turned on and the on ones are turned off, and flip-flopping between these two steps many times per second. Could this be the phenomenal expression of having energized checkerboard patterns of excitation and inhibition saturating your cortex? That is, taking a system with in-built lateral inhibition into over-drive?

5-MeO-DMT, on the contrary, seems to allow for “all colors to blend together into pure white light”, and “the past and the future to collapse into the present”, and the “self-other distinction to be dissolved”, and so on. Intuitively, if the drug is biochemically disabling lateral inhibition, that could be reflected as a profound sense of unity and interconnectedness at the phenomenological level, “transcending every last barrier”.

7. Diffuse Attention vs. Focused Attention

As we mentioned earlier, DMT tends to come with a feeling of “becoming tense” while 5-MeO-DMT has a primary vibe of “becoming relaxed”. One way in which we can model this is in the way the drugs influence whether your attention is focused or diffuse. Now, I should say that this model will be necessarily incomplete because at the peak of a 5-MeO experience one often does in fact feel super focused in some way. But I would posit that this sense of focus is much more holistic than the way our common-sense use of the term would suggest. The focus on DMT, on the other hand, does feel very much akin to the “conventional” sense of focus, where you are able to precisely position figure and ground in such a way that they have as much contrast as possible.dmt_from_scalable_locally_injective_maps

In a way, the beings one encounters on DMT could be thought of as “attentional attractors”. As you create a lot of little focal points during the experience, these begin to build up and define the contents of your mind. Each focal point makes it easier for you to create another one nearby. This snowballs into an effect where there are clusters of focal points that become the “centers of mass” of the narrative. These could very well be what underlies the “beings” on DMT. Using Buddhist terms again, DMT beings might perhaps be thought of as exotic “nimittas“: attention hubs.

Also, because the experience is high-dimensional and changes your sense of what “understanding” even means, it seems that the feeling of super-intelligence on DMT might be a projection of one’s own super-intelligence (of a certain kind) in the state.

In contrast, 5-MeO-DMT makes it easy to de-focus on anything. To let go, and experience it in a diffuse way.

8. Big Chunks and Tiny Chunks vs. A Power Law of Chunks

Geology uses the word matrix in way that is very different from either math or science fiction aficionados. In geology, a matrix is the entire mass of materials on a rock within which crystals, grains, and clasts are found. As Anders and Maggie discussed recently, the way in which minerals form depends to a large extent on the presence of water in the process of crystallization. The huge diversity of minerals we see on Earth’s surface is partly a result of the availability of water in the mantle. Perhaps a lens with which to see DMT is as playing the same role in the brain as water does in fractional crystallization. It lubricates the matrix of your mind, which enables the crystallization of countless qualia exotica. 5-MeO-DMT instead homogenizes the kinds of crystals that can form.

In brief, DMT is to 5-MeO-DMT as a matrix of diverse minerals is to a mono-phasic large enclave. DMT is like complex music (cf. music as an ordered phase of sound) while 5-MeO-DMT is like a single mantra repeated over and over. Is this metaphor useful? It seemed to resonate with the interviewee.

9. Integration vs. Fragmentation

In Neural Annealing, Mike Johnson argues that what makes MDMA special for healing trauma is what at QRI we call integration:

On MDMA’s strangely powerful therapeutic effects, I’d suggest MDMA shares the ‘basic psychedelic package’ with substances like LSD and psilocybin (albeit a little weaker at common doses). Anything with this ‘baseline’ package significantly increases the energy parameter of the brain, which both allows escape from bad local minima and canalizes the brain’s core CSHWs, which both should be highly therapeutic. My intuition is MDMA may also have a particular effect on stochastic firing frequencies of neurons, and that this effect essentially acts as an emergent metronome – and this metronome will drive synchronicity between diverse brain regions. Given the presence of such a region-spanning ‘clean’ metronomic signal, brain regions that have partially ‘stopped talking to each other’ will re-establish integration, and some of this integration will persist while sober (or rather, some of the reasons for the lack of integration will have been negotiated away during the MDMA-driven integration). Plausibly this ‘emergent metronome’ effect may also underlie the particular phenomenological effects of 5-MeO-DMT as well, particularly in terms of sense of unity, high valence, and therapeutic potential. (HT to Steve Lehar for pointing at this ’nystagmus’ phenomenon as being somehow linked to MDMA’s mood-lifting effect, and to Andrés for calling my attention to Lehar’s work and suggesting 5-MeO-DMT may also share this mechanism.)

Like most other psychedelics, N,N-DMT also shares the same ‘basic psychedelic package’ and can have beneficial therapeutic effects. But it lacks this ‘special’ ability that allows arbitrary parts of your nervous system to rhythmically entrain with one another. This “emergent metronome” on MDMA and 5-MeO-DMT works as a kind of universal “vibratory currency” and results in a reduction of inner dissonance to a much greater extent than (relatively) simple “energizers” like DMT.

To Wrap Up

We hope that the above discussion has given you an idea about the difference between DMT and 5-MeO-DMT and why this matters for their therapeutic potential. The above is just the start of a deep inquiry into the topic that will certainly take many years, but we believe that it is a novel way of seeing the contrast between these two substances that may be generative for others. We also believe that it is very worth trying: nailing down this difference may be incredibly important to develop novel ways of treating mental illness. While DMT will undoubtedly continue to dazzle and amaze people curious about the state-space of consciousness, the superlative potential of 5-MeO-DMT to heal trauma puts it on a different level of importance altogether.

In the future we shall also explain why MDMA and ketamine have this potential. And ultimately, as we begin to understand what makes these substances so special, we hope to find ways of creating effective therapies from first principles. Stay tuned.



* The toad venom dose was 50mg, with an estimated 5-7mg of 5-MeO-DMT. This is admittedly likely to produce somewhat more potent effects than just 5 to 7mg of pure 5-MeO-DMT. But the extent of this enhancement is currently poorly understood, and you can find many people online saying that the difference is tiny and others who argue it is enormous. Given just how intense and qualitatively unique pure 5-MeO-DMT already is, I think that applying Occam’s razor would tell us that “it’s just the 5-MeO-DMT itself”. So while I am ready to accept the possibility of profound synergy between other tryptamines in toad venom and 5-MeO, I am not holding my breath for it. I, rather, expect that the difference between 5-MeO alone and the full-spectrum stuff will be akin to the difference between drinking 10 shots of vodka and drinking 10 shots of vodka and one chamomile tea. Namely, a real but largely inconsequential difference.

** This, of course, blends well with the Symmetry Theory of Valence, a subject to which we shall return in the near future.

*** This is where information-less states are those which are perfectly symmetrical, and the information content of a state is defined as the minimum number of symmetry breaking operations needed to transform an information-less state into it.

**** This is admittedly very weak evidence so far. If you have experience with both of these compounds and have explored the way in which they give rise to after-images, please let me know if you can confirm or deny the effect here mentioned.


Picture: Andrés & Claudia Silva Ruiz

Mini-Series on Open Individualism

Part 1: Introduction

In this video I introduce the concept of Open Individualism- the idea that we are all one consciousness -, why it is relevant, and who has historically been a proponent of it (Hinduism, Einstein, Schopenhauer, Schrödinger, etc.).

We also cover the fact that there is a distinction between Open Individualism as an experience and Open Individualism as a philosophical position with rigorous arguments. I mention that I generally consider arguments to be more powerful and useful than just relying on first-person experiences, though experiences certainly have their place.

Part 2: Definitions

We define and illustrate:

  • Closed Individualism (“you are a separate observer that exists from moment to moment”)
  • Empty Individualism (“you are just a moment of experience”)
  • Open Individualism (“we are all one consciousness”)

Part 3: Strongest Arguments

In this video we provide some of the strongest arguments in favor of Open Individualism:

  • Based on continuity of identity from moment to moment.
  • Reductio ad absurdum of Closed Individualism.
    • Fission.
    • Fussion.
    • Lack of viable Identity Carriers (IC).
  • Based on parsimony.
  • Undecidability.
  • Self-locating uncertainty when taking a “view from nowhere”.

Part 4: Loneliness, Psychosis, Ecstasy

I address some key considerations when investigating Open Individualism:

  1. It is crucial to distinguish between our human feelings about a certain idea and the merits and drawbacks of that idea on its own.
  2. Open Individualism tends to cause a lot of bliss at first (caused by defanging death)
  3. But Open Individualism can often take a turn for the bad.
  4. It makes you realize that you won’t only not die, which is good, but also be forced to experience all of the suffering of the world (or multiverse).
  5. More so, it can make you feel “cosmically lonely” – a feeling typical of bad trips where the focus is the pursuit of oneness.
  6. While the increased sense of responsibility caused by Open Individualism is good, it is important not to be overwhelmed by the suffering of the world. As they say “one day at a time” and perhaps we could extend that advise to “one lifetime at a time”.
  7. The feeling of loneliness is likely the result of mixing deep brain circuits evolved to track things like one’s place in the tribe via feelings of belongingness and togetherness, which can get deactivated or over-activated when fully internalizing otherwise-neutral philosophical viewpoints. In other words, those feelings are reflections of our mammal brain’s response to Open Individualism rather than inherent to the philosophy in and of itself.

I also briefly mention the interesting relationship between the ways we represent the world and valence (i.e. the pleasure-pain axis). Given the Symmetry Theory of Valence, which claims that more “consonant and symmetrical” states of consciousness feel better, experiencing “unitive states of mind” usually comes with the “dissolution of internal boundaries”. Therefore, to actively simulate a world where we are all one is likely to come with very positive feelings (perhaps even orgasmic, and ecstatic). Yet, this is not intrinsic of oneness as such – rather, it’s an artifact of the way valence is implemented in the brain! Subtle, but key, distinction.

Finally, I also explain that “the highest truth” is not oneness:

In some sense, Open Individualism is “level 0” – it is the start of a journey of self-discovery. We still need to address things like how to eliminate extreme suffering, understand how physics describes fields of qualia, the binding problem, how causality interfaces with consciousness, what makes consciousness have an “arrow of time”, and so on. While oneness is a piece of the puzzle, it is by no means “the final answer”. To think otherwise leads to mental pathologies that constrict- rather than expand- one’s understanding and engagement with the world.

Part 5: Ethics, Coordination, Game Theory

In this video I discuss the beneficial implications of Open Individualism. Namely:

  1. Its ethical implications, where one feels a sense of responsibility for the wellbeing of all sentient beings.
  2. Its ability to solve coordination problems.
  3. Its game-theoretical effects.

I cover how a cultural, philosophical, and scientific movement that grounds the feelings of oneness and universal love in rigorous philosophy and science would be much more powerful and consequential than yet another attempt at a naïve spreading of “peace, love, and harmony”. Indeed, it is the philosophical strength of Open Individualism, rather than just its experiential component, that makes it viable as a tool for solving coordination problems.

In particular, I explain that studying 5-MeO-DMT and MDMA from a rigorous, scientific, and methodical point of view is one of the most promising ways of changing the world for the better. Creating reliable, sane, and integrative methods of experiencing oneness and universal love could help us transform weak feelings of altruism into a solid and powerful new conception of decision theoretic rationality.

We invite you to think with us about how to carry this out for the benefit of all sentient beings.

5-MeO-DMT Awakenings: From Naïve Realism to Symmetrical Enlightenment

In the following video Leo Gura from actualized.org talks about his 30-day 5-MeO-DMT streak experiment. In this post I’ll highlight some of the notable things he said and comment along the way using a QRI-lens to interpret his experiences (if you would rather make up your mind about what he says without my commentary just go and watch the video on your own before reading what I have to say about it).

TL;DR: Many of the core QRI paradigms such as Neural Annealing, the Symmetry Theory of Valence, the Tyranny of the Intentional Object, and Hyperbolic Geometry on Psychedelics have a surprising degree of explanatory power when it comes to making sense of the peculiar process that ensues when someone takes a lot of 5-MeO-DMT. The deep connections between symmetry, valence, smooth geometry, and information content are made clear in this context due to the extreme and purified nature of the states induced by the drug.


Introduction

Recently Adeptus Psychonautica (who has interviewed me in the past about the hyperbolic geometry of DMT experiences) put out a video titled “When you have taken too much – Actualized.org“. This video caught my attention because Leo Gura did something that is rather taboo in spiritual communities, and for good reasons. Namely, he tried to convince the viewers that he had achieved a level of awakening that nobody (or perhaps only a few people) on the entire planet had ever reached. He then said he was going to isolate for a month to integrate these profound awakenings and come back with a description of what they are all about.

Thankfully I didn’t have to wait a month to satisfy my curiosity and see what happened after his period of isolation because by the time I found about it he had already posted his post-retreat video. Well, it turns out that he used those 30 days of isolation to conduct a very hard-core psychedelic experiment. Namely, he took high doses of 5-MeO-DMT daily for the entire month. I’ve never heard of anyone doing this before.

Learning about what he experienced during that month is of special interest to me for many reasons. In particular, thanks to previous research about extreme bliss and suffering, we had determined that 5-MeO-DMT is currently the psychedelic drug that has the most powerful and intense effects on valence. Recall Logarithmic Scales of Pleasure and Pain (video): many lines of evidence point to the fact that extreme states of consciousness are surprisingly powerful in ways that are completely counterintuitive. So when Leo says that there are “many levels of awakening” and goes on to discuss how each level is unrecognizably more intense and deeper than the previous one, I am very much inclined to believe he is trying to convey a true property of his experiences. Note that Leo did not only indulge in psychedelics; we are talking about 5-MeO-DMT in particular, which is the thermonuclear bomb version of a psychoactive drug (as with Plutonium, this stuff is best handled with caution). More so, thankfully Leo is very eloquent, which is rare among people who have had many extreme experiences. So I was very eager to hear what he had to say.

While I can very easily believe his trip reports when it comes to their profundity, intensity, and extraordinary degree of consciousness, I do not particularly find his interpretations of these experiences convincing. As I go about describing his video, I will point out ways in which you can take as veridical his phenomenological descriptions without at the same time having to agree with his interpretations of them. More so, if you end up exploring these varieties of altered states yourself, by reading this you will now at least have two different and competing frameworks to explain your experiences. This, I think, is an improvement. Right now the psychedelic and scientific community has very few lenses with which to interpret something as extraordinary as 5-MeO-DMT experiences. And I believe this comes at a great cost to people’s sanity and epistemic rationality.

What Are Leo’s Background Assumptions?

In the pre-retreat video Leo says that his core teachings (and what he attempts to realize on his own self) are: (1) you are literally God, (2) there is nothing but consciousness – God is infinite consciousness, (3) everything is states of consciousness – everything at all times is a different state of consciousness, (4) you are love – and love is absolute – this is all constructed out of love – fear is just fear of aspects of yourself you have disconnected from, (5) you have no beginning and no end, (6) you should be radically open-minded. Then he also adds that physical and mental health issues are just manifestations of your resistance to realizing that you are God.

What Are My Background Assumptions?

Personal Identity

I am quite sympathetic to the idea of oneness, which is also talked about with terms like nonduality and monopsychism. In philosophical terminology, which I find to be more precise and rigorous, this concept goes by the name of Open Individualism – the belief that we are all one single consciousness. I have written extensively about Open Individualism in the past (e.g. 1, 2, 3), but I would like to point out that the arguments I’ve presented in favor of this view are not based on direct experience, but rather, on logical consistency from background assumptions we take for granted. For instance, if you assume that you are the same subject of experience you were a second ago, it follows that you can exist in two points in space-time and still be the same being. Your physical configuration is different than a few seconds ago (let alone a decade), you have slightly different memories, the neurons active are different, etc. For every property you point out as your “identity carrier” I can find a counter-example where such carrier changes a little while you still remain the same subject of experience. Add to that teleportation, fission, fusion, and gradual replacement thought experiments and you can build a framework where you can become any other arbitrary person without a loss of identity. These lines of argumentation coupled with the transitivity of identity can build the case that we are indeed all one to begin with.

But realize that rather than saying that you can grasp this (potential) truth directly from first person experience, I build from agreed upon assumptions to arrive at an otherwise outlandish view. Understanding the argument does not entail “feeling we are all one”, and neither does feeling we are all one entails understanding the arguments!

Indirect Realism About Perception

There is a mind-independent world out there and you never get to experience it directly. In some sense, we each live in a private skull-bound world-simulation that tracks the fitness-relevant features of our environment. Hence, during meditation, dreaming, or psychedelic states you are not accessing any sort of external reality directly, but rather, exploring possible configurations and qualities of your inner world-simulation. This is something that Leo may implicitly not realize. In particular, interpreting 5-MeO-DMT experiences through direct realism (also called naïve realism – the view that you experience the world directly through your senses) would make you think that you are literally merging with the entire cosmos on the drug. Whereas interpreting those experiences with indirect realism merely entails that your inner boundaries are dissolving. In other words, the partitions inside your world-simulation are what implements the feeling of the self-other duality. And since 5-MeO-DMT dissolves inner boundaries, it feels as though you are becoming one with your surroundings (and the rest of reality).

Physicalism and Panpsychism

An important background assumption is that the laws of physics accurately describe the behavior of the universe. This is distinct from materialism, which would also posit that all matter is inherently insentient. Physicalism merely says that the laws of physics describe the behavior of the physical, but leaves its intrinsic nature as an open question. Together with panpsychism, however, physicalism entails that what the laws of physics are describing is the behavior of consciousness.

Tyranny of the Intentional Object

We tend to believe that what makes us happy is external to us, while in reality happiness is a state of consciousness triggered by external circumstances. Our minds lead us to believe otherwise for evolutionary reasons.

Valence Structuralism

What makes an experience feel good or bad is not its semantic content, its computational use, or even whether the experience is self-reinforcing or not. What makes experiences feel good or bad is their structure. In particular, a very promising idea that will come up below is that highly symmetrical states of consciousness are inherently blissful, such as those we can access during orgasm, meditation, psychedelics, or even just good food and a hug. Recall that 5-MeO-DMT dissolves internal boundaries, and this is indicative of increased inner symmetry (where the boundaries themselves entail symmetry breaking operations). Thus, an exotic state of oneness is blissful not because you are merging with God, but “merely” because it has a higher degree of symmetry and therefore it’s valence is higher than what we can normally experience. In particular, the symmetry I’m talking abut here may be an objective feature of experiences perhaps even measurable with today’s neuroimaging technology.

There are additional key background philosophical assumptions, but the above are enough to get us started analyzing Leo’s 5-MeO-DMT journey from a different angle.


The Video

[Video descriptions are in italics whereas my commentary is bolded.]

For the first 8 minutes or so Leo explains that people do not really know that there are many levels of enlightenment. He starts out strong by claiming that he has reached levels of enlightenment that nobody (or perhaps just a few people) have ever reached. More so, while he agrees with the teachings of meditation masters of the past, he questions the levels of awakening that they had actually reached. It takes one to know one, and he claims that he’s seen things far beyond what previous teachers have talked about. More so, he argues that people simply have no way of knowing how enlightened their teachers are. People just trust books, gurus, teachers, religious leaders, etc. about whether they are “fully” enlightened, but how could they know for sure without reaching their level, and then surpassing them? He wraps up this part of the video by saying that the only viable path is to go all the way by yourself – to dismiss all the teachers, all the books, and all the instructions and see how far you can go on your own when genuinely pursuing truth by yourself.

With this epistemological caveat out of the way, Leo goes on to describe his methodology. Namely, he embarked on a quest of taking 5-MeO-DMT at increasing doses every day for 30 days in a row.leo_10_05

At 10:05 he says that within a week of this protocol he started reaching levels of awakening so elevated that he realized he had already surpassed every single spiritual teacher that he had ever heard of. He started writing a manifesto explaining this, claiming that even the most enlightened humans are not truly as awake as he became during that week. That it had became “completely transparent that most people who say they are awake or teach awakening are not even 1% awake”. But he decided not to go forward with the manifesto because he still values the teachings of spiritual leaders, whom according to him are doing a great service to mankind. He didn’t want to start, what he called, a “nonduality war” (which is of course a fascinating term if you think about it).

The main thing I’d like to comment here is that Leo is never entirely clear about what makes an “awakening experience” authentic. From what I gather (and from what comes next in the video) we can infer that the leading criteria consists of a fuzzy blend of experience of certainty, feeling of unity, and sense of direct knowing coupled together. To the extent that 5-MeO-DMT does all of these things to an extraordinary degree, we can take Leo on his words that he indeed experienced states of consciousness that feel like awakening that are most likely inaccessible to everyone who hasn’t gone through a protocol like his. What is still unclear is how exactly the semantic contents of these experiences are verified by means other than intuition. We will come back to that.

At 16:00 he makes the distinction between awakening as merely “cessation”, “nothingness”, “emptiness”, “the Self”, or that “you are nothing and everything” versus what he has been experiencing. He agrees that those are true and worthy realizations, but he claims that before his experiences, these understandings were still only realized at a very “low level”. Other masters, he claims, may care about ending suffering, about peace, about emptiness, and so on. But that nobody seems to truly care about understanding reality (because otherwise they would be doing what he’s doing). He rebukes possible critics (arguably of the Zen variety) who would say that “understanding is a function of the mind” so the goal shouldn’t be to understand. He asserts that no, based on his lived experience, that consciousness is capable of “infinite understanding”.

Notwithstanding the challenges posed by ultrafinitism, I am also inclined to believe Leo that he has experienced completely new varieties of “understanding”. In my model of the mind, understanding something means to have the ability to render it in your world-simulation in a particular kind of way that allows you to see it from every possible angle you have access to. On 5-MeO-DMT, as we will see to a greater extent below, a certain new set of projective operations get unlocked that allow you to render information from many, many more points of view at the same time. It is unclear whether this is possible with meditation alone (in personal communication, Daniel Ingram said yes) but it is certainly extraordinarily rare for even advanced meditators to be able to do this. So I am with Leo when it comes to describing “new kinds of understandings”. But perhaps I am not on board when it comes to claiming that the content of such understandings is an accurate rendering of the structure of reality.

At 18:30 Leo asserts that what happened to him is that over the course of the first week of his experiment he “completely understood reality, completely understood what God is”. God has no beginning and no end. He explains that normal human understanding sees situations from a single point of view (such as from the past to the future). But that actual infinite reality is from all sides at once: “When you are in full God consciousness, you look around the room, and you can see it from every single point of view, from an infinite number of angle and perspectives. You see that every part of the room generates and manufactures and creates every other part. […] Here when you are in God consciousness, you see it from every single possible dimension and angle. It’s not happening lilnearly, it’s all in the present now. And you can see it from every angle almost as though, if you take a watermelon and you do a cross-section with a giant knife, through that watermelon, and you keep doing cross-section, cross-section, cross-section in various different angles, eventually you’ll slice it up into an infinite number of perspectives. And then you’ll understand the entire watermelon as a sort of a whole. Whereas usually as humans what we do is we slice down that watermelon just right down the middle. And we just see that one cross-section.”

Now, this is extremely interesting. But first, it’s important to point out that here Leo might implicitly be reasoning about his experience through the lens of direct realism about perception. That is, that as he experiences this profound sense of understanding that encompasses every possible angle at once, he seems to believe that this is an understanding of his environment, of his future and past, and of reality as a whole. On the other hand, if you start out assuming indirect realism about perception, how you interpret this experience would be in terms of the instantiation of new exotic geometries of your own world-simulation. Here I must bring up the analysis of “regular” DMT (i.e. n,n-DMT) experiences through the lens of hyperbolic geometry. Indeed, regular DMT elevates the energy of your consciousness, which manifests in brighter colors, fast movement, intricate and detailed patterns, and as curved phenomenal space. We know this because of numerous trip reports from people well educated in advanced mathematics who claim that the visual symmetries one can experience on DMT (at doses above 10mg) have hyperbolic curvature (cf. hyperbolic orbifolds). It is also consistent with many other phenomena one can experience on DMT (see the Eli 5 for a quick summary). But you should keep in mind that this analysis never claims that you are experiencing directly a mind-independent “hyperspace”. Rather, the analysis focuses on how DMT modifies the geometric properties of your inner world-simulation.

Hyperbolic Geometry of DMT Experiences copy 47

Energy-complexity landscape on DMT

Hyperbolic Geometry of DMT Experiences copy 38

DMT trip progression

Intriguingly, our inner world-simulations work with projective geometry. In normal circumstances our world-simulations have a consistent set of projective points at infinity – they render the modal and amodal features of our experience in projective scenes that are globally consistent. But psychedelics can give rise to this phenomenon of “point-of-view-fragmentation“, where your experience becomes a patchwork of inconsistent projective renderings. So even on “regular” DMT you can get the profound feeling of “seeing something from multiple points of view at once”. Enhanced with hyperbolic geometry, this can cause the stark impression that you can explore “hyperspace” with a kind of “ultra-understanding”.

Looking beyond “regular” DMT, 5-MeO-DMT is yet more crazy than that. You see, even on DMT you get the feeling that you are restricted in the number of points of view from which you can see something at the same time. You can see it from many more points of view than normal, but it’s still restricted. But the extreme “smoothing” of experience that 5-MeO-DMT causes makes it so that you cannot distinguish one point of view from another. So they all blend together. Not only do you experience semantic content from “multiple points of view at once” as in DMT, but you can erase distinctions between points of view so that one’s sense of knowing arises involving a totally new kind of projective effect, in which you actually feel you can see something from “every point of view at once”. It feels that you have unlocked a kind of omniscience. This already happens on other psychedelics to a lesser extent (and in meditation, and even sober life to an even lesser extent, but still there), and it is a consequence of smoothing the geometry of your experience to such an extent that there are no symmetry-breaking imperfections “with which to orient a projective point”. I suspect that the higher “formless” jhanas of “boundless space” and “boundless consciousness” are hitting at this effect. And on 5-MeO-DMT this effect is pronounced. More so, because of the connection between symmetry and smoothness of space (cf. Geometry Through the Eyes of Felix Klein) when this happens you will also automatically be instantiating a high-dimensional group. And according to the Symmetry Theory of Valence, this ought to be extraordinarily blissful. And indeed it is.

This is, perhaps, partly what is going on in the experience that Leo is describing. Again, I am inclined to believe his description, but happy to dismiss his naïve interpretation.

indras_net

Indra’s Net

At 23:15 Leo describes how from his 5-MeO-DMT point of view he realized what “consciousness truly is”. And that is an “infinitely interconnected self-communicating field”. In normal everyday states of consciousness the different parts of your experience are “connected” but not “communicating.” But on 5-MeO, “as you become more conscious, what happens is that every point in space inter-connects with itself and starts to communicate with itself. This is a really profound, shocking, mystical experience. And it keeps getting cranked up more and more and more. You can call it omniscience, or telepathy. And it’s like the universal communication system gets turned on for the first time. Right now your conscious field is not in infinite communication with itself. It’s fragmented and divided. Such that you think I’m over here, you are over there, my computer is over here, your computer is over there…”. He explains that if we were to realize we are all one, we would then instantly be able to communicate between each other.

Here again we get extremely different interpretations of the phenomena Leo describes depending on whether you believe in direct or indirect realism about perception. As Leo implicitly assumes direct realism about perception, he interprets this effect as literally switching on an “universal communication system” between every points in reality, whereas the indirect realist interpretation would be that you have somehow interlocked the pieces of your conscious experience in such a way that they now act as an interconnected whole. This is something that indeed has been reported before, and at QRI we call this effect “network integration“. A simple way of encapsulating this phenomenon would be by saying that the cross-frequency coupling of your nervous system is massively increased so that there is seamless information and energy transfer between vibrations at different scales (to a much lesser extent MDMA also does this, but 5-MeO-DMT is the most powerful “integration aid” we know of). This sounds crazy but it really isn’t. After all, your nervous system is a network of oscillators. It stands to reason that you can change how they interact with one another by fine-tuning their connections and get as a result decoupling of vibrations (e.g. SSRIs), or coupling only between vibrations of a specific frequency (e.g. stimulants and depressants), or more coupling in general (e.g. psychedelics). In particular, 5-MeO-DMT does seem to cause a massively effective kind of fractal coupling, where every vibration can get in tune with every other vibration. And recall, since a lot of our inner world simulation is about representing “external reality”, this effect can give rise to the feeling that you can now instantly communicate with other parts of reality as a whole. This, from my point of view, is merely misinterpreting the experience by imagining that you have direct access to your surroundings.

At 34:52 Leo explains that you just need 5-MeO-DMT to experience these awakenings. And yet, he also claims that everything in reality is imaginary. It is all something that you, as God, are imagining because “you need a story to deny that you are infinite consciousness.” Even though the neurotransmitters are imaginary, you still need to modify them in order to have this experience: “I’m talking about superhuman levels of consciousness. These are not levels of consciousness that you can access sober. You need to literally upgrade the neurotransmitters in your imaginary brain. And yes, your brain is still imaginary, and those neurotransmitters are imaginary. But you still need to upgrade them nevertheless in order to access some of the things I say.”

Needless to say, it’s bizarre that you would need imaginary neurotransmitter-mimicking molecules in your brain in order to realize that all of reality is your own imagination. When you dream, do you need to find a specific drug inside your dream in order to wake up from the dream? Perhaps this view can indeed be steel-manned, but the odds seem stacked against it.

At 38:30 he starts talking about his pornography collection. He assembles nude images of women, not only to relieve horniness, but also as a kind of pursuit of aesthetics. Pictures of nude super-models are some of the most beautiful things a (straight) man can see. He brings this up in order to talk about how he then at some point started exploring watching these pictures on 5-MeO-DMT. Recollecting this brings him to tears because of how beautiful the experiences were. He states “you’ve never really seen porn until you’ve seen it on 5-MeO-DMT.” He claims that he started to feel that this way he really felt that it is you (God) that is beautiful, which is manifested through those pictures.

A robust finding in the psychology of sexual attraction is that symmetry in faces is correlated with attractiveness. Indeed, more regular faces tend to be perceived as more beautiful. Amazingly, you can play with this effect by decorating someone’s face with face-paint. The more symmetrical the pattern, the more beautiful the face looks (and vice-versa). Arguably, the effect Leo is describing where people who are already beautiful become unbelievably pretty on 5-MeO-DMT involves embedding high-dimensional symmetries into the way you render them in your world-simulation. A lesser, and perhaps more reliable, version of this effect happens when you look at people on MDMA. They look way more attractive than what they look like sober.

Leo then brings up (~41:30) that he started to take 5-MeO-DMT on warm baths as well, which he reassures us is not as dangerous as it sounds (not enough water to drown if he experiences a whiteout). [It’s important to mention that people have died by taking ketamine on bath tubs; although a different drug, it is arguably still extremely dangerous to take 5-MeO-DMT alone on a bathtub; don’t do it]. He then has an incredible awakening surrendering to God consciousness in the bathtub, on 5-MeO-DMT, jerking off to beautiful women in the screen of his laptop. He gets a profound insight into the very “nature of desire”. He explains that it is very difficult to recognize the true nature of desire while on a normal level of consciousness because our desires are biased and fragmented. When “your consciousness becomes infinite” those biases dissolve, and you experience desire in its pure form. Which according to his direct experience turned out to be “desire for God, desire for myself”. And this is because you are, deep down “infinite love”. When you desire a husband, or sex, or whatever, you are really desiring God in disguise. But the problem is that since your path to God is constrained by the form you desire, your connection to God is not stable. But once you have this experience of complete understanding of what desire is, you finally get your desire fully quenched by experiencing God’s love.

This is a very deep point. It is related to what I’ve sometimes called the “most important philosophical question“, which is: is valence a spiritual phenomenon or spirituality a valence phenomenon? In other words, do we find experiences of God blissful because they have harmony and symmetry, or perhaps is it the other way around, where even the most trivial of pleasures, like drinking a good smoothy, feels good because it temporarily “gets you closer to God”? I lean towards the former, and that in fact mystical experiences are so beautiful because they are indeed extremely harmonious and resonant states of consciousness, and not because they take you closer to God. But I know very smart people who can’t decide between these views. For example, my friend Stuart Garvagh writes: 

What if the two options are indistinguishable? Suppose valence is a measure of the harmony/symmetry of the object of consciousness, and the experience of “Oneness” or Cosmic Consciousness is equivalent to having the object of consciousness be all of creation (God‘s object), a highly symmetrical, full-spectrum object (full of bliss, light, love, beingness, all-knowledge, empty of discernible content or information). All objects of consciousness are distortions (or refractions, or something) of this one object. Happiness is equivalent to reducing or “polishing-out” these distortions. Thus, what appears to be just the fact of certain states being more pleasant than others is equivalent to certain states being closer to God‘s creation as a whole. Obviously this is all pure speculation and just a story to illustrate a point, but I could see it being very tough to tease apart the truth-value of 1 and 2. Note: I’m fairly agnostic myself, but lean towards 2 (bliss is the perfume of “God realizing God” or the subject of experience knowing Itself). I would very much love to have this question answered convincingly!

At 50:00 Leo says that “everything I’ve described so far is really a prelude to the real heart of awakening, which is the discovery of love. […] I had already awakened to love a number of times, but this was deeper. By the two week mark the love really started to crack open. Infinite self-love. You are drowning on this love.” He goes on to describe how at this point he was developing a form of telepathy that allowed him to communicate with God directly (which is, of course, a way of talking to himself as he is God already). It’s just a helpful way to further develop. And what God was showing him was how to receive self-love. It was so much at first he couldn’t handle it. And so he went through a self-purification process.

An interesting lens with which to interpret this experience of purification is that of neural annealing. Each 5-MeO-DMT experience would be making Leo’s nervous system resonate in ways in new ways, slowly writing over previous patterns and entraining the characteristic high-symmetry patterns of the state. Over time, the nervous system adjusts its weights in order to be able to handle that resonance without getting its patterns over-written. In other words, Leo has been transforming his nervous system into a kind of high-valence machine, which is of course very beneficial for intrinsic feelings of wellbeing (though perhaps detrimental to one’s epistemology).

55:00: He points out that unlike addictive drugs, he actually had to push himself very hard to continue to take 5-MeO-DMT everyday for 30 days. He stopped wanting to do it. The ego didn’t want it. And yes, it was pleasurable once he surrendered on every session, but it was difficult, heavy spiritual work. He says that he could only really do this because of years of practice with and without psychedelics, intense meditation, and a lot of personal development. And because of this, he explains his 5-MeO experiences felt like “years of spiritual work condensed into a single hour.” He then says that God will never judge you, and will help you to accept whatever terrible things you’ve done. And many of his subsequent trips were centered around self-acceptance. 

Following the path of progressive neural annealing, going deeper and deeper into a state of self-acceptance can be understood as a deeper harmonization of your nervous system with itself.

At 1:01:20, Leo claims to have figured out what the purpose of reality truly is: “Reality is a contest for who can love who more. That’s really what life is about when you are fully conscious. […] Consciousness is a race for who can love who more. […] An intelligent fully conscious consciousness would only be interested in love. It wouldn’t be interested in anything else. Because everything else is inferior. […] Everything else is just utter silliness!”

I tend to agree with this, though perhaps not in an agentive way. As David Pearce says: “the pleasure-pain axis discloses the universe’s intrinsic value function.” So when you’ve annealed extremely harmonious patterns and do not get distracted by negative emotion, naturally, all there is left to do is maximize love. Unless we mess up, this is the only good final destiny for the cosmos (albeit perhaps it might take the form of a Hedonium shockwave, which at least in our current human form, sound utterly unappealing to most people).

1:06:10 “[God’s love] sparks you to also want to love it back. You see, it turns into a reciprocal reaction, where it is like two mirrors that are mirroring light between each other like a laser beam that is bouncing between two mirrors. And it’s bouncing back and forth and back and forth. And as it bounces back and forth it becomes more and more concentrated. And it strengthens. And it becomes more coherent. And so that’s what started happening. At first it started out as just a little game. Like ‘I love you, I love you, I love you’. A little game. It sounds like it’s almost like childish. And it sort of was. But then it morphed from being this childish thing, into being this serious existential business. This turned into the work. This was the true awakening. Is that with the two mirrors, you know, first it took a little while to get the two mirrors aligned. Because you know if the two mirrors are not perfectly aligned, the laser beam will kind of bounce back and forth in different directions. It’s not going to really concentrate. So that was happening at first. […] The love started bouncing back and forth between us, and getting stronger and stronger. […] Each time it bounces back to me it transforms me. It opens me up deeper. And as it opens me up deeper it reveals blockages and obstacles to my capacity to love.”

Now this is a fascinating account. And while Leo interprets it in a completely mystical way, the description also fits very well an annealing process where the nervous system gets more and more fine-tuned in order to be able to contain high levels of coherent energy via symmetry. Again, this would be extremely high-valence as a consequence of the Symmetry Theory of Valence. Notice that we’ve talked about this phenomenon of “infinite mirrors” on psychedelics since 2016 (see: Algorithmic Reduction of Psychedelic States).

At ~1:09:30 he starts discussing that at this point he was confronted by God about whether he was willing to love the holocaust, and rape, and murder, and bullies, and people of all sorts, even devil worshipers. 

Two important points here. First, it is a bit ambiguous whether Leo here is using the word “love” in the sense of “enjoyment” or in the sense of “loving-kindness and compassion”. The former would be disturbing while the latter would be admirable. I suppose he was talking about the latter, in which case “loving rape” would refer to “being able to accept and forgive those who rape” which indeed sounds very Godly. This radical move is explored in metta (loving-kindness) meditation and it seems healthy on the whole. And second: Why? Why go through the trouble of embracing all the evil and repulsive aspects of ourselves? One interpretation here, coming back to the analysis based on neural annealing, is that any little kink or imperfection caused by negative emotion in our nervous system will create slight symmetry breaking effects on the resonance of the entire system as whole. So after you’ve “polished and aligned the mirrors for long enough” the tiny imperfections become the next natural blockage to overcome in order to maximize the preservation of coherent energy via symmetry.

~1:12:00 Leo explains that the hardest thing to love is your own self-hatred. In the bouncing off of the love between you and God, with each bounce, you find that the parts you hate about yourself reflect an imperfect love. But God loves all of you including your self-hatred. So he pings you about that. And once you can accept it, that’s what truly changes you. “Because when you feel that love, and you feel how accepting it is, and how forgiving it is of all of your evil and of all of your sins… that’s the thing that kills you, that transforms you. That’s what breaks your heart, wide open. That’s what gets you to surrender. That’s what humbles you. That’s what heals you.” Leo then explains that he discovered what “healing is”. And it is “truth and love”. That in order to heal anyone, you need to love them and accept them. Not via sappy postcards and white lies but by truth. He also states that all physical, mental, and spiritual ailments have, at their root, lack of love.

If love is one of the cleanest expressions of high-valence symmetry and resonance, we can certainly expect that inundating a nervous system with it will smooth and clean its blockages, i.e. the sources of neural dissonance. Hence the incredible power of MDMA on healing nervous systems in the short-term. Indeed, positive emotion is itself healing and enhances neural coherence. But where I think this view is incomplete is in diagnosing the terrible suffering that goes on in the world in terms of a lack of love. For instance, are cluster headaches really just the result of lack of self-love? In here must bring back the background assumption of physicalism and make a firm statement that if we fall into illusion about the nature of reality we risk not saving people (and sentient beings more generally) who are really in the depth of Hell. Just loving them without taking the causally-relevant physical action to prevent their suffering is, in my opinion, not true love. Hence the importance of maintaining a high level of epistemic rigor: for the sake of others. (See: Hell Must Be Destroyed).

1:22:30 Leo explains that in this “love contest” with God of bouncing off love through parallel mirrors the love became so deep that for the first time in his life he felt the need to apologize: “I’m sorry for not loving more.” He goes into a sermon about how we are petty, and selfish, etc. and how God loves us anyway. “Real love means: I really love you as you are. And I don’t need anything from you. And especially all those things that you think I want you to change about you, I don’t need you to change. I can accept them all exactly as they are. Because that’s love. And when you realize THAT, that’s what transforms you. It is not that God says that he loves you. He is demonstrating it. It’s the demonstration that transforms you.” Leo expresses that he was then for the first time in his life able to say “thank you” sincerely. Specifically, “thank you for your love”: “This is the point at which you’ve really been touched by God’s love. And at this point you realize that that’s it, that’s the point, that’s the lesson in life. That’s my only job. It’s to love.” And finally, that for the first time in his life he was able to say “I love you” and truly mean it. “And you fall in love with God… but it doesn’t end there.”

An interesting interpretation of the felt-sense of “truly meaning” words like “I’m sorry”, “thank you”, and “I love you” is that at this point Leo has really deeply annealed his nervous system into a vessel for coherent energy. In other words, at this point he is saying and meaning those words through the whole of his nervous system, rather than them coming from a fragmented region of a complex set of competing internal family systems in a scattered way. Which is, of course, the way it usually goes.

1:35:30 Leo explains that at this point he started going into the stage of being able to radiate love. That he was unable to radiate love before. “I love that you are not capable of love. I love that. And when that hits you, that’s what fills you with enough love to overcome your resistance to love that next level thing that you couldn’t love.” Then at ~ 1:38:00 it gets really serious. Leo explains that so far he was just loving and accepting past events and people. But he was then asked by God whether he would be willing to live through the worst things that have happened and will happen. To incarnate and be tortured, among many other horrible things. And that’s what true love really means. “When you see a murder on the TV, you have to realize that God lived through that. And the only reason he lived through that is because it loved it.”

I do not understand this. Here is where the distinction between the two kinds of senses of the word “love” become very important. I worry that Leo has annealed to the version of love with the meaning of “enjoyment” rather than “loving-kindness and compassion”. Because a loving God would be happy to take the place of someone who went through Hell. But would a loving God send himself to Hell if nobody had to in the first place? That would just create suffering out of nothing. So I am confused about why Leo would believe this to be the case. It’s quite possible that there are many maxima of symmetry in the nervous system you can achieve with 5-MeO-DMT, and some of them are loving in the sense of compassionate and others are crazy and would be willing to create suffering out of nothing from a misguided understanding of what love is supposed to be. Again, handle Plutonium with caution.

1:43:00 Leo started wondering “what is reality then?” And the answer was: “It’s infinite consciousness. Infinite formless consciousness. So what happens was that my mind in my visual field as I was in that bathtub. My mind and my visual field focused in on empty space, and I sort of zoomed into that empty space and realized that that empty space is just love”. He then describes a process where his consciousness became more and more concentrated and absorbed into space, each dot of consciousness branching out into more and more dots of consciousness, turning into the brightest possible white light. But when he inquired into what was that white light he kept seeing that there was no end to it, and rather, that each point was always connected to more points. Inquiring further, he would get the response that at the core, reality is pure love. That it wouldn’t be and couldn’t be any other way.

The description sounds remarkably close to the formless jhanas such as “boundless space” and “boundless consciousness”. The description itself is extremely reminiscent of an annealing process, reaching a highly energized state of consciousness nearly devoid of information content and nearly perfectly symmetrical. The fact that at this incredibly annealed level he felt so much love supports the Symmetry Theory of Valence.

147:28 – And after Leo realizes that “Of course it is love!” he says that’s when the fear comes: “Because then what you realize is that this is the end. This is the end of your life. You are dead. If you go any further you are dead. Everything will disappear. Your family, your friends, you parents, all of it is completely imaginary. And if you stop imagining it right now, it will all end. If you go any further into this Singularity, you will become pure, formless, infinite, love for ever, loving itself forever. And the entire universe will be destroyed as if it never existed. Complete nothingness. Complete everythingness. You will merge into everyone.”

This sounds like the transition between the 6th and 7th Jhana, i.e. between “boundless consciousness” and “nothingness”. Again, this would be the result of further loss of information via an annealing process, refining the symmetry up to that of a “point”. Interestingly, Mike Johnson in Principia Quallia points out that as symmetry approaches an asymptote of perfection you do get a higher quality of valence but at the cost of reduced consciousness. This might explain why you go from “the brightest possible love” to a feeling of nothingness at this critical transition.

1:48:25: “…You will merge into everyone. Your mother, your father, your children, your spouse, Hitler, terrorists, 9/11, Donald Trump, rape, murder, torture, everything will become pure infinite love, merging completely into itself, there will be no distinction between absolutely anything, and that will be the end. And you will realize what reality is. Infinite consciousness. Love. God. And you will realize that everything in your life from your birth to this point has just been some imaginary story. A dream that was design to lead you to pure absolute infinite love. And you will rest in that love forever. Forever falling in love with yourself. Forever making love to yourself. Forever in infinite union. With every possible object that could ever exist. Pure absolute, omnipotent, omniscient, perfect, intelligent, consciousness. Everything that could ever possibly be, is you. And THAT is awakening. When you are this awake, you are dead. And you have no desire for life. There is no physical existence. There is no universe. Nothing remains. Your parents, and your spouse, and your children, they don’t stay back and keep living their lives, enjoying their life without you while your body drops dead. No, no, no, no, no. This is much more serious than that. If you do this. If you become infinite love, you will take everybody with you. There will not be anybody left. You will destroy the entire universe. Every single sentient being will become you. They will have no existence whatsoever. Zero. They will die with you. They will all awaken with you. It’s infinite awakening. It’s completely absolute. There will not be anything left. You will take the entire universe with you. Into pure oneness. THAT’S awakening.”

This is not the first time I hear about this kind of experience. It certainly sounds extraordinarily scary. Though perhaps a negative utilitarian would find it to be the ultimate relief and the best of all possible imaginable outcomes. With the human survival instinct, and quite possibly a body fully aroused with the incredible power of 5-MeO-DMT, this is bound to be one of the most terrifying feelings possible. It’s quite likely that it may be one element of what makes “bad 5-MeO-DMT experiences” so terrifying. But here we must recall that the map is not the territory. And while an annealing process might slowly write over every single facet of one’s model of reality and in turn making them part of a super-cluster of high-dimensional resonance that reflects itself seemingly infinitely, doing this does not entail that you are in fact about to destroy the universe. Though, admittedly, it will surely feel that way. Additionally, I would gather that were it possible to actually end the universe this way, somebody, somewhere, in some reality or another, would have already done so. Remember that if God could be killed, it’d be dead already.

1:52:01: “And I didn’t go there! As you can tell, since I’m still sitting here. I’m not there. I was too afraid to go there. And God was fine with it. It didn’t push me. But that’s not the end of the story! It’s still just the beginning.” He then goes on to explain that a part of him wanted to do it and another part of him didn’t want to. He says it got really loopy and weird; this really shook him. That God was beckoning him to go and be one forever, but he was still ambivalent and needed some time to think about it. He knew it would make no difference, but he still decided to ‘make preparations’ and tell his family and friends that he loves them before moving forward with a final decision to annihilate the universe. By the time he had done that… he had stopped taking 5-MeO-DMT: “The experiences had gotten so profound and so deep… this was roughly the 25th or 27th day of this whole 30 day process. I swore off 5-MeO-DMT and said ‘Ok I’m not doing any more of this shit. It’s enough'”. He explains that by this time the drug was making him feel infinite consciousness when waking up (from sleep) the next day. He felt the Singularity was sucking him into it. It felt both terrifying and irresistible. Every time he would go to sleep it would suck him in really strongly, and he kept resisting it. He would wake up sweaty and in a panic. He was tripping deeper in his sleep than in the bathtub. He couldn’t sleep without this happening, and it kept happening for about 5 days. “I just want to get back to normal. This is getting freaky now.” 

I’ve heard this from more than a couple people. That is, that when one does 5-MeO-DMT enough times, and especially within a short enough period of time, the “realizations” start to also happen during sleep in an involuntarily way. One can interpret this as the annealing process of 5-MeO-DMT now latching on to sleep (itself a natural annealing process meant to lessen the technical debt of the nervous system). Even just a couple strong trips can really change what sleep feels like for many days. I can’t imagine just how intense it must have been for Leo after 25 days straight of using this drug.

2:01:40 – Leo explains that when he was dozing off with a blanket on his living room (terrified of sleeping on his bed due to the effect just described) he experienced a “yet deeper awakening” which involved realizing that all of his previous awakenings were just like points and that the new one was like a line connecting many points. “Everything I’ve said up to this point were just a single dimension of awakening. And then what I broke through to is a second dimension. A second dimension of awakening opened up. This second dimension is completely unimaginable, completely indescribable, cannot be talked about, cannot be thought about. And yet it’s there. In it, are things that are completely outside of the physical universe that you cannot conceive or imagine.” He goes on to explain that there are then also a third, fourth, fifth, etc. dimensions. And that he believes there is an infinite number of them. He barely even began to explore the second dimension of awakening, but he realized that it goes forever. It kept happening, he had intense emotional distress and mood swings. But gradually after five more days it subsided, and he started to be able to sleep more normally. “And I’ve been working to make sense of all of this for the last couple of weeks. So that’s what happened.”

Alright, this is out of my depth and I do not have an interpretation of what this “second dimension of awakening” is about. If anyone has any clue, please leave a comment or shoot me an email. I’m as as confused as Leo is about this.

~2:05:00 – Leo confesses he does not know what would happen if he went through with joining the Singularity and mentions that it sounds a bit like Mahasamādhi. He simply has not answers at this point, but he asserts that the experience has made him question the extent of the enlightenment of other teachers. It also has made him more loving. But still, he feels frustration: “I don’t know what to do from here.”

And neither do I. Do you, dear reader?

Postscript: In the last 10 minutes of the video Leo shares a heart warming message about how reality is, deep down, truly, “just love” and that him saying this may be a seed that will blossom into you finding this out for yourself at some point in the future. He ends by cautioning his audience to not believe as a matter of fact that this is the path for everyone. He suggests that others should just use his examples from his own journey as examples rather than an absolute guide or how-to for enlightenment. He asks his audience to make sure to question the depth of their own awakening – to not believe that they have reached the ultimate level. He admits he has no idea whether there is an ultimate level or not, and that he still has some healing to do on himself. He remains dissatisfied with his understanding of reality.


Thank you for reading!

THE END

Making Amazing Recreational Drug Cocktails

Californidine

Imagine that you were tasked with creating a molecule to represent the spirit of California. I think that I would just glue together two MDMA molecules and call it a day.

1200px-Californidine.svg

Californidine

It turns out Californidine is indeed a real molecule, named after the California Poppy. I am still wrapping my head around the fact that Californidine can be described as two MDMA molecules sharing the nitrogen atom and with the end of the carbon chain of each MDMA molecule bonded at the 2-position of the benzene ring of the other one (minus a hydrogen atom). Interestingly, this compound has no psychedelic or empathogenic action. At best, it can be described as a very mild and unreliable relaxing agent of “herbal strength” akin to the active ingredients of chamomile, valerian, or ashwagandha. So, joining two powerful heart-openers gives rise to a mild sleep-inducer? Perhaps this is a metaphor for something.

californidine_mdma_

Californidine and MDMA

But that’s not what I want to talk to you about today. While gluing together psychoactive molecules may not have a (cartoonishly) desirable additive effect, doing so does express the spirit of what I want to propose today. And that is the impulse to use a creative and fun approach to drug design, letting your imagination run wild to avoid prematurely discarding one’s crazy ideas.

Notable Leads for Great Drug Combos

Over the last 10 years I’ve read many (many!) trip reports and have talked to hundreds of experienced psychonauts (see also: r/replications). It is largely thanks to a subset of these psychonauts, which for lack of a better term could be described as the subset of rational psychonauts, that I’ve been able to assemble empirically testable models for psychedelic phenomenology (some examples: Algorithmic Reduction of Psychedelic States, Hyperbolic Geometry of DMT Experiences, Quantifying Bliss, How to Secretly Communicate with People on LSD, etc.). Although my focus has largely been on the effects of individual drugs, I’ve become very cognizant of the fact that drug combinations can produce effects not accessible with individual substances. In other words, when it comes to mixing psychoactive substances, the sum is more often than not different from the sum of its parts. Some of these effects seem extremely significant both from a scientific and a philosophical point of view.

But first, an important disclaimer: mixing drugs is dangerous and you should never do it unless you really know what you are doing. The pile of celebrity deaths caused by multiple drug intoxication is only scratching the surface. Indeed, there are many combinations of drugs that are deadly even when the individual drugs taken on their own are relatively safe. For example, while 5-MeO-DMT is relatively safe when vaporized (save for egregiously negligent uses of the drug and the occasional drowning in one’s own vomit), taking 5-MeO-DMT orally in combination with an MAOI leads to extremely toxic reactions, such as severe hypertensive symptoms, overheating, and serotonin syndrome. Don’t do it. As a very rough guide for how mixtures of psychoactives behave, study the chart below.

Combo_2

Welcome to the practice of combining drugs. You may die. (source)

That said, just as drug combinations have a dangerous side, they also likely harbor hidden gems that are very safe, enjoyable, and mind-expanding in ways inaccessible via single drugs. As a general overview, some examples of the possible benefits of drug combinations include: (1) Enhanced euphoria, e.g. see speedball which is massively euphoric but also very dangerous, (2) reduced psychological discomfort (e.g. anxiolytics with psychedelics), (3) uniquely interesting effects, e.g. LSD + MDMA (see below), and (4) reduced physical side-effects and medical risks, e.g. calcium blockers to reduce MDMA neurotoxicity, 5HT2B antagonists to reduce cardiotoxicity of psychedelics, etc. as we’ll discuss. In addition, it is worth mentioning that from a therapeutic point of view, we also have the “more dakka effect“, where some conditions only respond to combining enough drugs (e.g. oncology). It’s possible chronic pain or severe depression may legitimately require multiple drugs to be adequately dealt with. Now let us examine in more detail some particularly interesting categories of drug combinations:

Psychedelics + Anxiolytics: According to many reports, phenibut in small doses seems to significantly reduce the anxiety that comes up on psychedelics. I am ambivalent about sharing this information given the fact that phenibut can become a huge problem for some people, but I think that on the whole it is wise for people to know that an over-the-counter “nootropic” can actually help avoid fear, discomfort, and panic attacks during a psychedelic experience.

Cannabis + Psychedelics: I generally find two kinds of psychedelic drug users. Those who cannot think of having a psychedelic trip without at some point smoking a joint, vaping, or eating a cannabis edible. And then those who would never dare to combine the two because they once had a terrifying experience with the combo. Interestingly, some of the people I’ve met over the years who seem to be able to easily handle massive doses of psychedelics (e.g. 500 micrograms of acid) respond terribly to weed, and especially badly if they are already tripping. Cannabis both modifies and potentiates psychedelic states of mind. It has a tendency to make the experience more conceptual rather than sensory or mystical. The combination also greatly increases the probability of getting stuck in time loops.

Empathogens + Psychedelics: One of the best descriptions of MDMA + LSD (also called candy-flipping) that I’ve found comes from Steven Lehar (emphasis added):

Under LSD and ecstasy I could see the flickering blur of visual generation most clearly. And I saw peculiar ornamental artifacts on all perceived objects, like a Fourier representation with the higher harmonics chopped off. LSD by itself creates sharply detailed ornamental artifactslike a transparent overlay of an ornamental lattice or filigree pattern superimposed on the visual scene, especially in darkness. Ecstasy smooths out those sharp edges and blurs them into a creamy smooth rolling experience. I would sometimes feel some part of my world suddenly bulging out to greater magnification, like a fish-eye lens distortion appearing randomly in space, stretching everything in that portion of space like a reflection in a funhouse mirror.

– Steven Lehar (The Phenomenal Character of LSD + MDMA)

Not everyone responds well to this combination, and given the nature of these substances, it seems likely that the dosages and the relative timing have a large influence on how the experience develops. I’ve heard three relatively “established” ways in which people use this combination. First, you have the school that says that you should take the MDMA at or slightly after the peak of the effects of LSD, that is 4-4:30h after taking it. The reasoning here is that you don’t want to be caught coming down from the MDMA while still having a long time to go on LSD since the acid could enhance the feelings of the comedown. The delayed gratification also pays-off by giving you several hours to face the problems you want to solve unaided and see how far you can get before the mood boost of MDMA gives you the determination to be contented with it.

The second school of thought about candy-flipping says that the biggest factor in how psychedelic experiences turn out is how they start. So what you want to do is take the MDMA 1 to 1:30 hours before the acid. This way, you only embark upon the inner journey when you are already in a really, really good chill state of mind. Some people report that the acid picks up the empathogenic quality of the state, amplifies it, and carries it on for much longer than if you had only taken MDMA alone.

There are many proponents and detractors to both of these schools. What I’ve seen more or less everyone agree on is to avoid taking substantial doses of LSD and MDMA (e.g. 200micrograms LSD + 120mg MDMA) at the same time. Apparently this is simply just too overwhelming and synergistic to be enjoyable, often causing a lot of nausea and palpitations.

The third school, however, is to take only a small dose of both at the same time. Say, 35micrograms LSD and 35mg MDMA. This apparently is an extremely positive combination. The experience is not mild due to the synergy, and it seems to provide an open, creative, level-headed mindset for many hours without much of a comedown or hangover. As with everything here, your mileage may vary.

Psychedelics + Dissociatives: Psychedelics and dissociatives have profound non-linear mixing effects. According to multiple sources, the right combination of LSD, Ketamine, and THC can give rise to a “free-wheeling hallucination“. This is a state of consciousness in which you gain a great degree of conscious control over the contents of the hallucinated world, so that you can project your will by saying “let there be a chair in front of me” and you will see it manifest in exquisite detail. You can rotate, translate, invert, fibrate, and project the chair in any way you want, as if you were now able to use your brain as a very general game engine of consciousness. That said, even when this doesn’t happen, the combination of psychedelics and dissociatives is ridiculously synergistic. People report getting stuck in extremely energetic time-loops akin to those caused by psychedelics and cannabis, but more powerful (cf. trip report of DMT + nitrous oxide). Steven Lehar calls the effect where the presence of a psychedelic changes the quality of a dissociative as “dissociative coloring”. I’ve been amazed at the fact that there is no mistaking when someone has previously experienced LSD and nitrous together. You don’t get reactions like “it didn’t do much for me”. This combo usually has a special place in the memory of a person who has experienced it. Eyes brighten, curiosity sparks. I’ve been asked on multiple occasions “what do you think is going on with the strange synergy between LSD and nitrous?” Now, 5-MeO-DMT and DMT are very different, and the LSD + nitrous state seems to have some resemblance with the 5-MeO-DMT state. They share that strange feeling of becoming a kind of saturated resonance box. The feeling is one of becoming a vessel full of coordinated and coherent vibrations that unearth and dissolve internal boundaries and blockages. The process inherently blocks your ability to conceptualize in a dualistic way. The cognitive content of the state is better captured by a huge blinking sign that reads “THIS, THIS, THIS” on repeat rather than the more usual “that thing over there connected to this over here, modulated by what happens there” kind of cognitive state we are more familiar with. DMT on its own is very different than this, in that the mental formations and patterns of binding that emerge are extremely specific, detailed, and irreducibly complex. Not so on the upper ranges of the dissociative and psychedelic cocktail, where the resonance is profound and the asymmetries needed to store complex information are constantly smoothed out by the ongoing full-body bath of reverb. (cf. Neural Annealing).

Dissociatives + Empathogens: According to several trip reports and credible personal communications, taking ketamine while on MDMA can bring back “the magic” that one only ever experienced with MDMA the first few times using it. Also MDMA and nitrous have profound research-worthy synergy.

Potentiation: Shulgin reported that substances that don’t feel psychedelically active on their own may nonetheless potentiate the effects of other psychedelics. For instance:

(with 160 mg of MDPR followed at 2h by 100μg LSD) This proved to be almost too intoxicating, and a problem arose that had to have a solution. The entire research group was here, and all were following this same regimen. Two hours into the second half of the experiment a telephone call came that reminded me of a promise I had made to perform in a social afternoon with the viola in a string quartet. Why did I answer the phone? My entire experience was, over the course of about 20 minutes, pushed down to a fragile threshold, and I drove about 10 minutes to attend a swank afternoon event and played an early Beethoven and a middle Mozart with an untouched glass of expensive Merlot in front of me. I could always blame the booze. I declined the magnificent food spread, split, and returned to my own party. Safely home, and given 20 more minutes, I was back into a rolling +++ and I now know that the mind has a remarkable ability to control the particular place the psyche is in. 

(Entry on MDPR, from PIHKAL)

More common than the above, ayahuasca is intrinsically a drug combo primarily of the potentiation kind. As mentioned before, cannabis not only alters but also potentiates the effects of psychedelics. It is worth mentioning there is a community of people who believe that noopept (a cholinergic nootropic, see below) can potentiate MDMA. While there is some evidence that MDMA is itself mildly cholinergic– and thus provides a sense of mental clarity in addition to the loved-up feeling- too much cholinergic action tends to make people feel rigid, robotic, and hyper-cerebral. I am therefore personally skeptical of the benefits of combining something like noopept with MDMA, as the potentiation of some of its qualities may come at the cost of reduced emotional sensitivity. Why trade a feeling of renewed innocence and receptivity with calculating prowess? I doubt this is the best use of a roll.

Anti-tolerance Drugs: This is a category of combinations with tremendous potential to relieve suffering, to the extent that I think of it as a humanitarian tragedy that there are no concerted research efforts currently in this direction. Sufferers of chronic pain and treatment-resistance depression could make use of drugs that help them keep the tolerance to the drugs they depend upon for having a livable life under control. I know this has a lot of the ring of turtles all the way down (“when are you going to get the anti-tolerance drugs for anti-tolerance drugs? And then the anti-tolerance for anti-tolerance for…”) but I am sincere when I say that looking here may pay off in spades. Already we see ibogaine doing other-worldly magnificent things to cure addiction and reverse tolerance. Who knows what a large targeted research program with this focus may discover. Some examples of anti-tolerance drugs include proglumide, ibogaine, and black seed oil for opioids, and flumazenil for benzodiazepines.

Prevent Physical Side Effects: Epidemiological data suggests that chronic or heavy use of 5HT2B agonists may lead to heart valve disease (cf. Fen-Phen), which does not bode well for the long-term (as opposed to acute) safety of many psychedelic compounds. Now, neuroscientist Thomas Ray believes that 5HT2B may be necessary for some of the characteristic psychedelic action of entheogens, so blocking it altogether may come at the cost of eliminating the reason why the drug is interesting. That said, we do know that 5-MeO-DMT is profoundly psychedelic and yet has negligible 5HT2B activity. It would be very useful to know what happens when one combines psychedelics with heavy 5HT2B affinity, like 2C-B and DOB, with 5HT2B antagonists (usually prescription medicines). Would blocking 5HT2B agonism avoid cardiotoxicity? And what would the drug feel like then? Another interesting lead is the affinity of compounds like 2C-E and 2C-T-2 to the 5HT3 receptor, which is predominantly in the gut and modulates feelings like nausea. Additionally, since 5HT3 antagonists are antiemetic it really stands to reason that taking one before e.g. tripping on shrooms may give you a much less, ahem, visceral experience. Finally, I would like to explore the implications of the fact that of all of the compounds in Ray’s study the only one with significant affinity for calcium channels is MDMA. Would this be related to its neurotoxicity? And would taking a calcium channel blocker prevent it? It might still be wise regardless simply as a way to lessen the cardiac load of the compound.

Nootropic Stacks (cf. the Qualia Pill):  Many people who explore nootropics make “stacks”. That is, rather than taking only piracetam, they might take a combination of piracetam, aniracetam, pramiracetam, coluracetam, and l-tyrosine. I suspect that this is popular because most nootropics are pretty mild and often hard to notice, and people want to be able to feel the effects. I generally do not think this is sensible, though, as we don’t understand these substances well enough. More so, branded “nootropic stacks” can have upwards of 30 different psychoactive substances crammed together in half a dozen pills you are supposed to take daily. While I do think there are likely gems to be found in the vast combinatorial space of cognition-boosting chemicals, I simply do not see any way in which the current major brands of nootropic stacks could have done the type of research needed to find them. I therefore do not personally recommend you go out and try such combos, at least not until we know a lot more about how to do combinations properly. If you want to try nootropic stacks, I’d recommend you start with small doses of two or three well-researched nootropics at most and do your own research thoroughly before settling on a particular combination.

NO-MISMATCH-PATTERN

LSD + DMT Visual Replication

Psychedelics and Psychedelics: A classic psychedelic combo that I’ve heard a lot about is LSD + DMT. The state that emerges from this combination is apparently unique, though if you take enough DMT the LSD fades into the background. Apparently psychedelics tend to have a characteristic spectral effect on your brain’s harmonics (see: Connectome-Specific Harmonic Waves on LSD), which manifests in the form of experiencing “vibes of different frequencies” specific to the drug you are taking. The case of LSD and DMT is very interesting, since their characteristic frequencies are sufficiently far apart (to put a number on it, LSD may be in the vicinity of 18Hz while DMT may be close to 30Hz) that they can be separated easily. You thus get a spectral effect of two peaks interfering with one another, oftentimes creating a powerful 3D grid of Moiré patterns, like a super-charged version of the “regular” DMT Chrysanthemum. As a method for spectral analysis, studying the beat patterns of psychedelic drug combos could go a long way in formulating a systematic characterization of their phenomenology. Speculatively, this may even allow us to come up with specific psychedelic drug cocktails that produce maximally consonant harmonious effects.

Idiosyncratic Responses

A final thought to add to this section concerns the fact that people respond differently to drugs. One can reason that if drug A affects 20% of people in a different way while drug B affects 10% of people in a different way, that A + B would lead to 4 different kinds of responses. More so, the more drugs you pile on top of each other, the more specific and individualized the response would be. I think that this is likely true in the general case, but I would argue that it is not universally true. A useful analogy here is with the way people respond to the scent of different molecules: you may lack the gene that encodes the receptor for a particular molecule, but perfumes usually have 30 or more scent-contributing molecules, so the experience of a perfume may be more similar between people than their experience of individual molecules. At the extreme, we have the phenomenon of “white noise scent” where once you mix 40+ molecules in equal (intensity-adjusted) proportions that span scent-space, it all starts smelling the same. The notion of “scent entropy” can be imported to drugs as well: I would expect a kind of inverted U-curve for “how idiosyncratic” the responses to drug combinations are as a function of the total entropy of the combo.

Drug Cocktails From First Principles

The way we aim to understand psychoactive substances at the Qualia Research Institute is in terms of the way they modify the neuroacoustic profile of the brain. And while this is what I see as the most promising approach moving forward, I believe that there is nonetheless a lot of low-hanging fruit at the receptor level of analysis.

The first time I’d thought of trying to emulate the effects of a drug using a cocktail of other drugs came up years ago when I found out that MDMA is likely neurotoxic. At the time I thought perhaps it was just a matter of getting the right dopaminergic, serotonergic, and oxytocinergic activity going for you to replicate the MDMA high. It’s a good thought, and some people have taken it to heart, such as the creators of “Poly”, an MDMA-like cocktail (cf. Kisspeptine). But as we’ll see, MDMA is more complex than that, and we may need to consider far more variables to make a “credible MDMA substitute”.

Looking beyond drug combos of only two or three drugs, and with a nod to concepts from the field of high-entropy alloys (HEAs), we could start thinking about the secret gems to be found in the vast combinatorial space of “high-entropy drug combos”. But what kind of principles could we use to safely combine 5+ drugs? The full story will probably be much, much more complicated than the following approach, but it is still nonetheless worth exploring as a first pass. Namely, to break down each drug in terms of their receptor affinity profile and then use those affinities additively to create arbitrary “synthetic” receptor affinity profiles. There are many reasons why this might not work: receptor affinity may not work linearly or have a clear rule-based behavior. For instance, it is still unclear if a single drug that has affinity for key serotonin receptors (say 5HT2A, 5HT2B, and 5HT7) in addition to working as an NMDR antagonist would produce the same feeling of “synergistic action” as there is between psychedelics and dissociatives. More so, there could be additional intra-cellular signaling specific to each molecule, so that two molecules that work as agonists with the exact same 5HT2B affinity may have different downstream effects inside the neuron, and then those intracellular effects might have phenomenological properties of their own. But leaving all of those caveats and unknowns aside for a moment, what would it look like to create drug cocktails with this method?

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True for both people and drugs!

After giving it some thought I realized that the problem can be reduced to a non-negative least squares (NNLS) optimization (non-negative because, as they say: “you can always take more drugs, but you cannot take less drugs”). It turns out there are already open source implementations of algorithms that solve this optimization problem (for both R and Python)*. So I downloaded the data from the famous Thomas Ray study of psychedelic receptor affinity and played with the data and the non-negative least squares method in a Jupyter notebook for a bit. The first thing I tried was to create a compound like 2C-B but better. Under dubious- but not entirely random- assumptions, I set the desired receptor affinity to be that of 2C-B but with the following modifications: to have the 5HT2B affinity be as low as possible in order to minimize cardiotoxicity concerns, and borrow from MDMA’s unique profile the hypothesis that the Imidazoline receptor is related to heart-opening effects. Additionally, I modified the receptor profile so that the drug would give you more focus than 2C-B by having a higher affinity for the dopamine receptors. To top it off, I racked up the desired receptor affinity for 5HT7, as it has been implicated in providing the more utterly mind-blowing power of psychedelics. I entered these modifications into the NNLS optimizer and the output I got was**:

0.48*2C-B + 0.337*5-MeO-DMT + 0.116*MDMA + 0.043*cis-2a + 0.016*6-F-DMT + 0.005*Mescaline

I see, so since 2C-B is still the backbone of the desired affinity pattern, it appears in high proportion in the mixture as a kind of “base” on top of which the modifications are made. It makes sense that 5-MeO-DMT would come next as it is pretty selective for 5HT7 (remember, the most literally mind-blowing chemical), and MDMA would follow due to the desire for Imidazoline affinity. That by the way, is also probably partly why the formula contains a pinch of Mescaline, to round up that Imidazoline for good measure. I then decided to relax the 5HT7 requirement and instead increase the 5HT6 and 5HT5A, and got the following formula:

0.038*Lisuride + 0.273*2C-B + 0.056*DMT +0.079*Mescaline + 0.15*MDMA + 0.377*RR-2b + 0.018*Ibogaine

And this now looks pretty different. After playing like this for a while, it occurred to me to use this technique to basically try to reconstruct a drug using a non-negative linear combination of the remaining drugs available. Imagine for example that you are stuck in quarantine at your house and you don’t have any 2C-B to kill time (I know! Very relatable isn’t it?), but you do somehow happen to have an assortment of hundreds of other unscheduled random research chemicals. Could you combine them in such a way that you approximate the effects of 2C-B? Well, let’s see.

Here are the “drug reconstructions” the method derives (again, please, don’t try this at home):

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I am pleasantly surprised to see the formulas actually do seem pretty intuitive to me. Take for example the DIPT reconstruction. The top two ingredients are 5-MeO-DIPT and DPT, which are the two closest structural analogues of DIPT in the dataset. Or take the one for DOB: this is the amphetamine version of 2C-B, so it makes sense that both an amphetamine psychedelic (Aleph-2) and 2C-B would make up the top two ingredients. Or consider 5-MeO-DMT, with its most prominent ingredient being 5-MeO-TMT, which is one carbon atom away in terms of structure. Or see how Mescaline’s heart-opening effects are well represented by its reconstruction with MDMA and MDA, while TMA contributes the receptor affinity characteristic of the trimethoxy class of functional groups, along with another Mescaline-like phenethylamine, 4C-T-2. Alas, here is where an imperfect understanding of drug interactions could come and bite us in the ass: if 4C-T-2 is anything like 2C-T-2, it might have some MAOI action, which could be potentially very dangerous to combine with compounds like MDMA. Needless to say, before you go out and try these crazy drug cocktails, we first need a thorough understanding of each drug well beyond just its affinity to “only” 30 or so receptors.

Now, not every reconstruction makes sense to me, and really only a few substances have what I would call a descent mean squared error. See the receptor affinity tables below for examples of both successful and unsuccessful reconstructions (only non-zero entries shown):

DOB and 2C-T-2 have some of the lowest errors in the sample, meaning that their reconstructions are pretty good, while Ibogaine and MDMA have two of the worst error rates, and their reconstructions are still obviously pretty far from the goal. Naturally, if we were ever to test this method in the lab (with e.g. a drug discrimination paradigm) we would probably start with the most accurate reconstructions first. For instance, train rats to distinguish between 2C-B and DOB, and see if administering the (2C-B-containing) “DOB reconstruction” makes the rats think they got DOB rather than 2C-B.

Master Druggist (Synapse? Dendrite?)

I would like to conclude this essay with an interesting speculation: what if we developed drug combos like we develop perfumes? It is my appreciation that it takes a very high level of intelligence, domain expertise, and psychological robustness to be able to contribute usefully to the field of psychonautics. Sasha Shulgin spent over 30 years taking hundreds of completely new drugs, and I would very much trust his judgement about what makes a great psychedelic drug combo than I would trust a random BlueLight or Erowid user. (As an aside: Shulgin was extremely cautious in his approach, but he certainly wasn’t doing some of the low-hanging fruit on safety, such as wearing a heart monitor or measuring his blood pressure when taking a new drug, for starters. Future systematic psychonautic work should also record as much biometric data as is feasible). You wouldn’t put on a perfume made by someone who has only ever worn Axe, would you? Training a “Nose” takes up to 7 years, and it involves becoming deeply familiar with the scent of a long list of molecules, accords, and perfumes. Likewise, I’d expect that in order to be qualified to find extremely good drug combinations, one would first need to become familiar with the effect of many different individual drugs, “natural drug accords” (e.g. peyote), and designed drug cocktails. Only once you have an intuitive sense of how e.g. the sigma receptor interacts with the 5HT1A receptor would I trust your judgement about adding a pinch of agmatine to your already convoluted mixture of 20 psychoactive substances. A Super-Shulgin Academy could train people to be professional drug cocktail makers (if perfumers are called “Noses” would we call Super-Shulgin certified cocktail makers “Dendrites”?). As discussed above, this assumes that we can do this safely, which I suspect will be possible once we map out the space of dangerous combinations and receptors we shouldn’t mess with to avoid side effects like cardiotoxicity (e.g. 5HT2B, 5HT3A, calcium channels, etc.).

You come to the master cocktail designer with a general concept for a new recreational drug, and they would come up with activity profiles that best evoke those feelings. The Dendrite would select from hundreds or thousands*** of pure chemicals and accords to create your unique cocktail. As is the case with Noses in the perfume industry, a Dendrite would tend to have a set of about one to two hundred “frequently used” compounds, and a dozen or so “signature” ones they’re deeply familiar with and that usually reveal who the Druggist is, if found in large proportions in the end product. Of course there would be “house favorites” (e.g. the classic “ambroxan bomb” of Dior fragrances for men) and chemical fads (e.g. the wide adoption of Iso E Super in 90s perfumes). Every year would come with a new season of amazing, safe, and uniquely interesting recreational drug cocktails.

In perfumery you find both natural and synthetic “accords”: “Violet reconstructions” attempt to emulate the smell of violet but in a much more long-lasting, storable, and versatile way. Good Dendrites would not only use “natural accords” such as “peyote” or “marijuana plant” but would also make their own, aided with computer models and datasets of trip reports along with their own first person experiences. In both perfumery and professional drug cocktail making we would study accords packed with combos of qualia-triggering chemicals, and a Dendrite could be known not only for making good final products, but for making excellent accords with predictable and desirable effects.

To finalize the analogy (and this article) we could also discuss the way in which perfumes feel “broad spectrum” thanks to being constructed by combining “top, heart, and base notes”. Roughly speaking, top notes tend to “feel higher frequency” (such as citric scents) while base notes tend to “feel low frequency” (such as woody scents), not unlike how a symphony will tend to combine sounds across the spectrum. The most interesting, voluptuous, and commercially viable combos would also probably have a broad spectrum of activity. They would be anxiolytic, exciting, relaxing, trippy, and empathogenic to various degrees all at once. They would combine fast, slow, and spiritual euphoria in a single power punch of qualia cornucopia. As such, each drug cocktail made this way would entail an entire worldview – a whole realm currently hidden in the vast state-space of consciousness.



* For an intuition: recall from linear algebra that a basis of n linearly independent vectors span an n-dimensional vector space. When the vector that you are trying to reconstruct is not in the span of your basis, the best you can do is to project your vector to the nearest hyperplane of the spanning space. Adding the constraint that you can only make non-negative linear combinations with your basis vectors, you find that the span will look like an ‘inverted pyramid’, and the least-squares solution will be the point of that inverted pyramid that is closest to your desired vector. This is why most of the reconstructions only use a subset of the available drugs in the dataset. In most cases, the desired vector (i.e. affinity profile in this case) will be outside of the inverted pyramid of the non-negative span, and the closest hyperplane will be a linear combination of only a subset of the building blocks- those which span that particular hyperplane. I.e. the solution is the projection to the nearest hyperplane segment covering the non-negative span. This is what the NNLS method is doing under the hood.

** Note: It’s important to point out that these are not dosages. The coefficients provided by the non-negative least squares method apply to the normalized affinity “npKi“, which is the receptor affinity normalized by the highest affinity among the receptors. The coefficients will be correlated with “proportion of a standard active dose” but there will be an error caused by the pretty tricky confounder that molecules vary in their “breadth of affinity”. Additionally: the psychoactivity of each receptor is not the same, we are not considering saturation effects, the difference between partial and full agonists is not taken into account, downstream effects are ignored, etc. etc. Needless to say, there is still quite some work to be done to transform these coefficients into meaningful dosages.

*** List of Psychoactive Drugs a professional Dendrite would be expected to be familiar with:

L-Tyrosine, L-DOPA, Apomorphine, Flumazenil, CPZ, BPAP, PPAP, Cabergoline, DAR-0100, Lisuride, Pergolide, Pramipexole, Rotigotine, Biopterin, PLP, Aminepetine, PCP, Marijuana, Dextromethorphan, Isoflavones, Citicoline, Metadoxine, Arecoline, Niacinamide, Paraxanthine, a-GPC, Acetylcarnitine, AR-R17779, GTS-21, Ispronidine, PHA-543,613, SSR-180,711, WAY-317,538, Hopantenic Acid, IDRA-21, Propentofylline, PRL-8-53, Trytophan, Picamilon, Betahistine, A-349,821, Cipoxifan, Creatine, Mildronate, Pregnenolone, Nisoxetine, Orexin, CP-39,332, Esreboxetine, Daledalin, AM-1248, Phenoxybenzamine, Symbescaline, Phentolamine, Isomescaline, Tolazoline, a-Methylfentanyl, Ketamine, Dichlorpane, 3-meo-pcp, Hex-en, Paraflourofentanyl, 3-Methylfentanyl, Metofoline, Buscaline, O-DT, Nortilidine, Thiobuscaline, Dizocilpine, Rolicyclidine, Phenescaline, Tenocyclidine, Methoxyketamine, pFPP, 5-me-MDA, 4-MAR, 1,4-Butanediol, 2-Methyl-2-Butynol, GHV, GVL, Mebroqualone, Benzylbutylbarbituates, Phenmetrazine, 3-Fluorophenmetrazine, Crack, Cocaine, Coca, Kava, Phenylacetylindoles, Benzoylindoles, Napthoylindoles, Adamantoyindoles, Pineapple Sage, Kokum, Brahmi, Artic Weed, Skullcap, Salvia Splendens, Coriander, Rhodiola Rosea, Velvet Bean, Bitter Orange, St. John’s Worth, Grape Seed Extract, Tulsi, Blessed Thistle, 3-Desoxy-MDA, Skatole, Isoindole, Indole, Benztropine, Diphenhydramine, Niaprazin, Doxylamine, Alaproclate, Zopiclone, Ifoxetine, Methylmethaqualone, Panuramine, Meta-Tyramine, Para-Tyramine, 2M2B, Pirandamine, SB-649,915, Epinephrine, Mepyramine, Octopamin, Delucemine, Oxidopamine, β-Methylphenethylamine, Mesembrine, Psuedoephedrine, Etolorex, Cathine, Cathinone, Ethcathinone, Norfenfluramine, Fenfluramine, Phentermine, Metaescaline, n-Ethylbuphedrone, Naphyrone, Pyrovalerone, Isopropylamphertamine, Clobenzorex, Pholedrine, Chlorphentermine, Xylopropamine, DON, DOPR, TMA, Methyl-BOB, Tetramethoxyamphetamine, 4-MTA, Bromatane, Hydroxyzine, BNC-210, CL-218,872, L-838,417, SL-651,498, S32212, 6-CAT, TAP, ETAI, IMP, Lorxaserin, Cisapride, Tegaserod, AS-19, E-55888, LP-12, LP-44, LP-211, Etoperidone, Lorpiprazole, Lubazodone, Mepiperazole, 5-TASB, TB, 3-TE, 4-TE, 2-TIM, 3-TIM, 4-TIM, 3-TM, 4-TM, TMA, TMA-2, TMA-3, TMA-4, TMA-5, TMA-6, 3-TME, 4-TME, 5-TME, 2T-MMDA-3a, 4T-MMDA-2, TMPEA, 2-TOET, 5-TOET, 2-TOM, 5-TOM, TOMSO, TP, TRIS, 3-TSB, 4-TSB, 3-T-TRIS, 4-T-TRIS, 44-BMAR, 3-MOMC, Prolintane, SDB-001, AB-FUBINACA, Dichloromethylphenidate, AB-PINACA, MN-24, 5F-MN25, A-836,339, ADBICA, 5F-NNEI, RCS-4, RCS-8, MPHP, 6-APDB, 4-HMP, EDMA, a-PBP, Methylhexamine, a-PPP, 4-FMD, EIDA, Phenylphrine, UWA-101, MPBP, RH-34, F-2, F-22, MR-2096, Adrenochrome, AET, Carbogen, DOB, DOM, Desmorphine, Ethylcathinone, Ehylene, GHV, Hypocretin, mCPP, MDPR, Methaqualone, TFMPP, CPP, MeoPP, A2, Salvinorin A, Scoplamine, TMA-2, BDO, 2c-B-FLY, 4-Flouromethcathinone, 4-HO-MPT, U4EA, 4-MTA, Phenylpiracetam, Aniracetam, Coluracetam, Pramiracetam, Melatonin, NRG-3, Theobromine, A834-735, Oxytocin, NZT-48, Heroine, 3-HO-PCP, MAOIs, 4-MeO-PCP, 3c-P, 5-IAI, Atropine, 5-IT, Bufotenin, 5-MAPB, 4-Aco-MiPT, 6-MAPB, ALD-52, AMMI, MET, D2PM, DET, CBD, CBN, LY-2183240, SF-SDB-005, AM-404, EG-018, DXM, FDU-PB22, AL-LAD, 3-MeOMC, 2-MeO-Diphenidine, 4-MPD, bk-MDMA, 4-MeO-a-PVP, GHB, 4-MeO-PBP, MBDB, 4-MeO-PV9, Fentanyl, 4F-PV8, a-PBT, BDB, a-PVT, 2-FMA, Dibutylone, 5-Meo-DiPT, Diclofensine, Methcathinone, DL-4662, MDEA, MDPPP, Methylone, Butylone, NEB, Phenibut, PV-8, GABA, 25B-NBF, Etaqualone, 5-API, Ethylone, Pentadrone, 4F-PVP, 25C-NBF, BZ-6378, C30-NBOMe, RH-34, MDAT, MDMA, MDMAI, Dimethocaine, Synthacaine, 3β-FBT, 5-MeO-BFE, 3,4-DMMC, AM-1248, MTTA, AM-2233, URB-597, AM-694, AM-087, BAY-38-7271, AB-005, A-796260, URB-754, 2-DPMP, a-PVP, 25N-NBOMe, 5-MeO-NiPT, Dexmethylphenidate, Buphedrone, RTI-111, Pentylone, 25I-NBF, Flourotropacocaine, Flourococaine, Cocaethylene, 25D-NBOMe, 25E-NBOMe, DMT, 5-Meo-DMT, 2C-I, 2C-E, 25I-NBOMe, 25I-NBOH, 25C-NBOMe, MXE, MDA, MDE, Mescaline, Ibogaine, Bromo-DragonFLY, Salvinorum, RU-28306, 2NE1, Psilocybin, HOT-7, JWH-018, JWH-250, 5-Meo-EiPT, AM-2201, 5-APDI, BZP, BZ, 4-MEC, MDPV, Bakers Ammonia, THC, THCv, Chloral, Chlorabutynol, MT-45, 5-Methyl-Ethylone, Methylphenidate, Ethylphenidate, 6-APB, 5-APB, Muscimol, 5-MeO-MALT, AKB48, 3,4-CTMP, PB-22, Diphenidine, UR-144, Flubromazepam, HU-210, MPA, XLR-11, MN-18, Naltrexone, STS-135, Gabapentin, 5-MAPB, Nitrous, Etizolam, Mephedrone, Pyrazolam, Methedrone, AH-7921, Phenazepam, AMT, OxyNEO, DPT, 5-MeO-AET, 4-Aco-DMT, EAM-2201, 5-MeO-DALT, 5-MeO-AMT, Acefentanyl, Ehylphenidate, 4-HO-MiPT, THJ-2201, 5-APDB, 5-EAPB, 4-HO-DPT, DOC, bk-2c-B, Escaline, THJ-018, 4-HO-MET, 2-AI, 2-MeO-Ketamine, Methoxphenidine, Ketamine, 2c-EF, Methamphetamine, Dextroamphetamine, Nitracaine, DALT, IAP, 4-fa, 2-Me-DMT, 4-fcocaine, Isopropyl Nitrate, 5-MeO-TMT, Piracetam, Amatadine, Choline, Memantine, 5-HTP, Camfetamine, Methallyescaline, LSZ, LSA, NBOMe-Mescaline, Loperamide, LSB, 25P-NBOMe, 25G-NBOMe, 3-MeO-PCE, MAM-2201, PCP, MPTP, MDAI, DOI, BB-22, EA-3167, BDF, L-Theanine, Dimethylone, Hydrocodone, Codeine, Morphine, Dilaudid, Oxycontin, Alpralozam, Diazepam, Fentanyl, Soma, Suboxone, Marinol, Seroquell, Trazodone, Lithium Bicarbonate, Abilify, Methadone, Amitriptyline, Strattera, Chloral Hydrate, Bromazepam, Buperonorphrine, Bupropion, Chlordiazepoxide, Clonidine,Clonazepam, Cyclobenzaprine, Dramamine, Benadryl, Ethchlorvynol, Fluoxetine, Tianeptine, Amineptine, Flurazepam, Metaxalone, Mirtazapine, Nalaxone, Nimetazepam, Oxymorphone, Paroxetine, Zopidone, Pregabalin, Promethazine, Risperadone, Selegiline, Sertraline, Sumatripan, Tiagabine, Propofol, Propanolol, Tiletamine, Zolpidem, Lotus, Aloe, Datura, Calendula, Chacruna, Galangal, Chaliponga, Chamomile, Damiana, Fever Few, Nightshade, Ginseng, Foxglove, Lavender, Henbane, Mugwort, Hemlock, Monkshood, Dream Herb, Capsaicin, Amanita, Hawaiian Baby Woodrose, Ergot, Hops, Imphepho, Indian Warrior, Kanna, Dagga, Kratom, Mandrake, Valerian, Nicotiana Tobacum, Nicotiana Rustica, Mimosa Hostilis, Morning Glory, Nutmeg, Opium Lettuce, Poppy, Sinicuichi, Syrian Rue, Tree Tobacco, Wormwood, Yohimbe, Yopo, Khat, Peyote, Cannabis, Catnip, Phalaris, San Pedro, Soma (ancient), Chacruna, Acacia, Ephedra, Mulungu, Mullet Fish, Siganus Spinus, Fugu, Sting-ray Venom, Bufo Alvarius, Epipedobates Tricolor, Waxy Monkey Frog, Salamandra Salamandra, Cobra & Scorpion Venom, Reindeer Urine, Glomeris Marginata, Sergeant Major, Grouper, Bluefish, Brass Beam, Flathead Mullet, Golden Goatfish, Rabbit Fish, Goat Fish, Adrafinil, DHEA, Dilantin, DMAE, Fipexide, Gerovital, Ginko, Black seed oil, HGH, Hydeigine, Meclofenoxate, Modafinil, Oxiracetam, Phenyton, Vasopressin, Vinopocetine, Bee Venom, Monkey Frog, UCM-707, AM-1172, VDM-11, VDM-13, OMDM1, OMDM2, LY-2318912, O-2093, OL-135, URB-597, URB-532, AEM, AL, ALEPH, ALEPH-2, ALEPH-4, ALEPH-6, ALEPH-7, ARIANDE, ASB, B, BEATRICE, BIS-TOM, BOB, BOH, BOHD, BOM, 4-Br-3,5-DMA, 3-Br-4,5-MDA, 2C-B, 3C-BZ, 2C-C, 2C-D, 3C-E, 2C-F, 2C-G, 2C-G-3, 2C-G-4, 2C-G-5, 2C-G-N, 2C-H, 2C-N, 2C-O-4, 2C-P, CPM, 2C-SE, 2C-T, 2C-T-4, 2C-T-2, 2C-T-7, Ψ-2C-T-4, 2C-T-8, 2C-T-9, 2C-T-13, 2C-T-15, 2C-T-17, 2C-T-21, 4-D, β-D, DESOXY, 2,4-DMA, 2,5-DMA, 3,4-DMA, DMCPA, DMMDA, DMMDA-2, DMPEA, DOAM, DOBU, DOEF, DOET, Ψ-DOM, DON, DOPR, E, EEE, EEM, EME, EMM, ETHYL-J, ETHYL-K, FLEA, G-3, G-4, G-5, GANESHA, G-N, HOT-2, HOT-17, IDNNA, IM, IP, IRIS, J, LOPHOPHINE, M, 4-MA, MADAM-6, MAL, MDAL, MDBU, MDBZ, MDCPM, MDDM, MDHOET, MDIP, MDMC, MDMEO, MDMEOET, MDMP, MDOH, MDPEA, MDPH, MDPL, MDPR, ME, MEDA, MEE, MEM, MEPEA, META-DOB, META-DOT, METHYL-DMA, METHYL-DOB, METHYL-J, METHYL-K, METHYL-MA, METHYL-MMDA-2, MMDA, MMDA-2, MMDA-3a, MMDA-3b, MP, MME, MPM, ORTHO-DOT, P, PE, PEA, PROPYNYL, SB, TA, 3-TASB, 4-TASB, Tropane, Vomeronasal Organ, Tropine, Hyosyamin, Dihydrokavain, Hyoscine, Myrcene, Ecgonine, 7-OH-DPAT, Benzoylecgonine, Sunifiram, Hydroxytropacocaine, Estrogen, Methylegonine Cinnamate, Estradiol, Catuabines, Estratetraenol, Phenyltropane, Androstenone, Civetone, Adrostenol, 5F-PB-22, Androstadienone, CBG, THCa, CBC, CBDa, Anandamide, 2-AG, CBL, CBDv, CBCv, CBGv, CBGm, Ibogaine, Noribogaine, Tabernanthine, Coronaridine, Ibogamine, Vaocangine, 18-MC, 5-MeO-Alkyltryptamine, β-Carboline, Tryptoline, Pinoline, Harmane, Harmaline, Harmine, Harmalol, Harmalan, Harmanamide, Acetylnorhormine, Bufotenin Oxide, DMT-N-Oxide, 5-MeO-Tryptamine, 5-OH-DMT, 5-MeO-DMT-Oxide, 3,4-Dimethoxyphenylamine, 6-MeO-Harman, Anethole, Safrole, Estragole, Monolignol, Pukateine, Glaucine, THP, Nantenine, Thujone, Lagochilin, Nicotine, Carbachol, Methacholine, ME-18-MC, 18-MAC, Tryptamine, β-Methyl-Phenethylamine, NMT, Voacanga Africana, Vachellia Farnesiana, Duboisia Hopwood, Acacia Victoriae, Anadenanthera Penegrina, Phalaris Aquatica, Echinopsis Lageniformus, Cylindropuntia Echinocarpa, Leptactina Densiflora, Fennel, Justica Pectoralis, Lactucarium, Glacium Flavum, Zornia Latifolia, Argemone Mexicana, Silene Undulata, Catharanthus Roseus, Desfontainia, Heimia Salicifolia, Lophophora, Sea Urchin Eggs, Bethanechol, Muscarine, Pilocarpine, Oxotremorine, Aporphine, Leonurine, Bungacotoxin, Tetrodotoxin, Taurine, Opiod Peptide, Streamlined Spinefoot, Blue-Spotted Spinefoot, Dusky Spinefoot, Marbled Spinefoot, Little Spinefoot, Salema, Phyllomedusa, Blue Sea Chub, Brow Chub, Conuict Surgeonfish, Yellowstipe Goatfish, Finstripe Goatfish, Acute Jawed Mullet, Coral Grouper, Platypus Venom, Slow Ioris Venom, Pygmy Slow Ioris Venom, Giant Leaf Frog, Gluten Exorphin, Soymorphin-5, Dermophin, 7-PET, Dimethyliambutene, Proopiomelanocortin, β-Endorphine, Dynorphin, Adrenorphin, Salvinorin B Methoxymethyl ether, Amindophin, Enkephalins, Salvinorin B ethoxymethyl ether, Opiorphin, Herkinorin, RB-101, DPI-221, Spinorphin, Kelatorphan, Delta-Pheylalanine, Thiorphan, Tynorphin, Hemorphon-4, Valorphin, Casomorphin, Gliadorphin, Rubiscolin, Deltorphin, MG6, MT-45, Myrophine, Acetorphine, Acetylmorphone, Actiq, Benzethidine, BU-48, BRL-52537, Pethidine, Naloxol, Betacetylmethadol, Methorphan, Bezitramide, RAM-378, Bromadol, Eriadoline, BW373U86, Thebaine, C-8813, Menthol, 8-CAC, Capperidine, Matrine, Chloromorphide, a-Chlorocodide, HZ-2, Codeinone, LPK-26, Codoxime, AD-1211, Conorfone, DADLE, Butorphanol, DAMGO, Semorphone, Dextromoramide, Sutentanil, Diampromide, Zenazocine, Difenoxin, Thebacon, Dihydroetorphine, Tilidene, Dimenoxadol, Xorphanol, Dipipanone, Dipropanoylmorphine, Doxpicomine, DPI-3290, Drotebanol, Endomorphin, Eseroline, Ethoheptacine, 14-Ethoxymetopon, Ethylmorphine, Etorphine, Etoxerdine, Furethidine, Heterocodeine, RAM-320, IBNtxA, IC-26, 1-Iodomorphine, Isomethadone, Ketobemidone, Ketorfanol, Lefetamine, Levorphanol, Loperamide, Meprodine, Metofoline, Metopon, Morpheridine, Morphine-N-Oxide, Morphinone, MR-2096, Nicocodeine, Nicomorphine, Normethadone, Ocefentanyl, Ohmefentanyl, Oxpheneridine, Oxymorphazone, Oxymorphol, Oxymorphone, Pentamorphone, PEPAP, Pericine, Phenadoxone, Phenempromide, Phenazocine, Pheneridrine, Phenomorphan, Picenadol, Piminodine, Piritramide, Proclilidine, Prodine, Proheptazine, Properidine, Prosidol, R-30490, R-4066, Ro4-1539, RWJ-394674, Sameridine, SC-17599, Methyldesorphine, Hydroxypethidine, 4-Fluouropethidine, Cannabis Indica, Cannabis Sativa, Cubensis, Hash, BHO, Delta-9-THC, 25TFM-NBOMe, 2C-B-BZP, 2CBFLY-NBOMe, 2CD-5Et0, 5-I-R91150, A-372,159, 2-Bromo-LSD, a-5IA, PWZ-029, L-655,708, TB-21007, 5-Ethoxy-DMT, 5-Ethyl-DMT, 7,N,N-TMT, VER-3323, YM-348, Alnespirone, 8-OH-DPAT, Aminorex, Batoprazine, 5-BT, BIMU-8, BMY-14802, BRL-54443, BW-723C86, 5-CT, CGS-12066A, Cinitapride, CJ-033,466, CP-135,807, CP-809,101, CP-93,129, CP-94,253, N,a,-DEPEA, Dimemebfe, RA-7, E-6801, E-6837, Eltoprazine, Methylsulfonylmethane, EMD-386,088, EMDT, ST-1936, Fluprazine, Indorenate, Jimscaline, L-694,247, Lasmiditan, APD-356, MMDPEA, LY-293,284, LY-310,762, LSD-pip, LPD-824, LSM-775, 5-MT, MBZP, Methyl-MMDA-2, a-MS, MK-212, Mosapride, Org 12,962, Org 37,684, Quipazine, 6-Nitroquipazine, NBUMP, 1-NP, 5-(Nonyloxy)Tryptamine, PHA-57378, PNU-181731, PNU-22394, Propylhexedrine, Prucalopride, PRX-03140, Psilocin, RDS-127, RH-34, Ro60-0175, Ro60-0213, RS-56812, RS-67,333, RU-24,969, RU-28306, SKF-97,541, SR-57227, Tandospirone, Tegaserod, TFMFly, pTMFPP, U-92,016A, SCA-136, TD-5108, Vortionetine, WAY-161503, WAY-208,466, WAY-629, Xaliproden, YM-31636, Zacopride, A-423,579, A-84,543, Abercarnil, 5-Br-DMT, Sugar, Acetildenafil AMMI 4C-D, AS-8112, Astemizole, Asymbescaline, Azapride, BAY-38-7271, BAY-59-3074, BAY-60-6583, Benproperine, Benzylmorphine, Berberine, 2-Pyrrolidone, JBIR-03(1), 1′-O-Acetylpaxilline, Penijanthine A, Emindole DA (1), Petromindole, Emindole SA (2), JWH-133, Napthylmethylindoles, Napthyolpyrroles, Napthylideneindenes, Cyclohexylphenols, Indole-2-Carboxamides, C3 Amino-Indoles, Cymserine, Hodgkinsine, Physostigmine, Psychotridine, Psychotria Colrata, Yuremamine, Gevotroline, Latrepirdine, BMY-7,378, Boldine, BP-897, Brexpiprazole, 4-Bromo-3,5-Dimethoxyamphetamine, Bromopride, Caroverine, CGS-20625, Cinchocaine, DAA-1097, DAA-1106, DOTFM, DMPEA, DMCM, Dyclonine, Ethylvanilin, Evoxine, Furoquinoline Alkaloids, Gabazine, GBLD-345, Rapacuronium, Mivacurium Chloride, Cisatracurium Besilate, DTC, Cloroqualone, Diproqualone, Mecloqualone, Methylmethaqualone, Eszopiclone, TP-003, TP-13, TPA-023, Y-23684, Pagoclone, Pazinaclone, Suproclone, Suriclone, Zapiclone, CGS-9896, NS-2664, NS-2710, Pipequaline, RWJ-51204, SB-205,384, ELB-139, Acamprosate, GABOB, N4-Chloroacetylcytosine Arabinoside, (+)-CAMP, CACA, AZD-3355, 1,4-Butanediol, XP19986, Rosarin, Rosavarin, Atagabalin, Gabapentin Enacarbit, Hopantenic Acid, Imagabalin, 4-Methylpregabalin, PD-217,014, Afloqualone, Rocuronium Bromide, Vecuronium Bromide, Pipecuronium Bromide, Pancuronium Bromide, Amyl Nitrate, Atracurium Besilate, BWA444, Benzylisoqualone, Papaverine, Protopine, HS-342, HS-347, HS-310, Emylcamate, Eperisone, Febarbamate, Flavoxate, Inaperisone, Acamprosate, Progabide, Tiagabine, Lanperisone, Mephenesin, HS-692, HS-693, HS-704, HS-705, HS-626, Chlorzoxazone, Cisatracurium Besilate, Curare, Cyclobenzapine, Dantrolene, Decamethonium, Difebarbamate, Dihydrochanclonium, Doxacurium Chloride, Gallamine Triethiodide, Gantacurium Chloride, Hexafluronium Bromide, Meprobamate, Metaxalone, Methocarbamol, Norgesic, Orphenadrine, Pancuronium Bromide, Phenprobamate, Pipecuronium Bromide, Premazepam, Promoxolane, Quazepam, Rocuronium Bromide, Silperisone, Sulazepam, Suxamethonium Chloride, Suxethonium Chloride, Tetrabamate, Tizanidine, Tolperisone, Gigantine, BAY-73-6691, Indiplon, Nitrosoprodenafill, Zaleplon, Udenafil, Sulfoaildenafill, Sildenafil, Ocinaplon, Alpidem, Bamaluzole, DS-1, Fadrozole, Fazadinium Bromide, Imidazopyridine, Minodronic Acid, Bisphosphonate, Miroprofen, Necopidem, AL-LAD, DBT, a.O-DMS, 2,a-DMT, a,N-DMT, ETH-LAD, a-ET, 4-HO-DBT, 4-HO-pyr-T, MBT, 4,5-MDO-DIPT, 5,6-MDO-DIPT, 4,5-MDO-DMT, 5,6-MDO-DMT, 5,6-MDO-MIPT, 5,6-MeO-MIPT, 5-MeO-pyr-T, 5-MeO-NMT, 6-MeO-THH, 5-MeS-DMT, PRO-LAD, pyr-T, a,N,O-TMS, Olprinone, Telcagepant, Febrifugine, Halofuginone, MK-0249, LY-156,735, Ramelteon, Tasimelteon, SL-164, Quinazoline, Albaconazole, Altaserin, ATC-0175, Canertinib, Cediranib, Doxazosin, Fluproquazone, Gefitinib, Katanserin, Lapatinib, Agmatine, Amantadine, AP-7, AP5, Aptiganel, CGP-37849, 7-CTKA, DCKA, DXO, MK-801, SL-82.0715, Esketamine, Ethanol, NEFA, Besonprodil, Gacyclidine, Gavestinel, Huperzine A, Ifenprodil, Indantadol, Metaphit, Memantine, LY-235,959, Lubeluzole, Levomethadone, Kynuretic Acid, Midafotel, Neramexane, Nitromemantine, PEAQX, Perzinfotel, 8A-PHDQ, Remacemide, Rhynchophylline, Sabeluzole, Tiletamine, Tramadol, Xenon, Hydroxchloroquine, Antrafenine, Bedaquiline, GSK-299423, JTC-801, JTE-907, LGD-2226, PBT-2, PF-2545920, SB-215,505, SB-277,011-A, SB-742,457, BHF-177, BHFF, BSPP, Cartazolate, CGP-7930, Clomethiazole, Etazolate, Etomidate, Felbamate, Fospropofol, Gaboxadol, Glutethimide, GS-39783, Ibotenic Acid, ICI-190,622, Isoguracine, Isonipecotic Acid, Loreclezole, Methyprylone, Allopregnanolone, 5a-Dihydroprogesterone, Progesterone, THDOC, Alfadolone, Alfaxalone, Ganaxolone, Hydroxydione, Minaxolone, Org-20599, Pregnane, Piperadone, Propanidid, Propofol, Pyrithyldione, ROD-188, Stiripentol, Thiomuscimol, Thymol, Tybamate, QNB (BZ), Scopolamine, Midazolam, Sodium Pentathol, Amobarbital, Blue 88, Adinazolam, Alphenal, Bentazepam, Bromisoval, Camazepam, Carbromal, Centalun, Chloralodol, Chronobiotic, Cinolazepam, Clorazepate, Cloxazolam, Cyclopyrrolones, Delorazepam, Dichloralphenazone, DPH, Doxefazepam, Doxylamine, Embutramide, Eplivaserin, Ethinamate, Ethyl Ioflazepate, Fludiazipam, Heptabarb, Oleamide, Org 21465, Org 25435, Paraldehyde, Phenobarbital, Propiomazine, Promethazine, Propylbarbital, QH-II-66, Glycine, Quetiapine, SH-053-R-CH3-2’F, Sulfonmethane, Tetrabarbital, Tetronal, Trional, Trytophol, Acaprazine, Acebrochal, Acetylglycinamide Chloral, Almorexant, Detomidine, Bromouriede, Benzoctamine, Barakol, Bekhterev’s Mixture, Fasiplon, Fenadiazole, Fluperlapine, JM-1232, Inebriating Mint, Ro41-3696, Methapyrilene, Minitran, Nisobamate, Oxanamide, Oxomemazine, Panadiplon, Pazinaclone, Pentabamate, Petrichloral, Potassium Bromide, Procymate, Saripidem, Vinybital, Vinbarbital, Valofane, Validolum, Valeric Acid, Unisom, U-90042, U-89843A, Triclofos, 2,2,2-Trichloroethanol, TCS-OX2-29, SX-3228, Suvorexant, Sigmodal, SB-649,868, 6-APA, 77-LH-28-1, Adimolol, Alfentanil, Amedanil, Amedalin, BMS-564,929, Binospirone, Carburazepam, Clazolam, Clobazam, Clobenzepam, Clotiazepam, Thienodiazepine, Brotizolam, CP-14145, Cyclazodone, CSP-2503, Cycloserine, Cytisine, Demoxepam, Chlordizepoxide, Dibenzepin, Dihydroergocorine, Dihydroergocristine, DHEC, Dihydroergotamine, 17-DMAG, Dimiracetam, Doliracetam, Droperidol, Dihydrotestosterone, Dutasteride, Edaravone, EGIS-12,233, Elfazepam, Elzasonan, Enilospirone, Ergoloid, Ergotamine, Ergocrytine, Ergocristine, Ergovaline, Etazepine, Evodiamine, Fenmetramide, Fenozolone, Flunitrazepam, Flutazolam, Flutemazepam, Flutoprazepam, Fosazepam, GW-803,430, Halazepam, Haloxazolam, Herbimycin, Horsfiline, HT-0712, Icilin, Clazepam, Indoprofen, Ipsapirone, Isatin, Ketazolam, KF-26777, Lofendazepam, Lopirazepam, Loprazolam, Lorazepam, Lormetazepam, Menitrazepam, Meclonazepam, Menitrazepam, NMSP, Mexazolam, THCI, THCII, THCIII, THCIV, THCV, Mosapramine, Motrazepam, NBQX, Nevirapine, Nimetazepam, Nitrazepam, Nitrazepate, Nitroxazepine, Nordazepam, Nortetrazepam, Oxazepam, Oxatomide, Paliperidone, Prazepam, Pivoxazepam, Pirquinozol, Pirenzepine, Pinazepam, Pemoline, Paraxazone, Palonosterone, Proflazepam, Propizepine, Razobazam, Revospirone, Ripazepam, Ro15-4513, Ro48-6791, Ro48-8684, Ro5-2904, Ro5-4864, Ro64-6198, Ropinirole, RPL-554, RS-102,221, SL65.0155, Spiroxatrine, Temazepam, Tetrazepam, Thozalinone, Tolufazepam, Triflubazam, Vardenafil, Ziprasidone, Zolazepam, Zomebazam, Zometapine, Pyrazolodiazipines, Triazolodiazipines, Estazolam, Flubromazolam, Triazolam, Nitrobenzodiazepines, Pentazocine, 8-HO-PBZI, A-366,833, ABT-202, Sympathomimethies, ABT-239, ABT-418, Almotriptan, BD-1008, LR-132, BD-1031, Singma Agonists, BD-1018, 4-PPBP, Alazocine, BD-1052, Butinoline, Clemizole, CPHPC, Desoxy-D2PM, Citalopram, Ditolyguanidine, Escitalopram, Fluoxetine, Fluvoxamine, Tgmesine, L-697,384, PRE-084, S33005, SA-4503. Siramesine, Venlafaxine, Clonidine, VUT-8430, UR-AK49, Moroxydine, Altinicline, Anabasine, 3-Bromocytine, Bradanicline, Cotinine, Desformylflustrabromine, Dianicline, DMPP, Epibatidine, Epiboxidine, Lobeline, Myosmine, PNU-120,596, PNU-282,987, ABT-089,Rivanicline, RJR-2429, Phantasmidine, Sazetidine A, SIB-1553A, TC-1698, TC-1827, TC-2216, Tebanicline, 2,3,4,5-Tetrahydro-1,5-Methano-1H-3-Benzazepine, UB-165, Varenicline, FE-β-CPPIT, FB-β-CPPIT, RTI-336, NVP-AUY922, Pleconaril, RTI-177, RTI-371, Calea Ternifolia, African Dream Herb, Ambutonium Bromide, Hyoscamine, Ilex Guayusa, Abediterol, Aclidinium Bromide, Benzilycholine Mustard, Bevonium, Bornaprine, Cyanodothiepin, Darifenacin, Dexetimide, Dicycloverine, Etybenzatropine, Fenpiverinium, Fesoterodine, Homatropine, Hydroxyzine, Imidafenacin, Ipratropium Bromide, Methylatropine, Methylhomatropine, Octatropine Methylbromide, PD-0298029, PD-102,807, Pipenzolate, Piperidolate, Tiotropium Bromide, Anisodine, Benacytazine, Butylscopolamine, CAR-226,086, CAR-301,060, CAR-301,196, Caramiphen, Clidinium Bromide, Ditran, EA-3167, EA-3443, EA-3580, EA-3834, JB-318, JB-336, Methylscoplamin Bromide, Oxapium Iodide, Oxitropium Bromide, Polyfothine, Propiverine, Pyrrobutamine, Timepidium Bromide, Tridihexethyl, Tropatepine, WIN-2299, Amrutanjan, Abstral, Acetylmethadol, Acetyldihydrocodeine, Alletorphine, Anilopam, Axomadol, BC Powder, Befiradol, Benorilate, Betamethadol, Bicifadine, Butinazocine, Carbazocine, Celadrin, Chlorodyne, Cinchophen, Co-dydramol, Co-codamal, Cogazocine, Conolidine, Deltorphin I, Dezocine, Dimepheptanol, Dipyrocetyl, TRPV1 Receptor, Capsazepine, Dosulepin, Electroanalgesia, Epideral Steroid Injection, Eptazocine, Equianalgesic, Efazocine, Fedotozine, Filenadol, Fioricet, Fiorinal, Frakefamide, Hemprenorphine, 3-HM, Ibazocine, Levallorphan, Levomepromazine, Lufuradom, Magnesium Salicylate, Blue Prickly Poppy, Menabitan, A-40174, Dimethylhepylpyran, Metamizole, Metkefamide, Moramide, Morphiceptin, Moxazocine, Nafoxadol, Malmexone, Naproxen, Nefopam, Nimesulide, Naracymethadol, Norlevorphanol, Norpipanone, NS-11394, Panadol, Penthox Inhaler, Phenacetin, Phenazone, Phenazopyridine, Propyphenazone, Proxorphan, Resiniferatoxin, Rimazolium, Romifidine, RUB-A535, Salecylamide, Salonpas, Tectin, Tolfenamic Acid, Tenazocine, Ufenamate, Volazocine, Xylazine, Yangonin, Zinda Tilismath, Ziconotide, Anazocine, Bremazocine, Cyclazocine, EKC, Fluorophen, Gemazocine, Ketazocine, Metazocine, Quadazocine, Azocine, Benzazocine, 0-2545, DOU-216,303, Phenylethylpyrrolidine, GR-89696, HA-966, ICI-199,441, ICI-204,448, NNN, Nornicotine, Clemastine, PF-03654746, RTI-229, SB-269,970, U-50488, U-69,593, Bombesin, Bivaracetam, Cebaracetam, DEABL, Cromakalim, Doxapram, Dupracetam, Etiracetam, Fasoracetam, Imuracetam, Levetiracetam, Lidanserin, Nebracetam, Nefiracetam, Nicoracetam, Oxiracetam, Piperacetam, Seletracetam, MOPPP, MPBP, MPHP, MDPDP, MDPPP, Pyrovalone, a-PBP, a-PPP, Neuropeptides, Galanin, Neuropeptide Y, Enkephalin, Somatoslatin, CCK, Substance P, Neurotensin, TRH, Acepramazine, Aceprometazine, Acetanisol, Acetohexamide, Acetophenazine, Acetophenone, Acetosyringoine, 2-Acetylpyridine, Adrenalone, Anthrone, Apocynin, Avobenzone, Benzbromarone, Benziodarone, Benzoin, Butaperazine, CB-13, AM-6545, AZ-11713908, WIN-54,461, JWH-200, WIN-56,098,S-796,260, AM-1220, AM-1221, AM-1241, AM-2233, AM-630, AAI’s, CPE, GW-405,833, JWH-193, JWH-198, JWH-007, 3-Acetyl-6-Methoxybenzaldehyde, Aflobazole, AR-A000002, Azasestron, Bazinaprine, 3-Benzhydrylmorpholine, BML-190, Cobicistat, CYT387, Desmethylmoramide, Dioxaphetyl Butyrate, Edivoxetine, Epelsiban, Demoxytocin, Carbetocine, WAY-267,464, Atosiban, Eprobemide, L-371,257, L-368,899, Quinagolide, Terbutaline, 2CB-ind, 5-APDI, APICA, Donepezil, ICI-118,551, Indatraline, Indinavir, Ladostigil, Mutisianthol, PNU-99,194, S-15535, TAI, Zicronapine, Aleglitazar, Thromboxame Receptor Agonist, Verruculogen, Brevianamide, 2,5-DKP, Fellutanine, Phenylahistine, Plinabulin, Rugulosuvine, Fedrilate, Fenbutrazate, L-733,060, G-130, HC3, Indeloxazine, Levomoramide, Metostilenol, Molindone, Molracetam, Nimorazole, O-1057, O-1812, AM-2232, O-774, AM-2389, HHC, HU-243, Canbisol, Nabilone, 11-OH-THC, 2-AGE, Paxahexyl, THC-C4, AMG-36, AMG-41, AM-1235, AM-906, AM-365, O-2694, O-2372, O-2113, O-2050, VCHSR, TM-38837, PiplSB, PF-514273, MK-9470, LY-320,135, O-2545, PD-128,907, PF-219,061, ABT-670, ABT-742, UK-414,495, OSU-6162, Melanotan II, Oxaflozane, PF-592,379, 2-Phenyl-3,6-Dimethylmorpholine, Pramocaine, SCH-50911, 4-HTMPIPO, A-41988, AB-001, AB-005, ADBICA, AM-087, AM-411, KM-233, AM-679, AM-694, AM-855, AM-905, AM-919, AM-4030, AM-938, AM-251, AMG-1, AR-231,453, PSN-375,963, PSN-632,408, (C6)-CP-47,497, CCH, O-1871, CP-55,940, CP-47,497, CP-50,556’1, CP-55,244, Otenabant, (C9)-CP-47,497, CBS-0550, AVE-1625, GW-842,166x, HU-308, HU-336, HU-331, HU-320, Ajulemic Acid, JTE-7-31, A-834,735, MDA-19, S-444,823, JTE-907, JWH-015, JWH-019, JWH-030, JWH-047, JWH-048, JWH-051, JWH-057, JWH-081, SLV319, 2-Isopropyl-5-Methyl-1-(2,6-dihydroxy-4-nonphenyl)cyclohex-1-ene, HU-345, JWH-098, JWH-116, JWH-120, JWH-122, JWH-147, JWH-148, JWH-149, JWH-161, JWH-164, JWH-167, JWH-175, JWH-176, JWH-184, JWH-185, JWH-196, JWH-203, JWH-249, JWH-302, JWH-307, JWH-359, JWH-398, JWH-424, L-759,633, L-759,656, GW-405,833, Leelamine, NESS-0327, NESS-040C5, NMP-7, Nonabine, O-1125, O-1238, O-1269, O-806, O0823, Org-27569, Org-28312, LBP-1, Org-28611, Otenabant, Perrottetinene, PF-03550096, RCS-4, RCS-8, Rosonbrant, SDB-001, SDB-006, SER-601, Serinolamide A, THC-O-Phosphate, Tinabinol, VDM-11, Virohamine, A77636, Adafenoxate, Adapromine, Adatanserin, Bolmantalate, Bromantane, SR-142,948, 25B-NBOMe, 25I-NBMB, 25TFM-NBOMe, 5-MeO-NBpBiT, 2CBCB-NBOMe, 25CN-NBOH, Juncosamine, TCB-2, 6-Br-APB, Agelferin, Cridazepam, Meta-DOB, NGD-4715, Nicergoline, P7C3, SB-357,134, Sclerotia Truffle, 5-Flouro-aMT, 6-Flouro-aMT, Telepathine, AMDA, Amperozide, Cinaserin, Deramciclane, Fenanserin, Flibanserin, Glemanserin, Iferanserin, KML-010, LY-367,265, Pruvanserin, Rauwolscine, Setoperone, Spiperone, Volinanserin, Xlamidine, Altropane, ATI-2042, PIA, RTI-121, RTI-353, Tramethinib, SB-258,585, Lu-AE58054, MS-245, Ro04-6790, SB-271,046, SB-399,885, RTI-55, AC-262,356, 2′-Acetoxycocaine, Bemestron, Benzoylthiomethylecogine, Brasofesine, 2-CMT, Clobenztropine, Cocaethylene, Deptropine, Dichloropane, Diflouropine, Granisetron, 3-(p-Flourobenzoyloxy)tropane, p-ISOCOC, Methylvanillylecogonine, Norcocaine, NS-2359, RTI-126, WF-23, WF-33, WF-31, WF-11, BRL-46470, RTI-112, RTI-113, RTI-120, RTI-150, RTI-171, RTI-274, RTI-31, RTI-32, RTI-51, RTI-83, Thiophenyltropanes, MAT Inhibitor, Salicylmethylecgonine, Tesofesine, Troparil, WIN-35428, Amfonelic Acid, Oxolinc Acid, Tropisetron, Zatosetron, Dichloropane, RTI-336, RTI-126, Tropoxane, Poyo (Palm Wine), Tropicamide, Caffetin, Formic acid, Monocled Cobra, Sisa, Tramadol, Dazopride, Dolasetron, Amylocaine, Articaine, Bupivacaine, Butacaine, Chloroprocaine, Cyclomethycaine, Etidocaine, Hexylcaine, Levobupivacaine, Mepivacaine, Meprylcaine, Prilocaine, Proxymetacaine, Risocaine, Ropivacaine, Tetracaine, Trimecaine, Piperocaine, Metabutoxycaine, Adipiplon, Almitrine, ARRY-520, AZD5423, Cisapride, CP-226,269, CRL-40,941, DBL-583, Dexamethasone, DFMD, Methyldopa, Carbidopa, d-DOPA, L-DOPS, Octaflourocyclobutane, DFB, Didesmethylcitalopram, Elopiprazole, Phenylpiprazine, F-15,599, FGIN-127, Fletazepam, Flucindole, GR-159,897, LY-503,430, MPPF, PEPA, RS-127,445, S-23, SHA-68, SNAP-7941, SNAP-94847, TP-003, TPA-023, UH-301, Calycosin, Flavinoids, Psi-Tectorigenin, Blochanin A, Formononetin, Glyciten, Irigenin, Methoxyisoflavone, 5-O-Methylgenistein, 7-O-Methylluteone, Ononin, Pratensein, Prunetin, Retusin, Tectoridin, Tectorigenin, Barbigerone, Daidzein, Derrubone, Genistein, Ipriflavone, Irilone, Luteone, Orobol, Psuedobaotigenin, Wighteone, AMG-3, Nabazenil, Naboctate, a-Napthoflavone, 11-Nor-9-Carboxy-THC, Pirnabine, Apiol, Dillapiol, 1,3-Benzodioxole, Piperonal, beta-Asarone, Eleicin, Homovanyllyl Alcohol, Myristicin, 2-Bromo-4,5-Methylenedioxyamphetamine, Californidine, Chavicine, Cinoxacin, Dibutylone, Fenoverine, Befuraline, MDIP, MDMAI, MDPR, MDAL, ORTHO-MDA, MDP1P, MDP2P, Omiloxetine, Osemozotan, Piclozotan, Robalzotan, Ebalzotan, Sarlzotan, Piperine, Protokylol, Isoprenaline, Rhoeadine, MDMPEA, MMDPEA, MMDMPEA, MDIP, MDHOET, MDPL, GYKI-52895, Ungiminorine, NADA, Methylene blue, ECG, EGCG, EGC, Levonantradol, Cone Snail Venom, A-836,339, Abacavir, CYP-LAD, 2-Bromo-LSD, BU-LAD, DAM-57, DAL, Epicriptine, Ergometrine, Ergometrinine, Ergostine, ETH-LAD, LEA-32, Methylergometrine, MLD-41, LSP, LSH, MIPLA, PARGY-LAD, PRO-LAD, DCG-IV, DOV-102,677, MDCPM, MNTX, Amfonelic acid, J-113,397, SB-612,111, VUF-6002, DBM, Piberatine, Ilercimide, Dithranol, Divaplon, Ebastine, Flopropione, Iloperidone, Ketorolac, Melperone, NNC-38-1044, Tetralone, Cuscohydrine, Hygrine, 4-NEMD, Aceburic Acid, Amfecloral, Aprobarbital, Arfendazam, Benzobarbital, Benzylbutylbarbituate, Brallobarbital, Brophebarbital, Buthalitol, Carbubarb, Climazolam, Cyclobarbital, Cyclopentobarbital, and Acid (i.e. regular LSD).

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