In the film Limitless, Bradley Cooper’s character is given a mysterious pill that transforms his mind. With this drug, he becomes a more brilliant and productive version of himself: He’s able to solve complex equations with ease and can recall anything that he’s ever seen or read. Unfortunately, the drug comes with some serious drawbacks.
We don’t have anything quite like the drug portrayed in that movie, but we do have many performance-enhancing drugs. Non-medical use of prescription stimulants like Adderall has skyrocketed in recent years. And the majority of people are using them for self-improvement – better concentration, motivation, speed-of-processing, energy, and productivity. The appeal is understandable. Most of us make our living from knowledge-based work, and we all want to be able to do better at our jobs.
So, why might this be a problem?
Well, let’s look at how Adderall works. It is a catecholamine agonist. That means that when you take Adderall, it increases the signal of the neurotransmitters dopamine and norepinephrine in the brain. It also blocks transporters that remove these catecholamines, which enables the signal to persist longer than it normally would. The effect is greater alertness and motivation, and dull tasks seem more engaging.
That’s awesome – at least in the short term. But whenever excessive numbers of neurotransmitter molecules are available to a receptor for a long time (without a cooling-off period), the body reacts by decreasing the number of receptors for that neurotransmitter. This is called receptor downregulation.
Long-term use of stimulants like Adderall eventually lead to tolerance – the same dose no longer provides the same level of mood and cognitive enhancement. Consequently, the user may have to keep ramping up the dose to get a therapeutic benefit. And there is some concern that use over time may eventually lead to more serious neurological consequences, like loss of dopamine transporters and even brain cell death.
So, amphetamines and other stimulants might a smart or sustainable strategy, especially for non-clinical cognitive enhancement (that is to say, taking the drug to do better at work as opposed to taking the drug to combat diagnosed attention deficient disorder). For a longer discussion on the use of these drugs for attention deficit disorder, listen to my conversation with the recent recipient of the lifetime achievement award from the American Psychological Association, Professor Stephen Hinshaw.
Nootropics
But there is still immense demand for chemicals that boost productivity and cognitive performance. Which brings us to nootropics. Nootropic is an umbrella term for substances that purportedly enhance cognitive functions – particularly executive function (planning, carrying out, and monitoring tasks aimed at achieving a goal), attention, and working memory, as well as non-cognitive functions like mood and motivation. However, for something to be a true nootropic it must support long-term brain health rather than producing down-regulation of receptors or substance dependence.
The hope is that nootropics might be a way to improve cognitive performance without the risk of addiction or impairment to long-term functioning that accompanies use of stimulants like Adderall. In fact, there is some inspiring evidence to suggest that nootropics may actually help keep our brains youthful and free of disease, perhaps through antioxidant and anti-inflammatory mechanisms. So nootropics might prove to be the smart choice for productivity and for health.
Guest
In this episode of humanOS radio, I talk to Daniel Schmachtenberger. Daniel calls himself a social engineer and evolutionary philosopher. He works with a group called Neurohacker Collective. Their team is dedicated to optimizing human performance.
In this interview, we discuss current research investigating human cognitive enhancement and nootropics. We also talk specifically about Qualia, a nootropic stack Daniel helped design. I presently have no financial relationship with the company or with Qualia, but I think it’s an intriguing product and I think you’ll find it interesting as well. Check out the interview below!
Last, healthy cognitive performance and cognitive enhancement are subjects that I’ve discussed previously. So, be sure to check out my articles on how exercise can enhance cognitive performance here and here, as well as my interview with Professor Marcos Frank on how sleep helps us learn and remember.
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Transcript
Dan Pardi - 00:01: Cognitive enhancement. That is the subject of today's show. The desire to boost our mental abilities is nothing new, yet the field of nootropics and cognitive enhancers is really growing rapidly. I heard a statistic on my friend Josh Trent's podcast, Wellness Force Radio, that this subject is now one of the top 10 fastest growing health trends in the world. It's not a surprise. Our world is filled with cognitive work. We are no longer tilling fields or hunting and gathering. We're in meeting rooms. We're giving presentations. We're typing code, et cetera, et cetera. We are required to spend hours upon hours focusing and performing well mentally, while at the same time being bombarded with interruptions.
00:47: If you're dubious at all that society wants the semi-equivalent of brain steroids, go back and listen to my show with Professor Stephen Hinshaw, who is the vice chair of psychiatry at UCSF, on the remarkable rise of off-label usage of stimulant smart drugs like Ritalin and Adderall. Now we have over-the-counter substances that are claiming to not only be able to enhance cognition but also be able to keep the brain healthy as we age. Oftentimes these cognitive enhancers are provided in what's called a stack, which theoretically means several complementary compounds that are combined for synergistic effect.
01:25: Today my guest is Daniel Schmachtenberger, who is the head of product at Neurohacker Collective, an organization that is dedicated to optimizing cognition and human betterment. In the show, we discuss the product Qualia, although Daniel and I are talking about ways we can work together, since we have overlapping objectives and perspectives on how to make the world a better place. I have no financial relationship with the company at the time of the recording, but I do have a favorable opinion about the product. I just want to let you know that I receive no financial remuneration from you purchasing the product because of our discussion. With that, I bring you my discussion with Daniel.
02:03: Daniel Schmachtenberger, welcome to humanOS Radio.
Daniel Schmachtenberger - 02:07: Delighted to be here. Thanks for having me.
Dan Pardi - 02:10: I have to admit, I've listened to you on several shows in preparation of today's show, and I am thrilled to have you on. I think you articulate the vision of the field that you're in probably better than anybody I've heard. This is the field of cognitive enhancement and human betterment. To begin, I'm interested to know more about you. Instead of asking the trite question of where you went to school, I'm actually curious to know more about how you developed your mind. What were the conditions under which you developed your mind as a young person and how do you continue to do that even today?
Daniel Schmachtenberger - 02:46: Fun question. I think one of the key defining things for me was I was homeschooled throughout most of my childhood. The reason for it was my parents were educational philosophers, theorists. They had the idea that if kids were given pretty much no curriculum but exposed to as many things as possible and then their interests were facilitated, that they would blossom in the unique way that they were most innately suited to. It was an educational theory experiment. I had no curriculum at all.
03:25: I never did handwriting, spelling, state capitals. It happened to be those three are good examples of things that I never learned well. Spellchecking later taught me how to spell and made the fact that my handwriting is illegible tolerable. I don't have state capitals. But I was fascinated by all of the sciences. I was fascinated by all of the philosophic disciplines. I got to start working in understanding modern physics as a little bitty kid, and Eastern and Western schools of philosophy, and et cetera. One of the other cool things was not having subject divisions, I didn't know there were subject divisions. There was no arbitrary break between physics and chemistry or chemistry and biology, or any of the disciplines.
04:15: As a little kid, I'd ask a question like, "Why is the sky blue?" Part of that answer has to do with the physics of diffraction and the molecule size in the upper atmosphere. That means you have to understand sun and stars and solar formation and atmospheric chemistry and how diffraction works and the physics of light waves and the actual molecules in the upper atmosphere, but it also means you have to understand how a retina works and what subjective blue is and what is the difference between subjective blue and objective blue and then the hard problem of neuroscience. All of that comes in to really answer that well.
04:56: Almost everything was a movement between various sciences and then getting into the deep philosophy that grounded the sciences, where the hard problems were. That led to a interdisciplinary and systems orientation to understanding the nature of reality that we live in. For me, it was always implicit that, because understanding early on evolutionary theory, the universe was going somewhere and it was organizing itself towards more orderly complexity. With that more complexity, new emergent properties with more evolved physiologies, there were new capacities of consciousness. It was clear that something like we have a role to serve in participating with that evolutionary impulsive universe.
05:51: As the one creature here that we know has the abstraction capacity with our certain structures of prefrontal cortex to understand evolution itself, to not just be a part of the grand design but be able to think about the whole thing, the direction of evolution, the principles of it, do we really have the meaningful capacity to consciously participate with it. It looked like the evolutionary impulse was evolving everything. All of the universe. My interest early was, how do I understand the universe? How do I understand where it's going and how to help participate with the evolution of everything? That also looked like activism, in terms of how to actually support the evolution of quality of life for all sentient things.
06:37: One thing I'll add, because it's so important for people to know, is that for the most part when kids ask questions that they're really interested in, like why is the sky blue, and we don't really understand the answer, we don't facilitate the interests well and then we try to force them to be interested in or at least do shit that they're really not interested in at all. The process of forcing them to do uninteresting things while not facilitating interest is what breaks people's interest in life. Then you have to extrinsically motivate them with money or reward or whatever, and otherwise they want to chill and watch TV or play video games. If people's intrinsic fascination with life gets fed and facilitated, then they are innately and ongoingly highly agentic by nature.
Dan Pardi - 07:24: Your background is particularly interesting to me. We are seriously considering homeschooling our four-year-old boy. Hearing you explain your background is motivating to me and that this is indeed a good course to pursue. I was a solid student growing up, but I became a much better student later when I found myself in learning environments where I had more freedom to do things like, for example, spend long periods of time on a subject versus changing my focus every 50 minutes like you do with most schools.
07:54: For me, changing class that frequently was really disruptive. I'm more of a type of a learner where I like to go deep. I build momentum and then I want to stick with the subject for a while. Then, also, whatever typically has my attention has all of it. I would do very well in some classes and then just okay in others. Also, the more I advanced my own education, I had the freedom to learn more about how I learn. If I knew some of these things earlier in life, my ability to advance my own knowledge with the effort I was putting in I think would have been greatly accelerated.
08:28: For my boy, Desmond, I think about how to create this custom learning experience that adaptively contours to his interests, a way to always harness that natural curiosity that we have as children and to empower that love of learning by all means necessary. It's really nice to hear about your experience and that you look back on it with appreciation.
Daniel Schmachtenberger - 08:48: Now think about this. Technologic unemployment is going to end something like 30% of all jobs in the next 15 years. It's going to start with a lot of labor jobs, but it's going to move with AI to a lot of non-labor jobs. When we think about the history of education, if a kid was going to grow up and take over the family business or the family work, whatever that was, so they had to learn how to do those things from a skill vocation point of view, or then it became more infrastructuralized and they were going to just get some job within infrastructure, within macroeconomy, they had to be prepared for the workforce.
09:32: The workforce is going to get progressively more and more automated. By the time that people who are kids now will be moving into what we called the workforce previously. What will be unique is things that are uniquely human. If there are things that robots can learn to do well and AI can learn to do well, and obviously there's a deep question around strong AI, but let's just take strong AI off for now. The things that are uniquely human are going to be the only things that are really adaptive for humans to do. They also happen to be the things that are most fascinating and fun and intrinsically rewarding for humans to do. This has always been a relevant conversation, but it is relevant in a way that it never has been right now.
Dan Pardi - 10:11: These are some big global issues that we are facing. How it's all going to play out is yet to be told. But what I'm hearing is that the need to be able to maximize some of our innate human capabilities is of paramount importance for the next generation and even for people that are going to go through this transition. When you think about a cognitive enhancer, which is ostensibly the topic of today, you think about something that might make you focus better, remember more, be able to task switch better. But if you remove a layer from there and you think this is far more important for overall humanity for us to be able to figure out ways to optimize our mind's ability to interact with this world and to be our very best on a consistent basis. What was the first experience that you had that motivated you to explore this space?
Daniel Schmachtenberger - 10:59: I've been interested in human potential development and what the space of possibility was and enhancement capabilities my whole life, whether we're talking about meditation and psychotherapy personal development, or physiology, brain chemistry. As far as chemistry goes, an interest in natural medicine and healthcare, biohacking, neurohacking, EEG, neurofeedback, these are just always hobbies. Insofar as the topics that I was really committed to for the world required high-level cognitive capacity continuously supporting that was an important topic.
11:43: I got more acutely involved when I actually was diagnosed with some mysterious autoimmune diseases that were very rapid-onset and that didn't have adequate cures in the allopathic or the holistic alternative worlds. It had a shitty prognosis. Other than physical pain, disability kinds of symptomatology, they also had decreased cognitive bandwidth symptomatology, which really was the center of abilities that didn't work for me to lose. I knew that if I was going to be able to fix these issues that didn't have adequate solutions, I was going to have to figure it out. I knew that was going to take cognitive bandwidth, so my first focus strategically was use the bandwidth that I have to focus on increasing cognitive bandwidths. Then use that to figure out the underlying pathophysiology, et cetera, of what's going on and correct it and then get back to my work.
12:47: That led to a very deep dive in the whole topic of cognitive chemistry. This was drugs, brain nutrients, nootropics, understanding neurotransmission optimization, et cetera. As I was diving deep into that space and looking at what's been done well and where there are pretty significant pulls, one of the big pulls that I'm always wanting to look at is the topic of synthesis. Where do we have a lot of knowledge of acetylcholine's role or dopamine's role or glutamate's role or neurotrophin's role, but not the complex relationship between those or even between different aspects of the regulatory system on any of them. Looking at how do we support many complex systems that are self-regulating to have increased regulatory capacity became the deep question for me, so synthesis there.
13:43: That led to me doing the kind of work on myself where I was able to actually increase cognitive bandwidth to beyond what my previous healthy baseline had been, even while I had pathophysiology going on. Then was able to figure out the underlying cause of what was going on for me, correct it, reverse autoimmune antibodies, that whole fun thing. That led to doing that with quite a few other people that had various forms of disease that didn't have adequate solution in clinical settings and to formalizing a model of how health, aging, illness, and reversal of illness could work. There was a complex, systems-informed model for medicine and well-being. That really was a lot of things that that would pertain to.
14:35: But the psychoneuropharmacology, the cognitive psychological stuff was really essential, because almost everyone who is dealing with complex illness has some brain fog cognitive effects and has some emotion affected by hearing that they've got an incurable prognoses. They have to have their psyche and their cognition in the right place to do everything that it takes to get better. Focusing on that first became a central thing. I would say that's where I went from it being a area of general interest to a area of central deep dive.
Dan Pardi - 15:14: What I'm hearing is there was a need that arose for you personally that fostered a deep dive to understand the overall system with which any possible solution would be working over your health, aging, et cetera. From there, then you wanted to understand not only how we might be able to utilize some sort of exogenous chemical to amplify a process, but rather how can we help make the entire mind that is doing the thinking stronger and better over time? It seemed like that was the goal, and then you've been working to solve that.
Daniel Schmachtenberger - 15:47: Yeah. The last thing that you said I think is absolutely central to what our goal as an organization is. Is that, when we think of psychopharmacology as a field, or really just pharmacology as a field, there are exceptions. I don't mean to overgeneralize, but generally there is less focus on fundamental causation, and especially if it is multifactorial. We focus on cause, and we're usually quite good in Western medicine if it's an acute cause. Injury or acute infection or acute poisoning is quite obvious. Then you reverse that acute cause.
16:27: If the cause is time delayed, so it's hard to find out what it was, or it's multifactorial, there are multiple things that are involved independently or multiple sequence steps, there's a causal cascade, it's hard actually to understand what it is. We'll cluster symptoms into disease names. But if we look at what was the path of the deviation from homeostasis that led to this person's MS or cancer or rheumatism, 100 different MSs have 100 different pathoetiologies. There are commonalities in them, but this is why personalized medicine is so critical.
17:07: Generally, given that understanding cause has been difficult, the focus has largely not been on what's actually imbalanced and how do we correct it, because it's not a small number of things. It's usually a large number of things. The focus has largely been, is there some kind of exogenous chemistry or treatment that we can give that will limit the symptomatology or some aspect of pathogenesis? That's better than not doing anything, but we can take the next step. Our science, et cetera, is good enough to take the next step. Our focus is, rather than give some exogenous external override to an internal regulatory system that is radically complex and intelligent and brilliant, let's work to understand what's actually wrong with the regulatory systems and/or deficient in them and upregulate the regulatory capacity of the system so that it's fundamentally more adaptive, more resilient, et cetera.
Dan Pardi - 18:07: I've done research in the condition of narcolepsy for over 10 years now. Gosh, maybe 15. I have an example that's relevant to what we're talking about. Narcoleptics are missing a protein in their brain called hypocretin. One result of that pathology is excessive daytime sleepiness, which is what usually is synonymous with the word "narcolepsy" for most people. But another symptom is called cataplexy, which is the loss of muscle tone or partial paralysis when somebody experiences emotion usually. So, Daniel, you tell me a joke, and I experience weakness in my limbs. In fact, it might be where the term "weak from laughter" comes from.
18:46: Narcoleptics also experience depression with greater frequency than the rest of the population. Early on in the treatment of this condition, narcoleptics were given a class of drugs called tricyclic antidepressants. Turns out that this medication also improves patients' cataplexy, which was totally serendipitous. But the medication is not directly confronting the cause of narcolepsy, but rather it is ameliorating one of the symptoms, but only temporarily. Here's the problem. Tricyclics do reduce cataplectic attacks in these patients, but the medication loses its potency over time. Over the course of several months, a patient will build up tolerance to the drug, and they will then need to take what's called a drug holiday to allow the receptors to resensitize to the medication.
19:26: In this scenario, however, when a patient goes off of the drug, they are essentially paralyzed for days at a time, where they're having up to 60 cataplectic attacks per day. They basically have to stay in bed until their brain resensitizes and readjusts. In some conditions, that's the best we can do. But it does highlight how when try to exogenously override, as you say, a system in the brain, usually we only provide a short-term gain, but there's always a long-term price to pay.
Daniel Schmachtenberger - 19:56: Let's take narcolepsy, for instance. What is the cause of narcolepsy? It probably has quite a few distinct causes, many of which can be happening or not in any particular situation. Can someone have sleep issues that are causing narcoleptic-like symptoms? Sure. Can they have sleep issues from structural pain somewhere in their body or from waking up in the night to urinate too much, nocturia, or from apnea or from head injury that caused firing pattern injuries or from gut-brain axis disorders or from toxicity or methylation disorders.
20:33: There's so many underlying mechanisms that can lead into a particular set of symptomatology that, in order to really be able to address is comprehensibly, our approach is identify everything that has statistical correlation that could be causal, even if it's not one-to-one correlation because we're not looking at one disease one cause. We're looking at multifactorial possibilities. Then be able to do differential diagnosis across the entire causal phase space, all the things that could be involved, to see which ones actually are. Then look at treatment that is specific to pathways rather than to symptomatology or disease clusterings.
Dan Pardi - 21:15: You're describing a very sophisticated approach to address a problem. The body is sufficiently complex that if we really want to do better with our health in the modern world, we need to be able to implement this degree of sophistication in diagnosis and in treatment. I'd like to segue to using this sort of approach to support optimized cognitive enhancement. Let's start, if you will, by describing first what is a nootropic substance for our audience, and then tell us about your product, Qualia.
Daniel Schmachtenberger - 21:48: Sure. Qualia is the first product that we've released to market. We have many other products in the neutroceutical category that are in various phases of R&D or testing and will be released soon for various different goals, mostly in the upgrading mind-brain interface space, so looking at things like pain and sleep and anxiety and et cetera. Qualia is largely what people think of as a cognitive enhancer, but the focus that we have is not adequately summarized in the word "cognitive."
22:26: Answering your first question, what are nootropics? Nootropic is a loosely defined term. There's ambiguity of the definition, but it generally means a chemical that increases some aspect of cognitive function. Maybe it's focus or memory or creativity or something, but it increases some aspect of cognitive function beyond your normal healthy baseline without meaningful side effects. We're used to things that can increase cognitive function back to baseline if you had some kind of deficit, cognitive decline or whatever. We're used to the idea of something that can be enhanced beyond baseline but with meaningfully negative side effects, like amphetamines that can increase focus.
23:17: The idea of nootropic was, can we understand some of the mechanisms that cognition operates through neurochemically and be able to support those in ways that don't create meaningful side effects or externalities. The term was coined with the development of a chemical called piracetam that really started out a whole new category of drug research, racetams, and then ampakines. Mostly they were receptor site modulators for certain neurotransmitters.
23:46: Smart drugs is a related but slightly different word which generally means pharmaceuticals that have some cognitive-enhancing potential. These are usually either drugs for narcolepsy or for ADD or for certain kinds of depression or certain kinds of neurodegen issues like Alzheimer's or Parkinson's. It would look at things like Adderall, modafinil, Wellbutrin, Depranil. These are things that can increase some aspect of cognitive baseline but oftentimes do have some meaningful consequences, so the risk-reward is a tricky thing to consider.
24:32: Nootropic is also in contradistinction to the term brain nutrient, which is just fundamental nutrients that we need dietarily and many people don't get enough of for optimum, even though they're not in acute deficiency, they're in what we call subclinical deficiency. This is the right fatty acids, the right amino acids, minerals, vitamins that support normal brain function. Those aren't going to bring you beyond baseline because the body's going to convert as many as it actually needs and then not more, but they will keep you at optimum baseline or bring you back to it if there's deficit.
25:07: Qualia actually involves key brain nutrients that are actually needed for the way some of the nootropic ingredients function. They're key cofactors or transform factors and that are chronically at suboptimal levels. Then includes some things that would be more the nootropic category, some of which are synthetic, some of which are plant-derived.
Dan Pardi - 25:33: I've been exploring the space for about a year and a half. I have to say that my own personal experience with Qualia has been very noticeable and very impressive. We've not discussed this before. For the listener, Daniel is hearing my feedback for the first time on air. My experience with Qualia has been different, I would say, than with other nootropics I tried. First, let me discuss energy. When I take it, I feel a calm energy that lasts. I don't experience a drop-off like you get with caffeine. I don't feel overstimulated either, so that's really an ideal situation.
26:11: Next, my focus is stronger with it. I feel like I can take a dip in the afternoon, though my energy doesn't necessarily flag. I still think it's just a sign that my brain wants to take a break and go for a walk, so I try to attend to that. But it's still a different feeling than simply feeling exhausted by work. Let's see. My ability to task switch is improved, which is actually a huge impact on my productivity, because in today's world there's just a lot of task switching that we all need to do with e-mail and notifications, et cetera.
26:45: Also, I'm a happy-go-lucky guy, but I even wake up in an annoyingly good mood. I actually experience a mood elevation with Qualia. How did I notice? I caught myself saying "hi" to random strangers more on the street and generally just feeling more outgoing. At first I was a little worried about this, because things that can elevate mood also are subject to a reduced mood later. But I didn't experience a dip in either the day of taking it or during the weekends when I don't take Qualia. On that note, you instruct people to take the weekend off from taking it, which I do. Again, I didn't feel the dip in energy, focus, mood, which indicates to me that what you've created really supports the health of the entire system versus trying to squeeze all the cognitive enhancement out of one pathway, leaving you feeling depleted later.
27:34: Lastly, I also noticed that I have really good sleep when I'm on Qualia. But even on the days where I don't get what I consider to be adequate amount of time in bed, so for me that's about seven and a half hours, I am less sleepy and more capable the next day when I take Qualia than I am when I don't. There you go. There's a live testimonial for you.
Daniel Schmachtenberger - 27:56: I'll share a couple things on that. First, two disclaimers on our side. One is, not a drug. Can't treat anything and it is not prescribed for any diagnosed things, et cetera. This is a supplement without FDA classification for any drug stuff. Second thing is that we are absolutely not recommending it as a way to deal with lack of sleep. As far as general lifestyle optimization goes, exercise matters, food matters, mindset matters, being outdoors matters. There's a lot of things that matter. We would probably put sleep in its own category and everything else in the second category in terms of just how important it is for overall physiology repair. One of the things that we push heavily is to really support people getting enough and good quality sleep, and that Qualia works radically better in well-rested people than in people that are dealing with some sleep deficit. Just that public service announcement.
Dan Pardi - 29:07: I agree with that fully. As a sleep researcher, there is nothing that's been identified that replaces the need for sleep. What I would say is that I think I perform better, but that does not encourage me in any way to then cheat sleep. There is a exponential benefit to getting better sleep and then Qualia in my system than getting not enough sleep on a regular basis.
Daniel Schmachtenberger - 29:28: Since you've probably talked about it a lot so your listeners know, and this is kind of common sense, if someone is getting insufficient amounts of sleep acutely rarely, then we're going to deal with that much better than chronic sleep deficit. Even if we're only talking about an hour less than the person actually needs but over a period of time, that can really start to have a profound effect.
29:56: Moving on to the effects you experience, I'm delighted because you said things related to most of the goals we had in the development of this particular product. One thing that we said was essential to our focus was how do we upregulate regulatory capacity rather than upregulate particular state in a way that then creates external dependence? We saw how many people were using Adderall not even on prescription for the appropriate purposes but off label as a way to get through midterms or finals or their tech startup or whatever.
30:34: It's a dopamine agonist, but it is, one, it's going to be flat-lining your dopamine while you're on it as opposed to having your dopamine responsive, your dopamine regulatory system responsive to what's happening, because we don't want the same dopamine levels all the time or any neurotransmitter. We want them to be responsive so our state can shift to be appropriate to the environment. Two, it's affecting dopamine without paying attention to its relationship in healthy cognitive function to acetylcholine and to so many other transmitters, and then aspects of transmission, and postsynaptic D1/D2 receptor sensitivity and et cetera. You end up getting imbalances in really key ratios and dynamics. That will end up looking like it increasing focus but not increasing key aspects of memory or even decreasing some of them or decreasing things like empathy or presence.
31:30: Then, because you are getting an exogenous override to a key in-chain chemical, it can create dependence and downregulation, ie, addiction. Our goal was the exact opposite. It was we know people weren't going to use something if they didn't feel it right away. It would just fit in a category with all their other vitamins and supplements. It had to produce the kinds of immediate effects that they were looking for, but we wanted it in a way that would not produce longterm downregulation and that would ideally produce meaningful longterm upregulation while even in the short term having a much wider scope of positive impact. Can we increase focus and concentration and short-term memory and working memory and long-term memory, creativity, analysis, synthesis all at the same time?
32:23: A lot of things that are actually almost opposite functions, like the ability to stay very focused independent of environmental noise, but then the ability to task switch when one needs to task switch are opposite kinds of functions, but we really want them both. The ability to have very high drive but also to be able to let go of it and be empathetically, interpersonally responsive when necessary, analytic and synthetic. Our focus was, can we do comprehensive brain chemistry in real time that upregulates comprehensive capacities that is also upregulating over the long term. Those were the things that we sought and we've been quite happy with what's happened so far.
Dan Pardi - 33:10: The one other component to my feedback is that, as you recommend, you take Qualia during the week and then you don't take it on the weekends. I still feel very energetic. I feel my brain is actually even smarter having taken it but not having it in my system on a weekend. That would support what your end goal was here.
Daniel Schmachtenberger - 33:30: One thing I'll say about that is, the most addictive chemical that's in this stack is caffeine. That's a chemical whose addiction curve people are pretty familiar with and is pretty benign. Everyone metabolizes caffeine differently. Some people can drink it daily for quite some time and then not drink it and be fine. Other people get headaches and it does have a lot to do with caffeine metabolism, which is genetic, and other factors.
34:08: What I'd say is, this has a relatively small amount of caffeine. We have 90 milligrams, but in the unique form where its bound to an antioxidant. The antioxidant from blueberry skins, pterostilbene, which has it basically be slow release. It feels more like 30 milligrams when it kicks on, which is very, very subtle, but then it lasts for quite some time. Instead of getting a spike and a drop-off, you get a very subtle longterm effect, which is why it's important to take in the morning, again, because it will last longer. For people who are used to drinking a big Starbucks where they've got 150 to 200 milligrams of caffeine that kicks in right away, they will still want to do that. They just might downregulate the amount a little bit, because this isn't going to match with that amount of caffeine.
34:55: On people's off days, we tell people to do five days on two days off of Qualia so that they don't desensitize to any of the chemicals that are here. On their off days, if you can't get off caffeine without headaches, you can still do your coffee or mate or whatever it is on your off days. Caffeine doesn't need cycled as frequently as other chemicals. What we'd say is, our recommendation is that people should cycle off caffeine if they use it on a daily basis for about one week per quarter so their adenosine cycle gets to reset. The other dynamics that are involved get to reset.
35:33: We do find that people will start getting decreased meaningful response from caffeine over longe periods of time. Obviously there's problems if people are using it, again, as a replacement for sleep or to push through too much fatigue when they actually need rest. If people are well-rested and they're taking appropriate amounts of caffeine, it can actually be an efficiency increasor metabolically for their system. We say two days off of Qualia each week and one week off of all stimulants per quarter.
Dan Pardi - 36:02: I was never much of a coffee drinker growing up. Several years ago, I started to drink it and it became a part of my daily routine rather fast. I enjoy my coffee with cream. I recognize that I was adding hundreds of calories to my day from my coffee routine. We know from an energy balance perspective that the body doesn't compensate for calories that are consumed in liquid form as much as it does when they're consumed in solid form. Now I get my morning boost without those additional calories. Honestly, I thought I was going to have a hard time giving up my coffee, but that's not been the case. This is another reason why I enjoy Qualia.
Daniel Schmachtenberger - 36:40: I think since Bulletproof Coffee has become as popular as it has, this is a topic few people are aware of, because they're putting a lot of calories in the form of MCT or XCT oil in there, butter. If someone's doing that and then eating the same breakfast, they're kind of missing the point.
Dan Pardi - 37:00: Exactly.
Daniel Schmachtenberger - 37:01: Most people are doing that to then not eat breakfast for quite some time or they need to downregulate the caloric intake of their breakfast.
Dan Pardi - 37:09: Exactly. I was doing the latter. What other tools do you use to either monitor your cognitive performance or to enhance it?
Daniel Schmachtenberger - 37:21: Great. Assessment wise, there are some apps that are fun. Quantified Mind is a publicly available app that anybody can use, inexpensive. Then, there are some apps that you can pay just a little bit for that have a lot of increased capacities, like Cambridge Brain Science app. There's actually two different cognitive assessments, Cambridge-associated cognitive assessments. You've got Berkeley's Greater Good Science Center has a positive psychology assessment and UPenn has some pretty great nonsymbolic experience assessments. There's a number of good online assessments.
38:13: We have a friend, Dr. Zachary Stein, who was in the education department, philosopher of education at Harvard, and worked with Howard Gardner on what was next beyond multiple lines of intelligence and I would say is one of the top theorists in developmental psychology. He and a group of friends made a assessment system called Lectica. If you go to Lectica.org you can see it, which is probably in all that I'm aware of the most advanced human cognitive psychological assessment system anywhere. It assesses for things like how complex someone's thinking is, how abstract their thinking is, levels of moral reasoning, a lot of things beyond basic psychological and cognitive assessment using really quite deep and good, involved models. Those are ones that we like and support.
39:03: We're actually working on synthesizing elements from many of those into apps that can provide better resources for people in the future as one of our goals. Those are some things. I also, as far as biometrics go, I use a lot of blood chemistry testing for biometric assessment. I'm a big fan of QEG assessment. I'm a big fan of bio-data and psycho-data, and then the key becomes the interpretive process to be able to put it together and really understand what it means and how to [crosstalk 00:39:37]
Dan Pardi - 39:37: The hard part.
Daniel Schmachtenberger - 39:38: The hard part. That's the part we're really focused on this because the data collection is getting better on the Moore's law curve. We're focused on how do you actually put all the various parts together where you're not just looking at each thing in relationship to a reference range, but each thing in relationship to all the other things to get a synergistic picture.
39:56: Then, as far as other things for cognitive performance enhancement, things I do personally, there's a lot of cognitive chemistry that I play with. Qualia is a base stack. I still, even after years with it, and having formulated it and the previous stacks that led up to it, I still use that five days a week. But for different goals, if I'm wanting to be in much more new idea creative space or much more execution-oriented space, there's some number of hundreds of other chemicals that I'll play with. Some of those chemicals will come to market. Some of them will be things that we educate people about but we could do a whole talk on nootropic chemistry sometimes.
40:46: But also, again, that's based on me knowing my actual bio-data, and then optimizing towards that. With Qualia, since we weren't able to do it in a personalized fashion to begin with, even though that's a goal for us in the future is to be able to do personalized chemistry at scale, the infrastructure for that takes quite a bit of development. We focused on what meets center of bell curve chemistry best.
41:11: Beyond chemistry for me, the other things that I will do, meditation every day is actually one of the foundational ones. Enough sleep, meditation every day, exercise that is focused specifically ... Obviously we get neurogenesis from high-intensity exercise. We get neurotrophin upregulation. The circulatory effect is important, et cetera. But new skill acquisition is huge for neurogenesis, more than anything else. New skill acquisition in the form of learning new languages, learning new musical instruments. But it seems right now that learning new motor functions, sensory coordination motor functions, has the deepest evolutionary biology on creating new neural pathways.
41:54: The key is, whenever you try and do some new activity, like say you're going to slackline or you're going to whatever that requires a kind of balance or coordination you just don't have and it seems almost impossible, your nervous system is trying to use a much larger bandwidth other than conscious processing to handle it than just conscious processing. That means driving new neurogenic circuits. Then you start to get a hang of it. As you start to get a hang of it, that effect starts decreasing. But in the process you actually increased the neural hardware for automating learning. Then you switch and do some other one.
42:32: Continuously focusing on things that are really hard until they start to become easy, and switching again, that hardware where you take new learning and automate it then translates to new cognitive and interpersonal and psychologic things that actually your rate of learning goes up. These are all things. There's many more, but those are a few examples.
Dan Pardi - 42:56: There's an approach to physical activity that I promote called InTUNE Training. It stands for integrative and opportunistic training. The goals of it are this, to support a sufficiency of physical activity in one's life, to reduce longer periods of sedentary time. Even if you're somebody who's getting a good total amount of physical activity, think of the weekend warrior concept where somebody is getting all their physical activity during the weekend but they're largely sedentary during the week, InTUNE helps you fit smaller bursts of physical activity into your days, which makes it easier to make it more regular.
43:34: One of the objectives of the program is to optimize mental performance. It does it in several ways. First, there are brain benefits to regular physical activity. Second, there are acute benefits to getting physical activity within your day, especially when you're active, your activity isn't too intense. Third, since it instructs you to do some but not a lot of physical activity day by day, you're left with a good energetic reserve. What I found is that when I do work our in this manner, I wake up with a lot of energy every single day. That is validating too the concept. Then, lastly, I also dance during the day. I try to mix in more complex movement patterns aside from just squats and pushups. This whole-body coordination supports cognitive strength. In support of that idea as well, I also have a slackline outside which I use for similar purposes.
Daniel Schmachtenberger - 44:26: Awesome. I think there are specific insights that can teach people what is optimum more like what we just talked about with the benefit of dance or slackline or balance or whatever. But most everyone knows quite a bit that they don't fully apply already, or to things like sleep and exercise and lifestyle. It's one of the things I'm most excited about with your human operating system as you continue is all of the behavioral support dynamics you're building in so that people can actually start getting traction. I'm delighted to see that continue on for you.
Dan Pardi - 45:01: Thank you, Daniel. Last question for you. What would you tell somebody who has never taken nootropics before but is curious to try them?
Daniel Schmachtenberger - 45:12: Do some research. Educate yourself. That is going to be a general MO for me in any health, well-being, performance related topic. One of the core concepts means that we hold really heavily here at Neurohacker is the topic of empowered responsibility and the idea that people take relatively little responsibility for their longevity, health, well-being, and then trust other people who don't know them that well to tell them what to do, and then have side effects and get mad at the doctors for it. It's just lame. It doesn't work. Since you're the one that lives in your body and your mind, you've just got to fucking take full responsibility for it, which you can't do it you don't understand how it works.
Dan Pardi - 45:51: Agree 100%. Well said.
Daniel Schmachtenberger - 45:54: That's the key thing that we would say, is study, learn, and then do experiments as they seem appropriate to you that you feel ready for. Of course, as part of your study, consult the appropriate people that you want to consult. You can go to our website and research how we formulated this. If you go to the formulation page, it has all the ingredients and all the research on each ingredient pathway, et cetera. Then you can try it.
46:26: It's intended as a potent nootropic stack that is relevant even for people that have a lot of experience with biohacking and neurohacking but also is one that is very good in entry fashion for many, many people. In general, if you're new to it, I would say start with the lowest dose as possible. If you don't notice them or the effect feels good but subtle, move up and titrate your way up, paying attention to your experience.
Dan Pardi - 46:56: Great advice. One thing I'll say about the experience some people have with nootropics is you might not feel it unless you're doing something that's really challenging your mind. If you take it and you're just walking around the day doing remedial tasks, you might not experience the benefit. But if you are doing something where you have to concentrate, write, code, something that is challenging your mental resources, that's where you might notice the effect.
Daniel Schmachtenberger - 47:18: One of the classic places where people report ... We didn't anticipate this upfront but it made perfect sense afterwards was people have reported in huge number ending procrastination. Specifically that things, whether it was their taxes or their desk or whatever that was normally put off a lot, that they could have sustained attention not just at things that they like but they could have sustained attention without it being unbearable, things that they had previously not liked. There was focus with better neutrality. When you say you'll notice when you actually engage it, that's one of the areas that has been really fun, people noticing when they're engaging. "Oh, shit. I actually moved the things that continuously get on my to-do list and then get moved because I never do them, and I actually did some of them."
Dan Pardi - 48:08: Daniel, this is important work. I've benefited from using Qualia. I've loved hearing your approach on how to create the very best version of a cognitive enhancer. I've been recommending it to friends when the discussion comes up on the subject. Interestingly, several of those people who have tried it have spontaneously written back to me to tell me what a positive experience they've had with it. Becoming better at getting stuff done, the stuff done that we care about, is hugely valuable. This can mean better overall work quality and it can even release you to have more free time if you can be more efficient getting your tasks done.
48:49: I believe your system thinking has really helped to develop this product and it's really paid off. I'd like to thank you for taking the time to have a conversation with me. I'm sure our listeners will appreciate the discussion. I'll be sure to put information on where people can find you in the show notes.
Daniel Schmachtenberger - 49:08: Awesome. As we continue to roll out new technologies, new products, our website is a good place to check in with it. If you feel like it, giving your e-mail, we'll definitely let people know when new things come out. We are excited to explore more partnership with you and humanOS and being able to share that as a education and training resource for people that's aligned with our goals. Thank you.
