November 19, 2016
[00:00] Introduction/ Health IQ
[03:07] Introduction to this Episode
[04:41] About Daniel Schmachtenberger
[09:24] Daniel's Backstory
[16:51] What is Neurohacking
[20:09] What The Right Nutrients Can Do To The Brain
[32:57] Biohacks Daniel Makes Use Of
[47:05] Nootropic Compound
[55:19] Little Known Effects of Nootropic Compounds
[59:32] Neuro Vitamin and Nootropics
[1:06:00] Clinical Research on Their Products
[1:14:45] Neuro Minerals
[1:18:05] Choline Donors
[1:22:25] Step 1 and Step 2 of Qualia
[1:38:24] End of Podcast
Ben: Hey. What's up? It's Ben Greenfield. Prepared to have your mind blown because my guest on the episode that you're about to hear is basically the world's leading authority on smart drugs and nootropics, and how to maximize cognitive enhancement of your brain, how to upgrade your brain. So it's pretty cool stuff. I enjoyed this interview quite a bit. I think you will too.
However, as you know, it's not just a smart thing to upgrade your brain. It's a smart thing to upgrade and protect yourself with life insurance. I've got life insurance. But the fact is what a lot of people don't realize is that you can actually save a boatload of money on life insurance if you're a healthy person. So there's this company called Health IQ and they use science, and data, and research to get you a lower rate on life insurance if you cycle, or weightlift, or swim, or run, or anything like that because they have all this research that shows that people who exercise a lot have a much, much lower risk of early death. I don't have to tell you that. I'm preaching to the choir. But what happens is they negotiate with life insurance companies for you based on your health results. It's really cool.
So the way that you do this is you go to healthiq.com/ben and they'll give you a totally free quote. If you go to HealthIQ, like Health Intelligence Quotient, IQ, dot com slash Ben (healthiq.com/ben), you can learn about life insurance for physically active people, but also get that free life insurance quote. So it's a good way to protect yourself and to also take advantage of the fact that you're exercising to save some money.
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In this episode of The Ben Greenfield Fitness Show:
“One of the things we realized was that people who are dealing with chronic complex disease who are gonna have to do a lot of things and did have some complication are also dealing with decreased cognitive function, decreased energy, and some emotional difficulty that makes it hard to do what they need to do. So being able to support those areas is hugely beneficial.” “When caffeine is bound to pterostilbene, the pharmacodynamics of it are very interesting. It slows the rate of caffeine into the bloodstream and elongates the half-life pretty significantly.” He’s an expert in human performance and nutrition, voted America’s top personal trainer and one of the globe’s most influential people in health and fitness. His show provides you with everything you need to optimize physical and mental performance. He is Ben Greenfield. “Power, speed, mobility, balance – whatever it is for you that’s the natural movement, get out there! When you look at all the studies done… studies that have shown the greatest efficacy…” All the information you need in one place, right here, right now, on the Ben Greenfield Fitness Podcast.
Ben: Hey, folks. It's Ben Greenfield, and it's probably no secret that I often record podcasts with all sorts of special things circulating in my bloodstream. And today, it would be a definite doozy. I am chock full of huperzine, DHEA, curcumin, quercetin, BioPQQ, artichoke, coleus, ginkgo, taurine, theanine, centrophenoxine, citicoline, alpha-GPC, zinc picolinate, magnesium threonate, and a host of other variables that are right now lighting my brain on freaking fire, things called nootrophics. But my guest on today's show actually thinks there's a pretty big problem with this stuff, namely that the entire field, of the entire movement of nootropics, or smart drugs as some people will call them, even though there's a difference, that the entire movement has some pretty extreme reductionistic tendencies. Meaning that even though popping pills, and using biohacks, and self-quantification to make your body and your brain smarter, and despite the plethora of scientific findings focused on individual neurotransmitters, and mechanisms, and cell walls, and receptor sites, and brain flow, and blood flow, it's almost a bunch of like isolated variables, isolated single parts of the cognitive machinery. And in many cases when we look at all this stuff in isolation, there can be side effects. There can be drawbacks. There can be some deleterious impacts in other areas.
And so my guest today has a distinct focus. His focus is to somehow make all this stuff work together, how to better understand, basically, the complex dynamics between the brain and an entire metatheory of cognitive enhancement. As geeky, and nerdy, and woo-woo, and white lab coat-ish as that may seem, that's exactly what we're gonna be delving into in today's show, along with a host of information on what I would consider to be the most comprehensive nootropic stack ever made, and what actually happens to be circulating in my bloodstream and in my brain right now.
So my guest today is Daniel Schmachtenberger. And I just love that last name because any name that's multisyllabalic that I can say without butchering it, I'll take it. Daniel Schmachtenberger. I almost butchered it that time. Daniel has actually been studying health and neurology for quite some time. He was originally afflicted with some neurological and autoimmune illnesses that he'll fill us in on, but wasn't able to get 'em fixed with allopathic medicine or with complementary medicine. And so he really took a deep dive into physiology and pathology, and became a real academic of mind-body medicine, a student of mind-body medicine.
And he has a huge background now in everything from psychedelics, to nootropics, to meditation, to psychology, to all sorts of different tools for evolving states and stages of consciousness, and evolving the human cognitive experience. And he brings all of this together along with a ton of scientific research on his website, which I will link to in the show notes. It's called the Neurohacker Collective, and the specific flavor of nootropic that he has created is called Qualia. And so we're gonna delve into that and probably take the deepest dive we've ever taken into neurohacking, hacking the biology of your brain, your cognition, the problem with modern smart drugs, affecting your neurons in a very positive way, building new brain cells, and a whole lot more. So, Daniel, thanks for coming on the show, man.
Daniel: Ben, thanks for having me. It's good to be here.
Ben: Yeah. No problem. And you are down in Encinitas, California, right?
Daniel: That's correct.
Ben: I like it. The land of yoga pants. And also Navy SEALs, I suppose. It's kind of weird place, right? Navy SEALs and yoga pants.
Daniel: It is the intersection of both of those things.
Ben: You aren't wearing yoga pants and dressed up as a Navy SEAL with a trident, are you?
Daniel: That's private.
Ben: Okay. Alright. Alright. A little bit awkward, but we'll leave that to everyone's imagination. Anyways. So, Daniel, before we jump into this whole idea of nootropics, and cognitive enhancement, and the nitty gritty nuts and bolts of how to do it, I'm curious about what happened to you. Because I know you had some kind of an illness, or something that kinda led you down this road, but what exactly was going on with you?
Daniel: It's a field that I've always been interested in, the capability for us to develop human potential in general, and cognitive and psychologic potential specific, as well as just kind of the cutting edge of personalized and integrative medicine, both from the diagnostic and therapeutic sides, and with my background orientation towards whole systems, complex systems science, and integrating multiple disciplines and approaches together, like I said, that had always been an area of deep interest. But several years back, I did start having a bunch of symptoms. And when I went and got traditional diagnostics, I had both autoimmune rheumatic disease and signs of neurodegenerative process, and the specific things that I had going on did not have any kind of adequate treatment in allopathic medicine, and there wasn't even consistent success anywhere in integrative medicine.
And so, the answer for me was to just start seeking to understand what tissues were being damaged by what chemicals, what was happening in the chain in those causal cascades that lead to that happening, what could be the Tier 1 deviations from homeostasis that could lead to those kind of cascade.
And so that just meant starting to model out the systems in a more complex way where we don't silo between neurology, gastroenterology, immunology, et cetera 'cause obviously a gut-brain axis disorder can be affecting neurologic tissues. And so when we started to model that, applying complex systems ontology, a lot of really novel insights started to come about, and it led to me figuring out how to do appropriate diagnostics for myself of what was going on. I found a number of key, like what were what you would call original cause, and then also causal cascade insights, and was able to actually reverse both the disease pathology as well as the underlying causes, reverse autoimmune antibodies, et cetera, and was able to do similar things for many friends that had also had diagnoses that had no formal treatment. And this led to a series of insights about not just nootropics, or neuropsychopharmacology, but the future of medicine as a whole. How do we do a better job of understanding what health is in terms of whole system resilience, and what disease is in terms of decreased resilience and pathophysiology, and what the future of adequate integrative personalized medicine could look like.
Ben: That's a lot of big words, man. I'm curious in terms of like the specific nitty gritties. What are a couple examples of things that you did? Like when you're talking about autoimmune issues or neurological dysfunction, were you just like drinking bone broth and following like an autoimmune diet where you weren't eating night shades, and dairy, and soy? Or were you pulling like a lotta like fringe little biohacks, or I know what you call neurohacks, out? And if so, like where were just a couple of the things that you did that kinda like effected some really significant change?
Daniel: You know how sometimes you talk to integrative doctors or biohackers, it really focused on mold, or yeast, or GI parasites, or pathogens, or dysbiosis, or methylation, disorders from genetic predispositions, or HPA axis disorders, or Lyme's disease, or heavy metal toxicity. It's like how do you put all of the parts together of all forms of toxicity, all forms of deficiency, all forms of pathogenecity, code imbalance? ‘Cause you're obviously gonna treat Lyme disease in terms of actual Borrelia in the blood very differently than you're gonna treat a mucosal infection or you're gonna treat a heavy metal toxicity. And so, the key for me was actually enumerating the entire space of all the things that could be involved doing complex diagnostics across the whole space. And then rather than just kinda having a shotgun approach, have a very targeted therapy that factored exactly what was going on for me that would be totally different than what was going on for someone else that had the same disease diagnosis. Because you can have multiple different deviations from imbalance, deviations from homeostasis that can lead to the same kind (inaudible) disease disorder.
So I was doing specific kinds of treatments for mucosal infections, weird infections I had in my gut from international travel, and that was both meds. So Alinia, and Ivarmectin, and a number of kind of normal and not very common anti-parasitic, antibacterial meds, and a lot of supplements that were both addressing mucosal function, addressing infection directly. So that would be like an example of dealing with GI infection where we were dealing with other mucosal infection, like things and sinuses. Then were specific anti-infectious, and biofilm killing, biofilm breaking things that I did intranasally, a lot of IV therapies, IV chelation, glutathione, et cetera for aspects of toxicity, and ozone, ultraviolet lights for some humoral infection. So some things, but it wasn't just like all of the integrative things. It was very specifically targeted towards what order of operations make sense on what things that are here.
Ben: Right, right. That make sense. So you were not just like throwing everything in the kitchen sink at your body in some like desperate attempt to fix yourself. You were actually, I'm assuming, doing like blood and biomarker testing as you went along researching a lot of this stuff?
Daniel: Yeah. I started with comprehensive diagnostics across the whole spectrum of things that could be involved and then said, “Okay, does this make sense?” If I look at my medical history, when certain symptoms started, when I was exposed to certain things, I look at the whole landscape of biometrics now and in understanding of how causation could occur, do I kinda have a story of when these exposures likely happened, when these kind of exposures to toxins, infections, et cetera, injuries, stresses. And then if you can put a picture together, then you can get a sense of, “Okay. What would a project plan for reversing this?” Obviously if you've got some kind of, say, GI mucosal infection that is causing continuous inflammation to go into the bloodstream or allowing toxicity to go into the bloodstream, you're gonna wanna address that before trying to address the blood side most of the time. So order of operations, et cetera, that's just all things would factor if you're doing kind of comprehensive treatment.
Ben: Yeah. And I know that today we're gonna focus a lot more on kinda like the nutrient status of things, right. Like nutrients that you could put into your body to assist with the nervous system and with brain health, and with even like building new neurons and things like that. But in the show notes, I'm putting the show notes over at bengreenfieldfitness.com/neurohacker. As in, well, just like what it sounds like. Neurohacker. But that's a phrase I hadn't really heard thrown around until I heard you use it, Daniel. And I'm just curious, when it comes to this idea of neurohacking, before we delve into the nitty gritty of what kinda like a dream nootropic would look like, what exactly is neurohacking? How do you find neurohacking? What is it that your company does from this neurohacking standpoint?
Daniel: Like I said, even though I've been interested in the field of cognitive optimization for a long time, one of the things that had me do a deep dive into it when I was wrestling with some of these issues myself is that some of the symptoms I was dealing with were cognitive decline. And my background and like my whole life work being cognitively engaging things, that was more of debilitating than physical issues for sure. And since I was gonna have to try and study, and figure out an adequate approaches since one didn't exist, obviously I couldn't do that while having cognitive decline.
So my first thing that I applied the cognitive input I had to was how do I increase cognitive bandwidths. And so that was a deep dive into the study of cognitive nutrition, smart drugs, nootropics, et cetera. Again applying complex systems models, just like what, okay. So what really is being mediated by acetylcholine? What's being mediated by catecholamines? By glutamate? How do these systems interface? Et cetera. Getting out a more detailed understanding and then seeing how to support that whole process.
Now fast forward 18 years, one of the things we realized was that people who are dealing with chronic complex disease who are gonna have to do a lot of things and that have some complication are also dealing with decreased cognitive function, decreased energy, and some emotional difficulty that makes it hard to do what they need to do. So being able to support those areas is hugely beneficial for the rest of treating their pathology. But then, of course, that's just relevant for everyone. Right? Even at the other end of the bell curve, people who are looking for real optimization enhancement. And so neurohacking for us is you could almost think of it as a subset of biohacking, but also kind of a Venn diagram where we're looking at hacking the mind-brain interface. What things can we do that enhance? So we're not looking so much at athletic performance, even though that can be a positive side effect, we're looking at optimizing cognitive capability and psychoemotional state and predisposition.
Ben: Okay. Got it. So when we start to kinda like delve into the actual nitty gritty of, especially like the type of nutrients that you can put into your brain, my first question is, before we focus on individual ingredients, the thing that I'm curious about because I kinda wanna know how this works. From an acute effect, obviously when somebody takes like a handful of pills, like a nootropic, or some powder, or some tincture, or extract designed to help your brain fire better, is there an actual chronic change in brain structure? I mean, is there any evidence out there that you can do things like build new neurons, or reset your tolerance to things like caffeine, or increase the production of mitochondria or cell membranes, or anything along those lines? What can be done in the brain by putting the right nutrients into it?
Daniel: Yeah. This is a really important question. When we think about smart drugs in general, we oftentimes think about pharmaceuticals that are being used for off label purposes, like Adderall, or Ritalin, et cetera. We'll notice that we get immediate lift in certain metrics, like focus, or concentration, or something that's useful. But those lifts not only usually are not lasting, don't produce positive long-term effects, but oftentimes are producing negative long-term effects. Either because of side effects in other systems, or even the system they're affecting, they're affecting in a way that creates dependence. And the primary way to think about this is if you have a regulatory system, like say we're looking at Adderall. You have an endogenous system that's regulating dopamine levels and catecholamine levels. If I override that system through an external, an exogenous stimulus, then I'm gonna create dependence upon that exogenous stimulus. And that means downregulation. One of our fundamental goals was how do we understand how the body's and endogenous regulatory systems work, and rather than override them, work through those pathways where we can increase system resilience and robustness where if someone got off of whatever it was that they were taking that would actually have lasting positives because the underlying regulatory systems have become more robust.
So that was a core goal for us. And there's a number of ways of that happening. So you've got obviously the immediate effects that are usually gonna be neurochemical, neuroendocrine kind of effects. Changing people's levels of neurotransmitters, receptor site modulation, things like that can affect those fairly quickly. You've got medium term effects, which can come from things like decreasing inflammation and affecting the phospholipid cell membrane to have more integrity and elasticity. And then you've got longer term effects, like the ones you're mentioning where you start looking at things like neurogenesis, the development of new neurons, new neural stem cells, and synaptogenesis the development of new synapses, and both of those as a category of biogenesis, new biological structural development, increased mitochondria within cells. These are not gonna be permanent 'cause nothing's permanent and it's a continuously changing environment. Just like exercise and muscle development, it's not permanent, but it's lasting. Meaning if you aren't then damaging those structures and you're continuing to support them, there is lasting structural change.
So I would say with a tropical, or in general, one of people's goals should be how do we create short term immediate benefit we're looking for without creating meaningful side effects or downregulation, how do we upregulate the regulatory systems for lasting benefit, and how do we upregulate structure in a way that's going to produce, again, regulatory lasting benefit. When you look at things like, you've got the company Neurostem that is in late stage clinical trials for their product NSI-189 that some people…
Ben: What's it called? Neurostem?
Daniel: They're actually a boutique pharmaceutical company, and they were originally working doing neural stem cell injections for spinal cord injuries and ALS, and they started figuring out some small molecules that made stem cells proliferate. And their most famous one is a product called NSI-189, and that will probably become a pharmaceutical drug, but some people have already been using it as a nootropic. And specifically, its mechanism of action is neurogenesis. Developing more neural stem cells that increase grey matter density in the hippocampus and in other areas. And so it's been treating major depressive disorder.
Ben: And is this something that people like would get prescribed by a physician, or is this like an injection into the brain, or what is it?
Daniel: It's not something that someone would get prescribed yet because it hasn't finished FDA clearance, but it probably will.
Daniel: But this is an example of one that is actually moving down that kind of pharmaceutical path. But whether it would be used for, say, diabetic neuropathy, or anxiety, or depression, or Alzheimer's, if you can help develop endogenously more neural stem cells, that's gonna be very meaningful for lots of things. What happens to be that there are nutrients that are involved in our body's own process of doing that that can help in that direction and other kind of system modulators. So those are all things that we factor in the nootropics that we develop.
Ben: Interesting. So when we're talking about like new brain stem cells, what about for people with like TBIs, and head injuries, and stuff like that. I mean, I've got an orbital fractures, and TBIs, and concussions like they're going out of style. When you're talking about inducing new brain stem cells or neurogenesis, are you actually saying that you could potentially like heal certain areas of the brain?
Daniel: Yep. So when someone has a TBI, a mild traumatic brain injury or severe traumatic brain injury, the first thing that has to happen is to protect ongoing damage. So ongoing oxidative damage, excitotoxicity, any of the kinds of damage that can start to cascade. Whether we're talking about a head injury, or a stroke, neuroprotection is the first goal. And then beyond that, where there has been actual damage to neural networks, then we wanna see what can we do to help regenerate neural networks. And we've got nootropics like emoxypine, also known as Mexidol, that have been used pretty heavily off-label, mostly for post-stroke and other forms of traumatic brain injury.
Some of the Russian peptides, C Max, and Selank, and some of the more common nootropics like some of the racetams, and ampakines, and noopept in particular have been found very, both neuroprotective and neurogenic. And then you've got things like lion's mane, and taurine, and methyl B-12 that are all neurogenic through normal and endogenous processes. So even in the field of TBI treatment is only kind of scratching the surface of these areas. I do think in the not-too-distant future, we'll combine much better scan technologies like SPECT scans, and better QEEG, along with the normal FMRI, et cetera have a better picture of what's going on, and then have much better both protection and treatment capabilities.
Ben: Yeah. It actually is fun to self-quantify this stuff. I went down to Los Angeles and visited this place called the Peak Brain Institute and spent about a week there learning how to do neurofeedback, how to actually attach electrodes to my head and use this software in which you're basically flying a spaceship with your brain, but you are being rewarded with audio and visual cues that encourage, for example, production of alpha, or theta brain waves, or the decreased production of like fast stressful beta brain waves. And it's really interesting because I've tried this type of brain training both with and without certain nootropics circulating in my system, and there's a distinct difference, especially in the amount of like upregulated alpha or theta, and decreased beta when you use a self-quantification method like that.
Obviously not everybody's gonna have like a, whatever, a $3,000 piece of electrode and laptop they can do this with. But I mean there's even phone apps. I don't know if you've played around with 'em much, Daniel, but like the CNS Tap Test App, which just like tests your central nervous system by letting you keep track of how quickly you can tap in a 60-second time frame, or like the n-back app on the iPhone that just allows you to test like your short term memory recall. And it really is interesting that you can see a distinct difference that kinda goes above and beyond what you might get from, say, like a cup of coffee with this stuff.
Daniel: Well, here's a real fun concept there. Obviously we are starting to get quantified self-devices that are more available, which is hugely beneficial 'cause when we can link assessment insights with whatever we're doing in terms of influence, then we get much better and shorter upregulation cycles in terms of what we're doing. But we've obviously got also hardware that's becoming available. So it's not 128, or 64 EEG, but the MUSE is actually pretty neat for people being able to do neurofeedback on their own. And there's a few EEG neurofeedback devices that are starting to become commercially available, that are good enough that they're meaningful. So these are all part of what we would call the neurohacking movement, both assessment and influential tools. And you notice I'm not saying diagnostic or treatment because we're not operating within the FDA medical space, but these are all what we call neurohacking tools that are meaningful and that we appreciate.
But when you mention that you are doing neurofeedback, neurofeedback's not only helping you learn how to gain executive control of certain brain frequency states, but the reason that that can be lastingly beneficial is you start having certain states be more common, more baseline. And certain things that were common before, say anxiety, or whatever become less common, less baseline, that corresponds with structural changes. But when you're doing neurofeedback, even though you have something on your scalp, it's not doing any transcranial stim. It's just reading, and then you are using your own consciousness, you're using your own mind-brain system to do different things with your attention that actually leads to neuroplastic rewiring of the brain, including development of new neural networks. And that can happen also without EEG equipment, that can happen when someone learns how to juggle, or play drums, or any new kind of coordination task, they're actually having to develop new neural circuitry.
And now when you start mentioning adding something like nootropics in, think about what happens if we’re wanting someone to do therapy to cure PTSD, or they're wanting to do EEG neurofeedback to develop some new capabilities, what if we could give them chemistry that actually made their brain more neuroplastic first so it could more per unit/time of doing that therapy. And then we gave them other chemistry afterwards that was long-term potentiating that actually helped lock in that new learning. That's an example of sequencing. So that could look like microdosing psilocybin before and doing something like Ciltep afterwards, and you get to balance that plasticity, make your synapses more susceptible to change, and potentiation, lock in the learning in terms of effective synaptic formation. This would be an example of thinking through something kind of in a more comprehensive neurohacking way.
Ben: Yeah. That whole field of neuroplasticity, it's actually extremely interesting how you can strengthen or lessen existing neuronal pathways, or establish new neurons and new connections, which I know is actually called structural plasticity, versus like building new pathways, I think that's called synaptic plasticity. But you make a good point. Like you don't have to necessarily go out and spend thousands of Dollars on neurofeedback software. You can learn a language, you can play the ukulele, you can tackle some difficult interesting subject like take an online course of Udemy or learn how to code. And then you even mention something interesting. Even like psilocybin. That's a really interesting topic.
I've used psilocybin here and there, and I've found that when I have used it, the situations in which I've used psilocybin in moderation with responsibility and with intention has actually resulted in the formation of intense memories that are far brighter, and more clear, and more colorful than memories formed in the absence of something like psilocybin. So, yeah. I think this whole idea of neuroplasticity is very interesting. I wanna actually delve into some of the ingredients that you can put into your body to make it more neuroplastic, but also to do things like shut down brain inflammation, or provide the brain with neuro vitamins, et cetera. But before I ask you about that, I'm curious, just for fun, I was talking about neurofeedback, for example, and you mention the MUSE headband for meditation. Do you have anything that you do on a regular basis, in kinda like the tech sector, not necessarily like pills that you pop, but do you do like TDCS, or electro stim, or anything along those lines to enhance your own neuroplasticity? Any special biohacks that you use frequently?
Daniel: Yeah. I wouldn't just say for neuroplasticity, but for mind-brain, nervous system optimization comprehensively. So right where I'm sitting, like within just reach of my seat, I've got the Vielight Intranasal Transcranial Lasers. I like that technology quite a lot.
Ben: It's actually, and I'm gonna interrupt you super quickly because this is the million Dollar question, Daniel. Do you have the one that like wraps around your entire head and goes in your nose? Or are you an underachiever and you just have one that goes in your nose?
Daniel: No, no. Head and nose, both.
Ben: Oh, nice! So you have the Neuro.
Ben: Cool. That thing is amazing.
Daniel: But we have a bunch of other fun transcranial laser technologies. So this is primarily focused on increasing cellular ATP levels through specific frequencies of light, and obviously transcranial and intranasal for increasing ATP and neurons, which are obviously very energy intensive. And so I think that's a brilliant technology. There's a lot of forms of transcranial stim. Transcranial direct current is interesting. I'm very careful with it.
Transcranial alternating current is interesting, transcranial magnetic deep stim, and we've even got friends who are at the pioneering edge of transcranial ultrasound at University of Arizona. Stuart Hamerhoff's lab and a number of other places that are pioneering work with transcranial ultrasound to reverse beta amyloid and tel phosphorylation involved with Alzheimer's. So there are some of those technologies that I use regularly that are here, and there other ones that I've went mused very specifically for specific conditions, or that wouldn't be appropriate for me 'cause I don't have the things that they're needed, but we use them with other people that they are appropriate with right.
Ben: Right, right. Used appropriately, they're really amazing. For example, that Vielight device, I was speaking with a really intelligent neurosurgeon and a guy I've had on the podcast a few times named Dr. Jack Kruse, and we were talking about the use of things like intranasal light therapy, and the use of like that head band, that neuro head band. And one of the ideas behind that, and it's stimulation of the cytochrome C oxidase, I believe, is the specific area that stimulates it, is it creates a little bit of free radical production.
And so some of this stuff, it's not like you're hooked up to it 24/7. It's like that device, you're supposed to use about once every two to three days. Or like you talked about transcranial direct stimulation, the TDCS, which is often done with a headband. I've been trialing a device called the The Neuroscience made by a company called Halo, and it's a pretty intense form of magnetic stimulation that massively ramps up the activity in the motor cortex. And so it will, for example, decrease your sensitivity to discomfort during exercise when you use it prior to an exercise session, or increase your ability to be able to rip more weight off the floor during a deadlift. But you also, you're supposed to take a good 8 to 10 hours between any type of sessions with stuff like that just 'cause it's such an intense ride, so to speak, for your brain. So, yeah. Some of the stuff is interesting. You just have to use it responsibly, right?
Ben: I wanna interrupt this podcast to tell you about a few people that you need to follow on Instagram. So I’ve got a few ladies that you should follow on Instagram, whether you’re a lady you wanted to be inspired, or whether you’re a dude who wants to see ladies doing awesome things. So here they are, jot this down or write them down or go to the website that I’m gonna tell you about in a second and there be links to each of these girls. Molly Eledge. She is an amazing, beautiful specimen of a crossfit athlete who has some really inspirational posts on instagram. And there’s this girl called the Calisthenics Queen, Jessica Russian R3D Bogdanov. Bogdanov. Check her out, she has some amazing twirl in. She does all over the place like a Parkour athlete on steroids. Check out Kate Minwegen, that’s M-i-n-w-e-g-e-n, she’s an aerialist. She’s also freaking amazing and in her instagram page is off the hook. And then finally there’s this girl that is an adventurer who does like a bunch of free diving in deep water, and she’s really cool too. Her name is Ashleigh Baird.
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Daniel: For when you mentioned something that increases free-radicals, anything that is pro-oxidative is gonna increase free-radicals and so there’s a classic kind of relationship between oxidative and antioxidant herpes because you want a lot of oxidation of glucose within the cell and in particular areas appropriate to increase ATP and cellular energy, and you want to not be oxidizing cell walls and other structures. So our people wanting to increase oxidative bandwidth or increase antioxidant bandwidth within its pole, right, it’s a very dynamic homeostatic relationship between both of those and in different areas, in different tissues, and almost everything works like that whether we’re talking about pH or whether we’re talking about redox interactions, we’re not trying to just move the needle in one direction, we’re trying to increase system resilience in both direction simultaneously.
Ben: Yeah, yeah. It’s cool stuff though. A total rabbit hole compared to what I actually wanted to talk to you about today which is nootropic compounds ‘cause I know that’s kinda like your area of expertise and like I mentioned like I have a bunch of the actually brain nutrients that you helped design circulating in my body right now. I woke up this morning and I have these two bottles. One called step one and one is called step two. These stuff is called Qualia – Q-u-a-l-i-a, Qualia. And I was first introduced to this stuff and I might ask your permission for this first, Daniel, is it completely off limits for me to mention the god-pill, the black label version of this stuff?
Daniel: Obviously it’s not completely off limits because it happened.
Ben: (chuckles) Okay. Alright, so…
Daniel: The god-pill is as you were calling it, your name not ours, is basically stuff that we worked within the research lab but is not available for sale because we haven’t gone through all of the FDA and testing we need to for that, but it’s on our product right now.
Ben: Yeah. I kinda did stuff backwards meaning that I had no clue what neurohacker collective and who you were. I had no clue about this Qualia stuff that I’ll get in to in a second but someone at a random health and fitness conference that shall remain unnamed handed me this pill, and it was on a morning of a particularly difficult and rigorous day on which I was to speak, I was to do a whole bunch of signings and talks, I was to be attending a late night party that evening, and he handed me this pill, and he said that I want you to try this. I said, “what is it?” he said, “It’s the god-pill. There’s this black package and they opened it up and I’m like – Oh, you know, I’m one of those guys who if it is relatively natural, I’ll try it. And I took a quick glance at the ingredient list which was an extremely comprehensive list of mostly stuff I was relatively familiar with but I’ve not actually taken all at the same time in all these different nootropic compounds.
So I took it, and I did literally feel like, not trying to be blasphemous, god, the rest of the day. I mean, everything was firing on all cylinders. Verbal fluency, memory recall, the ability to form relationships and connections with, and understand and be empathetic to people, all sorts of super interesting effects. Even like reduced procrastination and reduced anxiety. Unfortunately, this effects stayed with me until about 4am in the morning. (chuckles) I was like, I wanna quit writing an article and go to sleep at some point, but very, very similar to almost like modafinil without actually kicking my liver into the ditch as modafinil can do. And so, that was my introduction and later on I discovered that there’s actually perhaps a slightly less intensive version of this stuff called Qualia. And so, that was I took this morning for example, one bottle that you take in the morning on an empty stomach and another bottle that you take with breakfast or food in your gut. And so, that is what I wanna delve in to into this Qualia stuff. So, in terms of Qualia, first of all, why do you call this specific nootropic blend that you make named Qualia?
Daniel: Yeah. It was a fun process when it comes to naming. Qualia is actually a term coming out of philosophy of mind, which means “the quality of what it is like to be you”. So your subjective experiences, the physical universe is made up of particles and force fields. The subjective universe is made up of qualia; thoughts, emotions, sensations. And so rather than just enhancing memory, or digit span, or arithmetic processing capabilities, we were alluding to the idea of optimizing one's experience of existing, subjective experience of existing. So if someone happens to know philosophy of mind, then they're like, “Oh, cool. They used a philosophy of mind term.” And if someone doesn't, it's just a cool sounding board that sounds kind of like quality.
Ben: Okay. Got it. Makes sense. Alright. So you've got one, two, three, four, five, six, I believe, seven different kinda like categories of nootropic stimulants in the ingredients of this formulation, and that kinda returns to, I guess, what you were talking about before how you don't wanna just focus on one specific area of brain enhancement. You wanna somehow get all the parts to interact. And so, if I could, I'd like to ask about the difference between some of these things 'cause I think some people may not understand what all needs to be in a complete brain compound. So first of all, one of the first categories that you have in here are nootropic compounds. What exactly is a nootropic compound?
Daniel: Yeah. Loosely, the term is generally used to mean some chemical that can enhance some aspect of cognitive function beyond someone's traditional baseline without meaningful side effects. So it's in contradistinction to smart drugs, which would enhance some aspect of cognitive function, but might have some side effects. Or brain nutrients, which aren't gonna enhance brain function beyond baseline, they're gonna make sure that you don't drop below baseline, or if you already are, help to bring it back up at their part of the kinda normal process. And so of course we're interested in, and neurohacking involves all of those categories, but that's a general way to think about what a nootropic is. And that term arose from the scientists that developed piracetam, which was the first racetam and kind of the beginning of the major family of chemicals. And then there are other families of chemicals; ampakines and other things that are part of what we usually think of, we think of nootropics.
Ben: Okay. So a nootropic in general isn't something like vitamin B to replace some things that you're burning through when you're thinking, or like choline, or something like that, but these are actual chemicals that would do things like assist with cell membrane formation in the brain, or cerebral profusion, or neuroendocrine regulation, or something like that?
Daniel: Something like that.
Ben: Okay. Got it. Now one of the things, I want to target a few kinda interesting nutrients that I wasn't really familiar with in your compound. And one of the things that you have as part of the nootrophic blend in here is called hordenine HCL. Am I pronouncing that correctly?
Daniel: Yes. Hordenine.
Ben: Okay. What exactly is hordenine?
Daniel: So hordenine's interesting. It is a barley grass extract. So it is actually not synthesize. It is an extracted compound. And it is a fairly selective MAOB inhibitor. And so you've probably used or at least heard of selegiline, Deprenyl, which is a fairly selective chemical MAOB inhibitor that many people have associated with life extension as well as probably one of the best nootropic smart drugs. And then there are other chemicals in that category that are newer, like rasagiline. This is a herbal version of something like that, less potent in the dosage that we use. And specifically MAO inhibitor is inhibiting an enzyme that breaks down certain neurotransmitters so the neurotransmitters can actually get across the synapse more effectively. MAOA and MAOB are going to protect different neurotransmitters more selectively. An MAOB inhibitor like this is going to protect primarily dopamine and then some of the associated catecholamines; norepinephrine, epinephrine, and phenylethylamine.
And the main reason that we include this, and we include a small dose, is phenylethylamine, which is a minor monoamine, that category of neurotransmitters, it's one of the primary active ingredients in chocolate and in blue green algae that gives the psychoactive effect. It's usually kind of a euphoric effect, but it has an extremely short half-life. And so it usually degrades in minutes. And so it's been a very common stack in the nootropic world, the neurohacking world, to stack something like hordenine. There are many other natural MAOB inhibitors, but to stack that with phenylethylamine so that it actually has a longer half-life and some of the positive psychostimulatory and euphoric effects actually last longer. And so it's also obviously gonna affect dopamine, which we're addressing through a number of ingredients and pathways. So that's the gist of that.
Ben: Okay. Okay. Got it. And in addition to that, that's blended with a bunch of other things that I think some people may have heard of before like a phenylethylamine, which is like a neurotransmitter. I know it's also known as the love drug, but it increases like euphoria, and arousal, and excitation. Phosphatidylserine is another one I think a lot of people know about as a way to like increase mental processing speed. I've talked about one that you have in there before called vinpocetine, which they actually had some really interesting research on in NFL football players to reduce, speaking of TBI, a lot of the issues with traumatic brain injury and in NFL players in a study, I think, that Dr. Daniel Amen did a couple of years ago. Huperzine, which, of course, Tim Ferriss made popular in the 4-Hour Body, and theobromine from chocolate, and DHEA which you mentioned. And then another part of that nootropic blend that you have that I wanted to ask you about is that you have a little bit of caffeine in there. It's not a lot of caffeine, but I noted that you bind the caffeine to something called pterostilbene. Why do you do that yet?
Daniel: Yeah. So we don't actually bind that. We get it from one of our partners called ChromaDex that makes a patented product called PURENERGY. PURENERGY is pterostilbene, which is the primary antioxidant in blueberries and certain other natural compounds. And they're binding that to caffeine, and specifically there are many companies that make pterostilbene. This company ChromaDex has a version of it called pTeroPure that they've got good clinical trials on showing its effectiveness as a cerebral antioxidant. It's very similar to resveratrol, pterostilbene is. A few of the reasons that it is preferred to resveratrol often is that it has a much longer half-life in the blood, and it crosses the blood-brain barrier to be a cerebral antioxidant more effectively. And when caffeine is bound to pterostilbene, the pharmacodynamics of it are very interesting.
So it slows the rate of caffeine into the bloodstream and elongates the half-life pretty significantly. It elongates the half-life of caffeine by about 25%, and as you look at multiple halvings, that means that after about six hours, you've actually got 50% more caffeine in the blood than you do from the same number of milligrams of caffeine not bound to pterostilbene, which means that you have both more of a delayed onset, more gradual [0:54:04] ______ slower and longer taper so you've got more consistent peak plasma levels of caffeine. And so we wanted something that had both a longer effect, and less of a crash afterwards, and less of a stimulatory peak, and this particular delivery mechanism for caffeine was the best one that we've found for this purpose. And you get the additional benefits of the pterostilbene, which there are many benefits of it, but primarily antioxidant is the main reason.
Ben: That's interesting. I've been genetically tested for this and I'm a fast caffeine oxidizer, which means that caffeine is typically in and out of my bloodstream pretty quickly. And that is one thing I notice about this is it seems to like lengthen the half-life of caffeine, like without me getting like the up and then the down. I'd never actually had caffeine bound to something like pterostilbene before, but really interesting effect. And for those of you who have tried caffeine all on its own, I would recommend that you what it feels like when you get it bound to this caffeine, especially if you're a fast coffee metabolizer like I am.
Before we delve into some of these other things, like neuro vitamins and choline donors that you have in here, kind of a bigger picture question for you, Daniel. What are some little known effects that something like a nootropic can have that people might not know about? I mentioned, for example, when I took that “God pill”, all of a sudden, I had zero desire to procrastinate. Like I was ready to jump in to do anything. And then for people who are procrastinating doing taxes, or writing that article, or cleaning up the desk drawer, whatever, it seems that nootropics may have an effect there. But are there other things besides limiting procrastination that are lesser known effects of nootropic compounds?
Daniel: Sure. Let me explain that procrastination is actually a really fun example because it wasn't one we intended when we were originally developing this formula. In earlier iterations of the formula, it was one of the positive side effects that we were like, “Well, that makes sense.” And it's cool, and particularly limiting procrastination on things that people found dreadful and odious, and now they had just much more emotional neutrality and focus, et cetera in them. And so this has been a very interesting process to both hypothesize what things we would expect to be effective and then see what actually shows up. And obviously it's gonna depend on the particular nootropic and the person. So, say we're looking at something like aniracetam versus phenylpiracetam, they're both gonna have increased memory, verbal fluency through their effect on acetylcholine and the NMDA complex. But aniracetam's gonna have more anxiety decreasing, anxiolytic effects, and phenylpiracetam's gonna have more psychostimulatory effects based on their effect on other receptor sites. So it depends. Huperzine A for instance, the acetylcholinesterase inhibition in it can cause lucid dreams. And so a lot of people will take that on their own, or take something like Qualia, and notice that they start having a lot more vivid and lucid dreams.
Some of the, I would say, positive side effects that we were most interested by is people feeling less emotional upset, less what they would call drama, emotional upset that really is not helpful or warranted, without feeling numb. So they actually feel more capable, more available to positive experiences, and negative feelings, like sadness around authentic things, but not being upset unnecessarily by stories they're generating because they're actually thinking more clearly. And so much of our emotional process is not the result of what's happening, it's the result of us not thinking through multiple different people's perspectives and generating negative meaning. And as someone simply able to think more quickly and more clearly, then they don't get poor thinking generating unnecessary emotional drama. And so I would say that's probably even one of the most fun experiences people have reported.
Ben: Yeah. I should know, by the way, when it comes to like vivid dreaming and lucid dreaming, I don't recommend, at least I personally wouldn't take this stuff in the afternoon because I found that it really produces a very intense wakefulness effect. What I have found is that later on in the day, after you would think it's out of your system, I still get a very intense amount of lucid dreaming and vivid dreaming on the days that I use this stuff. So you don't have to take it right before bed. For example, I know like Alpha BRAIN, for example, is a popular nootropic out there that if you take it before bed, it can cause some pretty intense lucid dreaming. But this stuff seems to cause it even if you take it in the morning.
Daniel: Yeah. Many of the compounds are gonna last in the bloodstream for a meaningful amount of time, and or they're going to affect some processes that last for a meaningful amount of time. So this particular acetylcholineterase inhibition has a meaningful half-life on it.
Ben: Yeah. Interesting. Okay. So you've got nootropic compounds, like the hordenine that we talked about, and the pterostilbene bound to the caffeine, and the vinpocetine, and the huperzine A, but then you also have these things you call neuro vitamins. What's the difference between a neuro vitamin and a nootropic?
Daniel: Like we were saying earlier, a neuro vitamin, basically we're just talking about vitamins that have some effect in the nervous system; either in converting amino acids into neurotransmitters, so specifically B6 and B6 in the phosphorylated version, pyridoxal-5-phosphate, and vitamin C are both critical for converting phenylalanine and tyrosine into dopamine, converting tryptophan into serotonin. And so these are, as per the definition of vitamin, these are that one has to get dietarily, the body can't synthesize them, and they serve some kind of cofactor role in some kind of process, some protein or chemical synthesis. So we've got vitamin D having so many important roles throughout the whole body. But particularly for the brain, things like myelin synthesis. We have a particular version of B1 called benfotiamine which has a very meaningful neuroprotective function, specifically in peripheral neurons, and a version of niacin which is another B vitamin, niacinamide, which helps with blood flow and cerebral profusion, but specifically NAD production. And B5s role in acetylcholine and adrenal hormone production, et cetera. So these are all vitamins in particular forms and doses that are oftentimes the limiting factor in some of the key processes that we're seeking to support.
Ben: Okay. Gotcha. So a lotta of like the vitamin B compounds in specific forms that I know are designed for their neuroprotective effects or their anti-inflammatory effects for neural tissue or cognitive impairment. But in addition to the vitamin B complex, I noticed you've got the vitamin D complex in there, but it's not just vitamin D. It's vitamin D in a form called microencapsulated cholecalciferol. What is that?
Daniel: So cholecalciferol just means vitamin D3. That's the scientific name for vitamin D3. And micro-rencapsulated, microencapsulation is a process in which you have some kind of chemical payload that is put in some kind of encapsulation that's designed to only break down or release at some target. So maybe it's trying to get your stomach acid, like an enteric microencapsulation, and release in the intestines, or move through a particular pH, or whatever. So it's a delivery method mechanism. And because vitamin D is a fat soluble vitamin, oftentimes it'll be actually in a fat base because for manufacturing reasons, these particular capsules are powdered then, we need to be able to take the D3, and stabilize it, and make sure that it would deliver effectively. So microencapsulation is usually something like alginate, particular extract from algae, or cellulose that's simply gonna help better absorption and delivery of that nutrient.
Ben: So it essentially helps to take a vitamin that would mostly be fat soluble and allows it to be somewhat water soluble?
Daniel: In this particular case, yes.
Ben: Okay. Interesting. Alright. So you've got your nootropics, and you've got your neuro vitamins, and then you also have something in there, like a class of compounds called neuro anti-inflammatorys and antioxidants. Obviously it's rocket science to know what an anti-inflammatory or an antioxidant would do in the brain, and some of them, they're relatively familiar, again, like quercetin, for example, which I know has some really cool neuroprotective effects, and curcumin, which I've talked about quite a bit on the show before in terms of its anti-inflammatory effects, especially for neural tissue, and DHA, and green tea extract. And even bioperine, or black pepper extract, which I know can help with the absorption and utilization of curcumin. There's one in there also though called BioPQQ. What is BioPQQ?
Daniel: Yeah. So PQQ is an active version of CoQ10. And so it has a number of important effect as a Krebs cycle intermediary and support in ATP production. And you can use CoQ10, you can use ubiquinol, or you can PQQ. They're progressively more potent for certain processes. So we're using PQQ, and BioPQQ is simply a patented brand that has had good clinical trials done on it. So in general, if there are companies that have made a nutraceutical and have patented a process on it that has strong, clinical trials already done, we will use that so that we know we have quality control and can reference the clinical trials that were done specifically. So PQQ does a number of interesting things. It's involved in recycling glutathione, it affects some growth factor, like nerve growth factor synthesis, but the primary reason that we're using, it does have anti-inflammatory effects and cytokine modulation, the primary reason is ATP support.
Ben: Okay. Got it. So you've got that in there for, specifically for ATP support. I know, for example, that's the same stuff that's in the, is it called the upgraded anti-aging formula that Bulletproof makes? The PQQ? I think that's the one that is. It's either upgraded anti-aging or…
Daniel: Their upgraded aging formula is oxaloacetate.
Ben: Okay. That's right.
Daniel: Then you have the unfair advantage, which is the BioPQQ.
Ben: Unfair Advantage. That's right. Unfair Advantage called BioPQQ. And speaking of which, I've talked about this before. Some of these names, and I love the products that Bulletproof makes. I'm a huge fan of their stuff. I use their Brain Octane, and I use their chocolate powder, and their bars, and all sorts of stuff. But also when you look at words, like catchy phrases like Unfair Advantage or I mean, heck, even “the God pill” phrase that I threw around earlier, there's definitely an eyebrow that gets raised in the scientific community with stuff like this, with claims like that. So I'm curious, in terms of like clinical research behind some of these ingredients, and specifically like combining all these greens into a cocktail like you guys are doing at Neurohacker Collective, is there actual clinical research behind this stuff?
Daniel: Yeah. Great. I wanna go up for one moment and describe the process of why we brought these particular compounds together in these doses rather than other things, and is it simply a throw-in-everything-but-the-kitchen-sink 'cause you mentioned a kind of trans reductionist, whole systems approach. The first thing we did when we were looking at development of a nootropic like this, because we were doing specific nootropic chemistry with people in an integrative medical clinical settings where we had their genetics, and we had a huge amount of blood chemistry on them, and could customize things like if they were under or over methylaters and which methylation gene mutations they had, and et cetera, this is obviously a very different process. We wanted to see could we provide some aspect of that kind of benefit at scale that is a formula. And there were some things that were so specific, like the way we would address the folate cycle, and many other examples that we just really couldn't work with those axes without customized input.
But we found really happily, to kind of our surprise, that there were many things that we could work with where the people who kind of self-selected being interested in something like cognitive enhancement, we had a very high percentage of people that reported on different performative tests, responded very well. And so that's what this is. But how we started was saying, “When people are seeking cognitive enhancement, what are they really seeking?” They probably don't care about arithmetic processing or digit span by themselves. They care about a whole complex of cognitive and psychoemotional things that come together that lead to a certain set of experiential states and capabilities. So it's like how do we induce creative productive flow states neurochemically much more effectively? And so it involves focus, and concentration, and task switching, and fluid intelligence, and various aspects of memory, memory IO, and long term memory, short term memory, digit span et cetera, along with things like drive and emotional resilience without creating irritability, and anxiousness, and et cetera. So we were looking at the whole complex of what side effects are often created by some smart drugs or nootropics when people are pursuing some of the effects and once additional effects are actually needed for a synergy of being able to do really meaningful work and feel optimized in the process.
And so we started with that kind of cognitive modeling, and we looked at, for each of those psychoemotional cognitive states or capabilities, how they mapped the underlying physiology, what's known about which neurotransmitters, which hormones, which underlying aspects of neural structure, et cetera are associated. And this is from any various field of integrative medicine, or neuroscience, et cetera. So we started to model out the physiological processes that mediate those capabilities, and then started to look at which chemicals affect those physiologic dynamics, and then start to explore synergies between them, and et cetera. So we developed a nootropic database of about 500 chemicals that affected the pathways we were looking at. And so when we narrowed it down to 42 in here, obviously we were including a lot of things, we're also not including a lot of things. We're including very specific [1:09:48] ______, ratios, forms.
And so most of the ingredients have clinical trials showing the specific things they do, and then we have a specific kind of process of hypothesis generation of how we are seeking to effect positive synergies, and then we've done about three years of pre-clinical data where we haven't had formal placebo control, et cetera, and we're just moving in to doing clinical trials right now. We have a partner in the neurobiology department at Stanford that's helping with it and a number of other great science partners outside of Neurohacker as well, as the team inside of Neurohacker. And so we're just engaging on our clinical trials. We're also developing an online assessment app that can assess various cognitive capabilities, like you were mentioning there's a few apps that do, but again we're going for comprehensivity, and it can assess psychostructure and psycho kind of emotional states so that people will be able to use that app to test how this is working. But also they could test anything. They could take other nootropics, they could start meditating, exercising, and just really be able to have an available resource for tracking psycho cognitive effects that are…
Ben: Right, right. So it's basically like a whole bunch of ingredients they have pretty good, robust empirical bases for support, and various degrees of laboratory and clinical research supporting their safety and their efficacy. But in terms of like putting all of this together, I mean to be frank it, sounds like it's still, you haven't actually taken this and put it through like you know double-blind, peer reviewed research quite yet. You're just kinda going off of each of the individualize ingredients.
Daniel: Yeah. Like I said, we're in the beginning of doing that, but we haven't got all the results back yet. But it'll be soon. Our first pilot trial will come back soon. What we did in the pre-clinical phase was we had several hundred people for a few years going through trials where they, again, this was not properly blinded, that they were using Quantified Mind, or Cambridge's online cognitive assessment, or various cabinet assessments like that as well as structured subjective reporting. And so we did get input on specific data on what was changing in what percentage of people, and that was enough to develop it to kind of the place that we have, and now moving into a formal clinical process.
Ben: Okay. Got it. Cool. I can speak from an n=1 experience that it seems to work quite well for me, and I suppose anyone else could try it as well. And by the way, again I'll mention the show notes, just so you guys know, I've got a fat discount on this stuff over in the show notes. Just go to bengreenfieldfitness.com/neurohacker. That's bengreenfieldfitness.com/neurohacker. Oh, go ahead.
Daniel: ‘Cause you just said n=1. This is one of the interesting things when you ask about clinical trials. Clinical trial says “does this particular chemical compound process therapy do something across some randomized database more than the placebo does”. It's a meaningful test, but obviously some people are on one end of the bell curve effect and some people are on the other end, and there's a whole bunch of variables as to why that are just statistically averaged into that bell curve. And when we're trying to do personalized medicine, or personalized optimization, where we would do something different for you than we would for anybody else, then clinical trials are not, they're still an important part of the overarching process, but they're not adequate for n=1 optimization. And so Qualia is our first product to go to market, but more personalized versions of it moving towards full-personalization, and then not just Qualia, but many different kinds of neurotechnologies coming together. Our goal is moving towards being able to do appropriate synthesis of all the biometrics and psychometrics that someone has to gain better insights into what's going on in their system and personalised optimization recommendation, which is an underlying AI problem. And so that's really what Neurohacker Collective is all about is how do we synthesize the entire space. That first, and then synthesize a space of everything that's actually meaningful to be able to affect people's cognitive, psychoemotional, mind-brain interactions. And then based on [01:14:15] ______ have about what's actually going on for them, personalize those recommendations.
Ben: Got it. Cool. I like it. I'm all about mini testing as you go through the stuff. And again, if you've got access to some of those neurofeedback software, or the MUSE headband, or n-back training, or CNS Tap Test, or anything like that, it's fun to play with this stuff in that vein as well. Neuro minerals. You have neuro minerals in there as well, like lithium orotate, and magnesium threonate, and zinc picolinate. One of the things I want to ask you about, Daniel, because I use magnesium. I've used it in the past for helping with sleep before bed, or hoping to have a nice, smooth bowel movement the next morning. You've got a form of magnesium called magnesium threonate in there. Mostly what I've used has been magnesium citrate. Why have you used magnesium threonate as your primary form of a mineral? And then kind of a bigger picture question, why minerals in general is as an inclusion in this compound?
Daniel: Yeah. So magnesium threonate is magnesium bound to threonine. And just like magnesium citrate is bound to citric acid, there's many different forms that you can bind magnesium to that will either have better or worse absorption overall, or more specific absorption targeting some of the many different things that magnesium [1:15:31] ______ . Now this would be true for any mineral, and so Magtein, which is the first kind of patented version of magnesium threonate, had very interesting and very unique trials showing increased brain levels of magnesium, specifically cerebrospinal fluid levels of magnesium that were tested in terms of double-blind placebo control. And actually for this, since we weren't testing subjective effects, they were testing specifically cerebrospinal fluid levels and placebo didn't matter that much, but testing it against other forms of magnesium and found increased elevation of cerebrospinal magnesium levels that no other form of magnesium tested had been able to show.
So when we're looking specifically at magnesium's effect for neural health, magnesium threonate seems to be the best form of magnesium currently known for increasing cerebrospinal and brain levels of magnesium. Now that doesn't mean that magnesium citrate or other forms of magnesium won't have additional benefits. We think that topical magnesium, magnesium oil is really beneficial because you've actually got rate limiting factors in terms of just GI absorption of magnesium in any form. So going through other mechanisms is good, but this one is very interesting and it seems to be from everything we know so far, unique in its neurologic benefits.
Ben: Yeah. And so minerals in general are basically to do things like modulate some of the cytokines and the eicosanoids that are created during normal neural processing. And I know there are other things that are necessary for like redox reactions, and cellular neural metabolism, and a lot of the other things you'd need minerals for, I just don't see them in a lot of nootropic compounds, and especially this form of magnesium. I'm totally on board with you. I use, in addition to the magnesium citrate that I mentioned, like a transdermal topical magnesium, especially on sore muscles. But I think it's interesting that you guys have magnesium in this compound as well.
Now not to get too nitty gritty, but I've got a couple of other questions about ingredients and then like a usage question for you. Amino acids, you have a whole broad spectrum of amino acids in there and I don't think it's much of a secret any longer that amino acids are used as neurotransmitter precursors. And so if you're low on protein, low on amino acids, especially if you're the vegan or vegetarian, I know amino acids are crucial. But then you also something in there called choline donors. Choline donors. Why is it that some would want to include a choline donor when they're taking something like a blend of amino acids, and minerals, and nootropics, and things of that nature?
Daniel: Right. So there's a number of different things we're trying to affect here. Neurotransmitters are one of the significant effects, specifically for the immediate effects and affecting things like NGF and BDNF for neurogenesis or some of the longer term effects. So there's many different pathways we're trying to effect. One of the neurotransmitters that's very meaningfully involved in memory and cognitive function is the acetylcholine pathway, and so we have various choline donors which are actually providing the choline that gets acetylated into acetylcholine. You'll notice we also have acetyl donors, both in the acetylcarnitine and the acetyltyrosine where the amino acid has its own benefit, and we're making sure that the acetyl groups aren't gonna be the rate limiting factor for acetlycholine production. And then the rest of that acetylcholine pathway involves things like, B5 is involved in the actual production of acetylcholine, the acetylcholinesterase inhibitors like huperzine A make sure that the acetylcholine in the pre-synaptic neuron can actually get across the synapse effectively, and then the NMDA modulators. So Noopept in particular, but there's a few other things increase the post-synaptic neuron's ability to receive and process the acetylcholine.
All of this is part of what we call a comprehensive acetylcholine pathway support. And the various different choline donors, so you've got citicoline, and alpha-GPC, and centrophenoxine, but also things like uridine. Uridine has a number of interesting effects. One of them is that it does convert into citicoline. We have this blend because you've got various peak plasma times, and when you want a more kind of consistent peak plasma over a long period of time, you factor that. And you've also got a kind of differential delivery where both alpha-GPC and citicoline are gonna affect peripheral nerves then centrophenoxine's effect on central nervous system. And so this is all part of what we would call acetylcholine precursors and support.
Ben: Okay. Got it. So it’s the same reason, you hear about things like choline turnover and about how you can get excessively fatigued if you try to get your brain to fire too quickly without replenishing it with things like alpha-GPC or with choline, and all you've done is you've taken a whole bunch of different forms of choline, like the cytocholine, and the centrophenoxine, and the alpha-GPC and put them all together in there so you're essentially just like covering all the choline bases, all the what would be called the cholinergic bases.
Daniel: Right. Now there's obviously many famous forms of choline like DMAE, or phosphatidylcholine, or whatever that we're not using in here for various reasons. And in the specific dosage, you'll notice that the citicholine or the alpha-GPC are lower doses than if people are using those by themselves because we're looking at the entire choline load to not make people over-cholinergic factoring all of them. So, yes. I would say it's 101 of nootropics to look at the acetylcholine pathway. And whenever someone starts to do a racetam of some kind or a racetam-like compound that's going to be a NMDA modulator for acetylcholine uptake, the first kind of principle of stacking is usually have some form of choline donor that's bound to it. So something like centrophenoxine and noopept together is a very classic stack. But then as you start to add uridine, and B5, and huperzine A, you just get a more comprehensive effect.
Ben: Right. And I know in many cases, people will like to consume a nootropic compound like this with a fatty-rich meal to help out with some of those choline precursors, and absorption in general. Like have it with eggs or have it, like in my case, with a little smoothie with some coconut milk, and seeds, and nuts. But the interesting thing, and I think kind of the unique thing about this Qualia supplement is there are two bottles that you get when you buy it. You get what's called a Step 1 and a Step 2, and only Step 2 is to be taken with food. I'm curious why'd you switch things up as far as the bottling goes and the need for Step 1 and Step 2.
Daniel: Yeah. It wasn't originally that way in terms of before it was productized and we were in development. But as you notice there, there's a lot of ingredients and there's significant quantity in a lot of the ingredients, so there's a lot of total grams. So average dose of being three of Step 1 and five relatively large tablets of Step 2. That was just what it actually took to get the kind of effect we were looking for. And so. part of the reason that we split it up has to do with GI absorptions specifically. So there's a number of compounds that actually absorb faster without food 'cause they're not competing for absorption site in the intestines and the compounds that are gonna start producing the immediate effects that people usually want to notice quickly. So most of those are in Step 1. And Step 2 are things that either absorb better with food, or could otherwise create nausea if not taken with food. And so when the whole thing was combined, you either take it all with lower absorption on the things that are in Step 1 and slower immediate kind of effects, or run the risk of nausea taking it all not with food and decreased absorption on something. So this was the best way that we could support absorption of the whole stack.
Ben: Okay. Got it. Basically the rule is on this stuff, and this the way that I've been using it. It works perfectly. I know that the dosages vary widely. You guys have dosage recommendations on your website and on the back of the bottle, but I've been taking four to five of Step 1 when I get up in the morning. And then later on, with breakfast, anywhere between, depending on the day's level of activity, three to five of the Step 2. But actually, I think it took four this morning 'cause I knew I'd be talking to you and when I talk to smart people, I need some kind of advantage to be able to keep up with you guys. So, yeah. That's interesting, the one-two combo approach.
Daniel: The doses are obviously gonna be very different based on people's sensitivity, based on their body weight, based on the desired level of effect they wanna have, based on if they have used other nootropics or stimulants, and in the past where they've actually maybe created certain kinds of dependence. So there's a lot of factors that are involved. We have a ratio that is based on if it wasn't split into 1 and 2, if it was one stack, what would it be. And so three of Step 1, and five of Step 2 represents that ratio and kind of average dosage. And people can either start there and then adjust accordingly, or if there are sensitivity concerns, start on the lowest side and then progressively move up as they feel comfortable with it. And one of the reasons you might use less of Step 2 is that many of the choline donors are in there, and there are some people that are much more sensitive to getting over-cholinergic.
And so this is one of those aspects where you really wanna get into personalization. Some people really don't need much of the choline donors at all, and other people benefit from higher doses profoundly. And so one of the things that we are working on and will be developing and releasing soon are before we get to full customization based off of genetics and clinical chemistry, we are gonna be doing kind of phenotype-specific versions that look at, in general, under or overmethylating, under or over-cholinergic, under or over-catecholaminergic, and this will provide better effect for more people. And these are still [1:16:34] ______ .
Ben: Okay. Got it. And a couple of other questions. Is this okay, like if somebody competes in like a sanctioned organization sport, like a WADA sanctioned sport, or a USADA sanctioned sport, something sanctioned by the World Anti-Doping Association, or the Olympics, or something like that, there's a whole like cocktail, a whole shotgun of stuff in here. Is it actually safe? Like is it acceptable to take if you're competing in a sport like that?
Daniel: Very possibly not. So for instance, there's a small dose of DHEA, and I know DHEA is on the banned list for a number of organizations and sports. It's fine for other organizations and sports. So this is not something that we keep an updated list on on our website. So I would say anyone who is being tested should look at what the banned list ingredients are for them, and then check to make sure this is right for them. Again, we will in the future have versions that don't have DHEA, don't have caffeine. But when we're wanting to release an initial product that would be the most well-tolerated and effective across the largest number of people, this was the best starting place. So this is not going too, as far as we would have any reason to believe, show up on any kind of illegal narcotics drug testing. There are no illegal narcotics. But as far as anti-doping, one should look into that themselves.
Ben: Yeah. I actually think it's kinda sad because like DHEA, it's not an anabolic steroid. It doesn't act like an anabolic steroid, it's free of side effects, it doesn't produce any of the negative side effects of an anabolic steroid, and I still don't understand why WADA would ban something like that that you find in freaking like raw butter, and cod liver oil, and red palm oil, and pumpkin seeds, and ghee. I mean it's kind of interesting that they would straight up and say something like that when I know they're trying to keep people from using a cocktail of potentially dangerous anabolic agents. But to me, the DHEA part of things is a bit silly. Especially when folks can wander into Walgreens and get enormous amounts of DHEA just right off the shelf and make a lot of, a lot of folks don't really realize that sometimes the Olympic anti-doping laboratories, and World Anti-Doping Agencies, and some of these agencies, they paint with a really, really broad brush, an annoyingly broad brush sometimes. So it's kinda interesting, but, oh, go ahead.
Daniel: DHEA is the precursor in terms of the endogenous steroid pathways, anabolic steroid pathways, the precursor to most of the androgens, testosterone and other androgens. And so I don't know what their process in coming up with including DHEA was, but if it was simply just saying this is part of the conversion pathway to testosterone, you can see how they would come up with it. But, yeah. I agree, especially in terms of dose dependence. We see various degrees of adrenal fatigue so commonly, and there is this pregnanolone steal preferential shunting of the precursor to both cortisol and DHEA, the hormone pregnenolone moving the cortisol whenever there is chronic ongoing stress, which is almost everyone. And so elevated cortisol to DHEA ratio is common enough, and damaging enough that some DHEA was included in the stack for general HPA support.
Ben: Yeah. Interesting. I mean I'm all in favor of it as a supplement. But like for me for example, because I know now people are like jumping to the microphones asking how I can be competing and using something that has DHEA in it with good conscience. The fact is I would never use anything that contains a bad substance leading up to a race. And in many cases you'll see that things that are banned for in-season competition, or taking right before race, or not banned for things like off-season use. So there's that consideration as well. Now obviously 42 different freakin' ingredients in this stuff.
So it kinda returns full circle to what we talked about in the very beginning, Daniel, how a big part of this is to, rather than just putting caffeine in your body, or rather just putting like modafinil in your body, or rather than just putting like coleus forskohlii, or CILTEP, or oxytocin, or any of these other things in your body, basically you're developing more of like a full systems approach. But one more kind of big picture question I have for you is it seems as though Neurohacker Collective, your website, is kind of like poised to go above and beyond just creating some kind of like a super powerful nootropic. And if you were to name like the biggest one or two things that you have coming down the pipeline that you think are going to kinda like flip the industry on its head when it comes to cognitive enhancement, is there anything in particular that you guys are developing in your deep dark secret Batman laboratories that you wanna let people know about?
Daniel: Yeah. Well, we're working both internally in terms of our own R&D department as well as externally where we work with various universities and research labs that are doing things we find really interesting to both kind of support them in their science development as well as look at synthesizing multiple technologies together. So we're working on many different technologies. Our goal in Neurohacker is to be able to curate the cutting edge of applied neuroscience through a complex systems framework and progressively support better personalization of that for all kinds of psychoneuro optimization goals for people.
And so we're working on some very interesting things in terms of delta sleep induction right now and how to increase the efficiency and effectiveness of delta sleep, working on some very interesting things in terms of how to prevent and reverse some of the brain processes that are involved in cognitive decline, and Alzheimer's, dementia, working more scalable diagnostics where people can actually be able to assess more different biomarkers and psychometrics less expensively more often to get much better quantified self data. Lots of things. Lots of things.
I would say the underlying key thing that we're working on that we're most interested in is a complex systems AI, artificial intelligence processor that can look at all of people's biometrics and psychometrics not just in regards to a specific reference range, but all of them in relationship to each other, and look at why are these biometrics the way they are in the causal relationship to other biometrics and psychometrics. What's actually causing, what are the kind of complex cascades 'cause like when you were asking about TBI earlier, someone can have an event where there's some mild traumatic brain injury from a car accident or whatever, it doesn't show up on a PET scan. They are told they don't have brain injury ‘cause it's not structural, it's functional. Afterwards, there's any number of symptoms that could occur.
So say anxiety is one of the possibilities based on which neural networks are affected, but someone could also have anxiety from a gut-brain axis disorder from a parasite or pathogen that affected their microbiome, or from a methylation disorder, or from excitotoxicity from mold. And so to us there's no such thing as anxiety in a meaningfully treatable way. There's many different pathways that can lead in to that set of overexcitatory neurologic processes, and to be able to have a better set of insights of how would you do differential diagnostics across all those things to see what is most likely to be most supportive for someone. And we're interested in the non-medical, just wellness optimizing, direct-to-consumer space, as well as the integrated medicine medical space. And we're in and deeper phases of some things, later phases of other things. But what interests us the most is not just developing specific technologies, but being able to really curate that and synthesize the entire field ongoingly, and make that otherwise unmanageable amount of information meaningfully accessible to people.
Ben: Cool. I like it. Well, the website, I will link to in the show notes. Just go to bengreenfieldfitness.com/neurohacker. If you don't know how to spell neuro, then you should probably be taking nootropics, but it's N-E-U-R-O hacker. bengreenfieldfitness.com/neurohacker. And when you go there, I'll link not only to Daniel's website, but also what I'm including in there is a supplement, a discount that you can use to get 15% off of any of these nootropic compounds, the Qualia stuff that you'll find over on Daniel's site. And I'll also into a few of the other little things that we talked about like TDCS, and the intranasal light therapy, and meditation headbands, and some of that other fun stuff you can play around with. And in the meantime, Daniel, I wanna thank you for giving your time, and coming on the show, and sharing all this incredibly interesting/mind-blowing/neuroplasticity developing information with us.
Daniel: Ben, when I mentioned that we're seeking to not only develop technologies but that to curate, synthesize them, I see that is exactly what you do. You do it through an informational framework, and also curatorial framework, and you know the whole biohacking and optimized wellness space, and I just have huge respect for the service you provide to so many people. So it was an honor to be here with you.
Ben: Well, thanks man. I appreciate it. And folks, if you're listening in, try this stuff. bengreenfieldfitness.com/neurohacker, take advantage of that very cool discount code that Daniel set up for us. And also when you go to bengreenfieldfitness.com/neurohacker, be sure to pipe in with your own questions, comments, feedback, anything you wanna contribute to the conversation, and either myself or Daniel will pitch in and reply to you. And so, until next time, I'm Ben Greenfield along with Daniel, I get to say his last name one more time, Schmachtenberger signing out from bengreenfieldfitness.com. Have a healthy week.
You’ve been listening to the Ben Greenfield Fitness Podcast. Go to bengreenfieldfitness.com for even more cutting edge fitness and performance advice.
My guest on today’s podcast believes there’s a big problem in the field of nootropics, smart drugs and cognitive enhancement: namely that the entire movement has followed some pretty extreme reductionist tendencies.
When it comes to popping pills and using biohacks and self-quantification to make your body and brain smarter, research has indeed proliferated. There is a dizzying plethora of scientific findings focused on individual neurotransmitters, mechanisms, parts of the neurotransmission cycle, cell walls, receptor sites, brain/blood flow, and hundreds of other isolated variables.
In other words, there are lots of parts and plenty of “findings” and “mechanisms.” But to date, there exists no prevailing meta-theory of the complex interactions that make up the whole of cognitive enhancement. Many various disconnected insights have so far fallen short of addressing the complex dynamics of all the interacting parts. For this reason, most nootropic, smart drug and brain biohacking products are developed to narrowly optimize one aspect of cognitive capability, only to have unexpected drawbacks, deleterious side effects and impacts on other areas.
By performing a principled meta-analysis and synthesis of existing research, we can better understand the complex dynamics and emergent homeostatic relationships within the brain and from these kinds of insights we can yield a truly advanced complex meta-theory of cognitive enhancement. Daniel Schmachtenberger, my guest on this podcast, wants to do just this.
Daniel began seriously studying health and neurology when he became afflicted with neurological and autoimmune illnesses that had no known solutions in either allopathic or complementary medicine. The insights that lead to his healing came from developing a new model for understanding physiology and pathology, which he then applied to helping many people address various forms of complex illness and optimize their capabilities beyond their previous healthy baselines.
Daniel was the academic dean for a college of mind-body medicine and has consulted for many cutting edge integrative doctors and medical clinics to help find novel solutions for complex cases. He created and ran a cutting edge think tank developing complex systems solutions for environmental and social issues, and has directed a transdisciplinary group of scholars on a philosophy of mind project addressing core questions of mind / brain interface and developed what he calls “an axiomatic reformulation for the epistemology of neuroscience”. He has a significant background with and love for psychedelics, nootropics, meditation, depth psychology, and all effective tools for evolving states and stages of consciousness and evolving the human experience.
Daniel focuses in bringing together the best scientific research on each individual mechanism and pathway supporting cognitive development, and integrating them into a whole systems view, a complex framework of integrative neuroscience and one of the most comprehensive nootropic stacks ever made called “Qualia“.
During our discussion, you’ll discover:
-What a “dream nootropic” would look like if it were to target every single component of cognitive enhancement…[16:55 & 68:45]
-How nootropics can go beyond an acute effect and actually chronically change your brain structure or “wiring”, including neuron and synapse development, increased mitochondrial ATP, healthier cell structures and increased neural complexity…[21:00 & 49:30]
-How you can actually induce the creation of new brain stem cells to heal things like traumatic brain injury, excitotoxicity and oxidative damage to the brain…[24:54]
-Two easy ways to test how your central nervous system and memory recall is responding to certain compounds you consume…[27:45]
-My personal experience with the “God pill” that Daniel developed…[42:45]
-What makes something a “nootropic” compound vs. just a nutrient or a vitamin or a smart drug…[47:00 & 59:35]
-The little-known substance know as the “love drug” that can increase euphoria and empathy…[50:18]
-A compound that can be bound to caffeine to cause caffeine to last longer without a crash…[52:20]
-The little-known effects a nootropic can have that you may not know about, such as decreased tendency to procrastinate, increased stress resilience, lucid dreaming, and beyond…[55:20 ]
-How Vitamin D delivered in a form called “Microencapsulated Cholecalciferol” can act on specific brain targets…[61:25]
-Which form of magnesium is best for neural targeting…[74:55]
-Why it’s absolutely crucial that you include something called “choline donors” when you consume a nootropic…[78:00]
-The actual clinical research behind the Qualia formulation that Daniel helped to develop, and why it must be taken as a 1-2 combo…[82:25]
-Whether this stuff safe to take if you compete in sports sanctioned by organization such as WADA, USADA, the Olympics, etc…[86:35]
-And much more!
Resources from this episode:
(use code ‘BEN15’ for 15% off any single purchase or code ‘BEN15r’ for 15% off any monthly subscription – and note that the subscriptions are already discounted 20%, so you get an additional 15% off if you spring for the subscription option!)