[Transcript] - Can Weed Really Shrink Your Brain? - Ben Greenfield Life

November 21, 2015

Podcast from: https://bengreenfieldfitness.com/2015/11/can-weed-really-shrink-your-brain/

[0:00] Introduction/Harry's

[1:43] Four Sigma Foods

[3:05] Thrive Market

[4:24] Quick Message

[6:19] Dr. Andrew Hill

[12:25] Dr. Hill's Usage of THC and CBD

[15:40] THC and Brain Shrinkage

[19:54] Dealing With Addiction or Increased Tolerance to Marijuana

[39:06] Consuming Edibles

[48:27] Nootropic Compounds and Ratios

[53:56] truBrain Blend's Ingredients

[1:03:31] End of Podcast

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Last thing before we jump into today's interview. Stay tuned all the way to the end of the interview 'cause I give away some pretty sweet friggin' swag at the end of this particular show, which is about whether or not weed will shrink your brain. And no, I'm not going to send you a joint. It's something far, far better. So check it out, stay tuned to the end, and enjoy this episode.

In this episode of The Ben Greenfield Fitness Show:

“Things affect brain activity, measurable EEG activity for up to five half-lives whatever drug or substance it is. And therefore with THC, you're talking about five or six weeks of it really affecting brain activity in a chronic sense. And of course, there's acute effect on brain activity from each dose. You even sort of see it in the EEG.” “In general, the strategy for doing nootropics should be the starting place. Aniracetam and a form of choline, and uridine seems to have some of the same cell membrane upregulation effects of a cholinergic compound and affect hopefully, ultimately synthesis in acetylcholine, which is the neurotransmitter involved with memory and attention.”

Ben: Hey, folks. It's Ben Greenfield. And a couple weeks ago on a podcast episode, I talked about whether or not weed can shrink your brain. Now we spent maybe 5 or 10 minutes addressing this, but I thought it would be pretty cool to come back at you with a podcast episode in which we explore not just the effects of THC on your cognition and your brain, but also CBD, as well some other nootropics.

So my guest today is Dr. Andrew Hill. Dr. Andrew Hill has been on the show before. We had a show where we talked about smart drugs versus other herbs and the difference between smart drugs and nootropics. And Dr. Hill is a smart guy. He got his PhD in cognitive neuroscience from UCLA, studying how attention operates in the brain, he lectures at UCLA, he teaches courses on healthy brain aging, neuroscience, and psychology, he's published chapters on measuring and modulating human attention, self-regulation. And I believe Dr. Hill, as far as one aspect of your job, you actually help people at an addiction therapy clinic. Is that correct?

Dr. Hill: Yeah. Actually, I do, my primary role is as a neurofeedback practitioner where I do EEG brain measurement and assessment, and then exercising the brain using the training of the EEG, or conditioning, or biofeedback of the EEG to affect people's functional sort of status. And one of the clinics I have is attached to an addiction center in Los Angeles that has a moderation approach as well as an abstinence approach, and we do a lot of neurofeedback with those folks to affect their sort of brain status as well as doing things like mindfulness and sort of whole life coaching to help people who are struggling with, as what my partner says, “compromised relationships with substances”.

Ben: That sounds like a blast, compromised relationships with substances. I'll have try that out some time. Anyways though, one of the things that I wanted to ask you when it comes to neurofeedback, and you obviously probably use some pretty fancy expensive machines at your clinic, I would imagine, for EEG and monitoring of the brain. Do you have any opinion on a lot of these consumer devices that are popping up like? Like I know I do the HeartMath Institute has their emWave, and there's like the Muse headband. What do you think about those?

Dr. Hill: I think that HRV, heart rate variability training, which is what the HeartMath people's devices do, I think that's wonderful and really accessible, a very useful, very easy to do, I'm all in favor of HRV training. The consumer grade EEG devices are, in my opinion, vaporware entirely. They don't do what they say they do, and what they're trying to do is generally not what you want to do with EEG. There are a couple of devices that have been out for many years that don't get as much buzz because they're not little tiny wearable headbands that do actually sort of meet my criteria for consumer grade up through professional EEG for under a grand, under a thousand dollars. But that's not one of these headband devices that is flooding the market. Those things, in my opinion, are bunk and I've tested a few of the devices physically in my hands and have not been all that, well let's say I've been underwhelmed by the signal quality coming off of some of these cheap devices.

Ben: What would be an example of one of these other ones you were talking about?

Dr. Hill: So as far as I know, there's only really one company out there that has relatively low cost stuff that's actually good and they are Pocket Neurobics in Australia, and they ship worldwide. So I get a lot of my small devices, I often send people home with EEG training systems and then monitor them remotely after doing assessments with them. And I also of course do training in the clinic, and there's a four channel EEG amp that Pocket Neurobics makes called the Q-Wiz, which is about a grand. And I love it, it's a great little rugged amp, it's super easy to use. You're still pasting wires to heads and finding locations on the scalp, and so it sort of is not quite as out of the box ready as a headband. But in terms of EEG assessment, the forehead's not a great place to measure for most things. It's a really noisy area because of muscles. And if you're talking about neurofeedback, the area of the brain you typically want to start training the EEG is actually not the forehead. Frontal training can produce really bizarre and unexpected effects. And so you do a lot of your initial neurofeedback, unless there are specific focal issues that you see frontally. In general, neurofeedback is done on the central motor strip across the band of skin, if you will, from ear to ear across the top of the head. Ninety percent, I would say, of neurofeedback is done somewhere around that sensorimotor strip, and none of these headsets, these headbands dial consumer wearables, go after that area.

Ben: But this Pocket Neurobics one, does it?

Dr. Hill: Well, it's just electrodes. So you can buy silver electrodes and then you're sticking them…

Ben: Like put 'em anywhere you want.

Dr. Hill: Yeah. And so you can do one to four channels, you can paste them anywhere you like. It's not quite as idiot proof, but you have total freedom, which is quite nice.

Ben: Well, I'm looking at their website, I'll link to in the show notes for those of you who want it. It looks like it was built in 1980's, which usually means that they sell really good geeky stuff.

Dr. Hill: Right. I mean the site's really bad. But the amps are all new. Bruce McMillan who's the CEO has, he's one of the guys who chases, chases, chases improvement all the time. Kind of like you guys do. And the current version of Wiz amps is only about a year old, and it's a wonderful upgrade. He's been gradually iterating, getting better and better hardware design, and I think he sort of nailed it with the most recent version in the past year.

Ben: Sweet. I'll link to that on the show notes. For those of you listening in, the show notes for this episode are over at bengreenfieldfitness.com/weedbrain. That's bengreenfieldfitness.com/weedbrain, which brings me into the question that I want to ask you first Dr. Hill, and that is do you use, yourself, TCH or CBD?

Dr. Hill: Occasionally. Not CBD so much because, subjectively, I get no real effect from it that I can determine. The science is there for CBD and I'm sort of impressed by the breadth of effects it may have on the body and the brain, but subjectively I just don't feel CBD. So I've tried it a few times. I've tried it as an anxiolytic, I've tried it as a workout supplement. I just don't get a lot of personal benefit from CBD. I do use THC occasionally in form of smoked cannabis, smoked marijuana. I prefer the term cannabis because it's less politically charged. Marijuana was a different plant a hundred years ago. It wasn't cannabis. It's an anti-Mexican labeling in this country to call it marijuana. But I do use cannabis recreationally as well as sort of for medicinal purposes. I have a medical marijuana card in California. And for me it's not sort of a routine thing. I use it to interrupt migraines occasionally if they're creeping up. I have a pretty hardcore Ashtanga yoga practice which can leave you pretty sore, and every so often I'll use it for muscle relaxation. If I overdone it too many days in a row and I haven't hydrated enough, I get really sore of course. So I use it for sort of spot interventions, stress relief, and I will admit to using it every so often recreationally. But it does get in the way of high performance, THC itself…

Ben: Well, it can. I mean I know there are some athletes, and I've tried this myself, who will use THC, sometimes blended with CBD, to knock away some of the psychoactiveness, but basically will take that on like a trial run, for example, like 10 to 20 milligrams per hour to a trial run to get not just the pain killing effect but also a little bit more of like the runner's high. For exactly…

Dr. Hill: Sure. Absolutely, yeah. And I've certainly exercised on THC. I don't like it because I find that I have a little too much of that looseness, and high, and energy while I'm working out. And for me, Ashtanga yoga's very sort of, it's a combination of physical workout and mental meditation because you're really focusing on synchronized breath and movement, and there's no one talking at you because Ashtanga's done sort of self-paced usually. And for me, if there's THC on board, I'm a little too loose, I'm a little too bouncy, and I don't tend to drop into that meditative state. It impairs my ability to drop into meditation.

Ben: I suppose it would depend on the strain too. Whether it's like a sativa, or more of like a relaxing indica strain, or…

Dr. Hill: It doesn't affect me that way. But I'm also left ended, so I have a dramatically more sensitive brain to chemicals than most, the average human. Lefties have…

Ben: Really?

Dr. Hill: Yeah. The corpus callosum, which connects the two sides of the cortex to each other, is often dramatically thicker in lefties. The superhighway is bigger, so anything that snarls it up causes problems faster.

Ben: So left-handed people are more sensitive to like pharmaceuticals and…?

Dr. Hill: And alcohol.

Ben: Really?

Dr. Hill: Generally. I mean this is of course, there's a lot of intra-individual variability. But in general, leftie's corpus callosum is something like between 5 and 15% thicker, and therefore anything that affects that intrahemispheric transmission really affects lefties faster.

Ben: That's interesting. Now is it true that THC can shrink the brain or can decrease grey matter in the brain?

Dr. Hill: The answer, like many things in science, is it's unclear. There was some studies a couple of years ago, I think there was one in 2012, another one more recently in 2014 that said yes, that said, “Yes, there's evidence in all of these individuals that they studied that there is decreased gray matter.” Those studies, at least the one that looked like it was a little more recent, the 2014 study, showed decreases in gray matter but increases in connectivity between cells.

Ben: And just real quick, what would grey matter be exactly?

Dr. Hill: So gray matter is cell bodies. The brain is made up of neurons, and glial cells, and vasculature. Neurons have cell bodies and then these long wires that are wrapped in insulation. And the insulation is fat, it's myelin. And gray matter is the cell bodies, which you have, if you took the skull off, you would see gray because the cell bodies are in the cortex, and then axons kind of project down into the center part of the brain, they go across the midline. And so axons are part of cells. And gray matter also part of cells, white and gray matter. But the part that seems to be affected, at least in these studies, is reduced gray matter. Now I say seems because these studies are actually quite poor. They used very small numbers, I think it was like one was 35, which is not a huge number of people for this kind of stuff. There was high levels of administrations. I think they were using three times a day. They found an association of earlier time of onset in terms of youth, how much it affects the brain. So it may be more of a developmental issue and less of an actual cannabis use issue. And most importantly these early studies did not control for socioeconomic status or other lifestyle issues. So generally it's a really robust correlation if you look at the brain data. Lower SES, lower socioeconomic status does produce lower brain volume in gray matter. Increased stress, increased risk for things in the environment, decreased nutritional status, decreased educational status, all these things go along with a lower SES.

Ben: Yeah. It's kind of like the red meat cancer risk study in which you don't isolate factors. A lot of people will have a burger with a big sugary bun, and a beer, and eight cups of Dunkin' Donuts coffee.

Dr. Hill: Yeah. Exactly. All the old red meat studies that vilify red meat don't control for sugar, and we know now that in the absence of excess sugar, even saturated fats may not be unhealthful, may actually be useful for you. The same thing seems to be true in the cannabis research. All the research that shows that it decreases brain volume or has increased risks in general, they're cross-sectional studies, not longitudinal. They're not taking individuals, and giving them cannabis, and watching over time what happens to their brain. They're recruiting a half dozen or a few dozen people and taking a snapshot in time and saying that this means that chronic cannabis use affects your brain. But they're not looking at changes, they're looking at a snapshot of people who report use, but they could have already had these smaller brains. Or more likely it's related to other factors like cigarette smoking, or lower SES in general, and all the things that come along with that. So very, very weak in terms of those earlier findings.

And then this year there was a couple studies that came out, one by a guy named Wyland who did a much larger study, hundreds, like almost 300 adolescents and 500 adults, and controlled for SES, and controlled for some of these factors, and found no effect on brain volume. None. So I don't think there's actually really anything there. There's something going on in the brain, of course, when you administer THC, either acutely or chronically. But in terms of it shrinking the brain long term, I think that's more marketing than reality at this point. It's more FUD, fear, uncertainty, and doubt, than actual real science.

Ben: Okay. Now obviously there's some amount of an addictive component. Because I've heard you talk before about how you do work with people who may have either an addiction to or reduced sensitivity to marijuana in your clinic. Can you explain how that works? Like what you would do with someone who would come in and either be addicted to marijuana or perhaps need higher and higher doses to get an effect?

Dr. Hill: Let me back up and sort of actually define addiction. For something to be, for a substance to be addictive, it needs to have the properties of producing both tolerance and withdrawal. I would argue that there is no withdrawal from THC, or it's incredibly minor and does not rise to the level of an addictive substance. I would also say that the tolerance effects of THC are potentially significant, but able to be overcome fairly easily by most people just upping their consumption. So I would say that THC and cannabis in general do not actually fit the category really well of addictive substances. But that doesn't mean you can't get into trouble with, just like you can get into trouble with food, or sex, or television. You don't go into withdrawal if you don't have sex, hopefully, but you can slip into trouble with unhealthy sexual behavior, or food, or anything else that's really rewarding like high stimulus television.

And that's where I think the problem has come with THC or cannabis, it's not so much that people are developing a physiological dependence and a high level of addiction that they crave and they have to go use. I don't think that's it at all. I think what it is is these people who may develop problematic behavior with cannabis would develop in it lots of areas in their life, it just happened to be that they got into cannabis. Maybe they also have a problem sugar, or masturbation, or who knows what. It's not the same type of addictive process as like a major opiate or alcohol. And therefore, Alternatives, which is the addiction center I helped found, is all about helping you examine your relationship to things. And it's not so much the substance that's the problem, it's how you're using it. Are you using it to escape pain, or fear, or stress? Are you using it occasionally as an enjoyable recreation destressor? And this is true of all sort of low key, if you will, drugs. Alcohol used moderately is brain healthy and stress reduction focused. But if you do it chronically it's a problem. Even chronic cannabis use, wake and bake, all day long, every day does not seem to have any of the same dramatic risks that all of the other things we think about in terms of drugs of abuse. I mean no one's ever died from smoking too much weed. Ever.

Ben: Right.

Dr. Hill: Ever. I mean that's mind boggling that we hold up cannabis as this drug of abuse, and no one has ever died from cannabis intoxification. And no one's ever like smoked too much cannabis and gone on a killing spree. It doesn't produce that kind of disinhibited behavior necessarily.

Ben: Unlike alcohol or, say, antidepressants.

Dr. Hill: Right. Exactly. And there's, I think some of the confusion or the discussion, if you will, around CBD and THC long term is the fact that we don't actually know what the heck is in cannabis usually. There's all these terpenes and cannabinoids. I think the last count I saw was over 112 or something now cannabinoids identified, of which THC and CBD are among the more dominant ones that we know about and certainly the dominant ones the plant produces when it's forced to do that by the female plant being segregated from the males.

Ben: Right. Isolated from the male plant.

Dr. Hill: Yeah. That's when it produces THC. It kicks that process off. I don't think that we understand the drug, if you will, the whole plant well enough to talk about the psychoactive effects and what it might be doing beyond sort of a plethora of subjective experiences that we've been accumulating for hundreds of years, and certainly 50 years of popular culture now. But I don't think we know enough about it, and I do think that there's interesting work on CBD. But a lot of the CBD seems to affect, what is it, the CB2 receptors. So there's endogenous, or built-in receptors for internal chemicals that are very similar to cannabinoids. This is one of those interesting cases where the receptor was discovered in the body because it bound to THC, and then we went hunting for what the actual endogenous built-in signaling molecule was, and eventually found it. It's named anandamide, which is Ananda is a Sanskrit word for bliss, which is suggestive of what anandamide does inside your body.

And once we discovered THC and how it binds to these receptors, I sort of feel that science thought it had some information. But there's hundreds and hundreds of strains of THC and cannabis commercially and sort of medicinally out there now, it may have very little relationship to cannabis that was out 40, 50, 60 years ago. So I think we're sort of in a Wild West of science, and medicine, and public policy and public health. And thankfully, this is not such a horrible substance that it's going to cause the same kind of problems that alcohol caused in our culture. But it's still an open question terms of what all these things do.

Ben: So what is it that you do at your clinic if someone comes in and they seem to have an addiction or a tolerance to something like that?

Dr. Hill: Right. So at Alternatives, doctors Kern and Jaffe, who are the psychologists who work with the addiction side, I do the brain side of things there, they would examine sort of the whole person. What is your relationship with stress and living a healthy life, and what are your habits, and how do you deal with the sense of agency and being in control, and what your triggers are, and how aware are you of your triggers. And that process is the same, whether or not it's alcohol, or cannabis, or anything else. Alternatives is a little unusual in an addiction center is that it offers a moderation track as well as an abstinence track. So folks come in and say, “I'm not interested in quitting alcohol or cannabis, but I want to be in control and have a more appropriate use regimen,” so to speak. And we help them identify their triggers and cues, and there's a lot of work that goes into that, including mindfulness training and therapy, and then we do a lot of neurofeedback as well. And the process of moderation, Ben, requires tolerance to not be really high. You can't drink or smoke moderately if you don't get any effect from it. That just leads to a higher use.

So one piece about moderation is dropping tolerance. And so for alcohol, for instance, when folks go into Alternatives, they take a month off. Even if they're on moderate track, a moderation track client, they still take their first month off of alcohol. And in that time tolerance really drops and really resets, and then when they reintroduce alcohol in their lives, that it's a much more gradiated and variable experience, and they can feel the effects. We sort of have this mindful drinking approach that we help them experience the effects very differently than when they first walked in. And the same can be true of cannabis. You need to take some time off to reset tolerance. Unfortunately, the constituents of cannabis are mostly fat soluble when you smoke them or eat them, and you end up with THC and other cannabinoids bound to an unbelievable amount of tissues in the body. Basically anywhere there's adipose or lipids, THC will end up being absorbed. And so the half-life, the active half-life of, at least THC for cannabinoids, is something like five days, it drops out of your system. Well the active half-life in terms of brain is more like an hour. So an hour and a half or so, it's reducing. But in terms of measurable half-life, it's about five days, and therefore you have a very long window of activity in the brain. Things affect brain activity, measurable EEG activity for up to five half-lives of whatever drug or substance it is.

And therefore with THC, you're talking about five or six weeks of it really affecting brain activity in a chronic sense. And of course there's acute effects on brain activity from each dose. You can sort of see it in the EEG changing in the first 15, 20 minutes, and then changing again as it sort of wears off in an hour or two. So you see these things, and with cannabis, Alternatives has not had a formal cannabis moderation program because cannabis is not recreationally legal in California. So we sometimes find folks that have medical cards and are alcoholics who also smoke, or who have a problem with an opiate who also smoked marijuana, and unlike most addiction centers, we don't treat them the same way. We don't assume that any use of a mind altering substance is problematic. We look at what's going on and help them figure out where the consequences in their life are. And typically people find a way to reduce consumption of marijuana while eliminating problematic behavior, consequences, and other drugs like alcohol and opiates. People do usually take a week or two off of marijuana just to help reset tolerance, and it also helps to get a clean brain reading when there's no active drug in the system.

But over the past couple of years, I've actually just opened a brand new center in Los Angeles and I'm moving away from Alternatives, but I was there for about two and a half years, and over that time in doing neurofeedback and brain mapping on hundreds of people, I started to develop a set of neurofeedback techniques to train or exercise certain brain waves up or down and found that I can fairly dramatically actually eliminate tolerance to cannabis often in a few days. So it was a tool we started to use, if you're able to wipe someone's tolerance away, they're much more able to engage with that sort of variability of experience that is necessary for gradiating the use of a mind altering substance. And so I just sort of you know gradually discovered or developed this set of protocols that will knock tolerance down very, very quickly. This is not necessarily something magical that neurofeedback does. There's a lot of great research out there these days showing that it does a lot of things to the brain, and there's a few really interesting studies on your feedback that show that it dramatically increases plasticity. Like right after you finish training, your brain is much more likely to respond to signals into fire to change. And so I'm fairly certain that what's happening when I train the brain to reduce tolerance, but I have certain protocols, certain frequencies I'm training up in the brain. Things like beta from 15 to 18, and sensorimotor rhythm from 12 to 15 Hertz, I'm doing some…

Ben: So it's almost like you're playing the brain like a piano.

Dr. Hill: It is, actually! I'm fine tuning things, I do a snapshot of brain activity and see what's up, where certain statistical unusual patterns are, and then we exercise them up or down, or train connectivity, or differences between hemispheres. And all of those different protocols, or combinations of electrode locations and frequencies, I've developed a handful of things that worked pretty well to just wipe out the tolerance effect. And it's funny, I was discovering this effect just subjectively as I was working on people's attention, and sleep, and stress, and things like that. And it became such a robust fact that I started to warn my clients who are cannabis users, “Oh, okay client, you should be a little careful 'cause we've done a few sessions and this procedure has a tendency to dramatically reduce your tolerance. So be careful.” And then I would get sort of like, “Yeah, man. I'm an expert. I'm a professional smoker. Don't tell me how to smoke. I know what I'm doing.” And then they come back the next day, “Oh, you weren't kidding. I smoked a joint and I couldn't get off the couch, and I was drooling, and my girlfriend's mad at me now 'cause I wasn't listening to her.” And these would be like hardcore professional lifestyle smokers have their tolerance rolled back…

Ben: It's like you pushed the reboot button, almost.

Dr. Hill: It's like high school again, and the very first joint someone handed them, and they don't understand just how much that their relationship to the substance is changing.

Ben: Does the same thing happen when you're treating someone with alcohol addiction? Like will they leave a qEEG session, and have like a glass of wine, and get tipsy from that?

Dr. Hill: A little bit maybe. With alcohol, all the clients take a month off whether or not they're moderate or abstinence track for Alternatives. What happens at the end of that month when folks decide they want to reintroduce, if they decide they want to stay on moderation track and it's now time to start rebuilding a relationship, if you will, with alcohol the psychologists go to a bar with a client and we have a drink with them. Actually, they have a drink. We buy the food, they buy the alcohol. And it's I think one drink the first time we do that, a week later it's two drinks, and we sit and talk to them about their experience, they have a breathalyzer every 20 minutes, and they start of valuating their subjective experience from a specific drink, and how long it takes off, and alters them, and then wears off, and they're checking their blood alcohol volume every few minutes so they can get a sense of what blood alcohol is. So it's very structured and people don't generally have this like, “Well, I went and had a drink and I got really wrecked,” because the alcohol is such a structured program.

And it's also not so much that alcohol tolerance is reduced by neurofeedback, there's other things that show up in alcohol tolerance in the brain that I work on with the neurofeedback. The most common, most qEEG, let me break down some nomenclature for you. qEEG is an assessment technique. It's called brain mapping. We record a full head of EEG, we compare it to a database, so we take some resting baseline. So I'd have you sit here, Ben, with your eyes closed for several minutes, your eyes open for several minutes. We then take that data and compare it to a normative database that has several thousand users in it. And out of that, we get statistical maps that tell me how unusual your brain is. That's the assessment part of the picture. Based on the brain waves we see, we then start exercising them using biofeedback. We increase the amplitude, or the frequency, or the connectivity of different brain waves.

When someone comes in who has a chronic alcohol issue, like they've had a drink or two every day, or a bottle or two every day for many, many years, I see a specific acquired brain pattern problem, and that is excess high frequency brain activity, beta and fast beta activities, and dramatically increased connectivity across the whole brain in those frequencies. So the brain is locked in this really buzzy busy state, and those people cannot actually downregulate and turn off their mind at night. They don't make a lot of slow activity, like alpha and theta, and they can't calm down, there's a lot of anxiety. And so with those folks, it's not tolerance I'm affecting so much, it's this acquired a pattern from alcohol. As I'm sure you know, alcohol releases GABA in the brain, which is an anxiolytic and calming neurotransmitter. And if you're releasing your GABA every night with a large amount of alcohol, eventually your brain says, “Oh, I don't need to make GABA 'cause the alcohol is doing it for me.” And chronically over many, many years, the brain sort of stops figuring out how to downregulate and how to calm down. And so these people are just unable to fall asleep that will, unable to calm down, unable to sort of think calmly, and that's what we're doing with neurofeedback. We're tamping down all that excess beta, we're bringing up all the deep alpha and theta frequencies. And in a few weeks, yes, there is some reduction in tolerance probably from the neurofeedback, but it's really the sleep onset that we're helping them get back into, and the drop in anxiety, and the drop in sort of scattered thoughts. That's what the neurofeedback's doing for the alcohol people generally for first. For the cannabis people, it's dropping tolerance very quickly and also working on the sort of, maybe the acquired ADHD-ness that somebody came in with, either from cannabis or because they were self-medicating ADHD with cannabis, which often happens.

Ben: Okay. Interesting. So you're basically just mapping the brain, looking at areas of the brain that light up, and then hitting those areas of the brain, or any area of the brain with specific electrical frequencies designed to bring it into the state that you want to be as far as the brainwaves go?

Dr. Hill: Almost. Except we aren't hitting. There's no, we aren't zapping the brain. We're simply measuring what you're making moment to moment. So, Ben, you're making all frequencies right now, delta, theta, alpha, beta, gamma. And hopefully I'm so interesting that you're mostly making a lot of beta and I'm helping you suppress your slow brain waves, delta, theta, and alpha, because I'm just scintillating in my conversation. When we train the brain, we're measuring the moment to moment amount of all of those frequencies. And let's say, there's often a couple of target frequencies we care about. Theta is often less cognitive sort of focus, more impulsivity, distractibility. And betas often very focused, or using your mind in an efficient way. And the ratio of theta to beta is a very well-validated marker for attention problems. When someone comes in, I might look at their ratio of theta to beta, and it's a little high, I will measure that ratio moment to moment. It's going to fluctuate 'cause brains are doing lots of things, thousands of things every moment. And whenever it happens to naturally trend in the right direction, I'll make a computer, like a spaceship fly, or an audio track get louder in volume, or something else happen, and then when the brain drifts in the “wrong direction” I'll stop providing the feedback, the brain gets kind of annoyed. “Hey, wait. Where's my spaceship? Where's my Pac-Man?”

Ben: That makes sense. That's very similar to like the emWave stuff I've experimented with with heart rate variability where you'll make flowers grow on a screen to change the actual heart rate variability that you're getting. And if you're not able to consciously relax your heart, then the flowers won't grow. It's really interesting stuff.

Dr. Hill: Yeah. The only difference is in peripheral biofeedback, which is HRV, and central biofeedback, like neurofeedback, central neurofeedback is non-voluntary. So in peripheral, you must try and learn to feel the experience to work on the skill, but in central neurofeedback you simply sit there and let it happen. And over many, many days we gradually shape the brain activity further, and further, and further in one direction, and then figure out if that's the right effect for you. But neurofeedback, or EEG biofeedback, is not an effortful or voluntary process. It was discovered on animals, cats in the joke I tell is that they're notoriously bad instruction followers, and little children, non-verbal kids, people in coma. Neurofeedback works fine for people who are not cognitively intact. It still changes the brain. So it's really operating at a very low level, bottom up sort of attention system coupling to the outside world, and that's how it's shaping brain activity. Peripheral, if you don't practice peripheral, if you practice your HRV, you lose the ability to control your heart rate variability. You must practice.

Ben: Really?

Dr. Hill: Must learn what it feels like. Yeah. Peripheral biofeedback wears off.

Ben: Yeah. ‘Cause I do it every morning and my values got higher and higher for about a year. Now they seem to have kind of plateaued now, but that's interesting because that is a daily practice for me.

Dr. Hill: And if you took six months off, you would lose some of that ability. If you do a few months of neurofeedback and then stopped, your brain would be practicing its new modes all the time because you use your brain for lots of things. And so you just sort of get a built in permanence often in neurofeedback.

Ben: Okay. Got it. Now I want to ask you a few other things, especially returning to THC. When someone uses let's say, like I know you said that you smoke, and I know a lot of times when you smoke or when you vape, you get a lot of the components absorbed through like mucus membranes or through the lungs. But I know that when you eat like THC or an edible, it's metabolized in a different manner. Have you found any evidence that it is potentially damaging to the organs, like the liver, for example?

Dr. Hill: I mean I haven't. There's always, there's science in both directions when you ask a question, there's conflicting results. But it looks to me, reading the research, well, let's back up for a second. So when you swallow THC, when you eat it, it goes through the stomach obviously, and anything that hits the stomach is pulled into the bloodstream, if you will, via the liver to some extent. So the liver has what's called a first path metabolism. Breaks down anything that gets absorbed through the stomach. And cannabis is converted from one version, 9-Delta-THC into, I think, 11-Delta, or 11…

Ben: Yeah. It's like 11-Hydroxy-THC.

Dr. Hill: Yeah. 11-Hydroxy, there you go. 11-Hydroxy is a very different substance. It's still THC, but it doesn't have the same blood-brain barrier penetrance, and also the inhalation format goes directly into the brain, has very little liver activity initially. There's sort of second pass that happens, and even when you smoke it, you get some of the liver metabolism later on. But when you eat it, you get mostly liver metabolism effects, and it's a dramatically different effect. I, personally, cannot eat cannabis. At all.

Ben: What do you mean you can't?

Dr. Hill: It provokes dramatic migraines if I eat it to the point where I have like massive vertigo, and I stumble around, and can't, like I'm…

Ben: Is that because 11-Hydroxy-THC, more of that is getting into your brain than if you inhaled THC?

Dr. Hill: I have to think it is because there's such a different route of administration. I have no problem with migraines when I inhale it, and in fact I don't get migraines that often because I do neurofeedback for them. But every so often, I'll get dehydrated and have worked out twice that day, I'll get home and be like, “Oh! There some visual disturbance. Here comes a migraine.” And smoking a little bit will just shut it right down. But so will doing almost anything else that affects brain activity, like caffeine or catching dehydration early enough. But then if I eat it, I've discovered that I can just count on a migraine within the next hour or two. And I have a typical migraine. They aren't painful, they're neurological. So I do get visual disturbances or massive vertigo, and eating THC of any sort produces massive vertigo for about two days. And that's the other issue with eating is that the route of administration is different, the route of elimination is also quite different. And instead of getting effect for an hour or two like you would when you smoked or vaporized, when you eat it, it can be an effect for 10, 11, 12, 15, 20 hours.

Ben: Yeah. A lot more difficult to dose too. Sometimes you'll find like a THC edible that'll be the size of a gummy bear, it'll knock you on your butt versus a giant cookie which doesn't seem to have an effect at all. It's very interesting that how it doesn't seem to be standardized.

Dr. Hill: Exactly. And some of it probably is like the amount of fat or sugar which you're co-administering and then absorption. Some of it probably is how intact your gut lining is and can absorb things. Some of it is the kinds of food you might already have in there.

Ben: You mean like a less intact gut lining, something like leaky gut syndrome, if you were to consuming an edible with leaky gut syndrome, it would result in less of it being absorbed or more of it being absorbed?

Dr. Hill: The point I'm trying to make is that the digestion pathway, if you will, for getting things into your body is very complicated and has very many steps. The inhalation pathway, it just right into your brain. Almost instantly. So there's many more possible ways for the effect to change person to person to person if you eat it. And so that's why it's much less predictable. I have lots of friends that are medicinal and recreational users that do like edibles, and they find they have to sort of titrate a specific brand and figure out what one brand edible, what a dose means for that brand, and then use their dosing based on, “Okay, this brand I should have 10 milligrams. This brand, I can have 15. This brand, I should only have 5,” because it has different effects. And some of it's going to be the different preparation in the edible. Some of it's probably different versions of cannabis going in and…

Ben: Right. Different levels of terpenes or active compounds.

Dr. Hill: Exactly. And the terpenes, cannabinoids are terpenes and they are responsible for the flavor, and the color, and the smell, and everything else in cannabis. But there's, if you take the other terpenes beyond just simply cannabinoids, I think there's a several hundred, like 700 terepenes. And I bet we're going to find that a lot of those are psychoactive and have other ways of mediating the THC in CBD effects. And also I know a few people who have got really excited but CBD, actually one, I have a client who loves your show, and everything you say he believes. He's gone out and gotten some CBD a few different times and he gets profoundly high from it.

Ben: Really? That's interesting. ‘Cause I take CBD every day, I don't get high from it, but I also, I only take about 30 to 40 milligrams. I know some people who will take like a hundred milligrams of CBD.

Dr. Hill: I'm not sure how much he's taking, but I would guess it's not so much the dose, it's the preparation. It's not very well controlled. So you might get two different brands of CBD and one might actually have some THC in it.

Ben: Yeah. Now the stuff I use has like 0.003% THC. And I mean it has like a lab analysis that comes with it.

Dr. Hill: But you're getting into why it's important to go after an above board use of these things. I mean I'm really quite pleased that cannabis is becoming recreationally allowed everywhere because it's going to remove the issues of people getting random drugs they don't know what they're getting illegally, or getting cannabis that's full of pesticides or additions to make it taste different or have different psychoactive properties. That's sort of falling by the wayside with these proliferation of pot shops and cannabis dispensaries who do all their own internal testing and publishing broad spec sheets on all the different terpenes and things. So I'm really pleased with how people's access to the stuff is becoming data based, information bound. And that's really quite wonderful and I think that it's really important to keep an emphasis on data. And if you don't know the dose of a THC, milligrams, like I recently got some cannabis delivered, my cannabis shop delivers to my door. It's kind of nice. And there was like a free, they drop some free sample and that was honey that was infused to THC. And there was no dose on it. And I didn't like edibles anyway, so I you know didn't do it. But it concerned me that I couldn't figure out even what the dose, what the THC milligrams was. And so I think it's just, you can get into much more difficulty, you can get into places where you dosed way too much, way too easily because, I mean there's also a lag, there's a one to two hour lag from eating for the full effects versus like 10 minutes if you smoke or inhale.

Ben: That's something that I always do if I use an edible or something like that, I set my stopwatch just in case I use it again just to see how long it takes for the effects to kick in. And yeah, the minimum I've ever seen is 40 minutes before you feel something. With the exception being that if you completely dissolve using like the mucus membranes in your mouth, you can sometimes feel the effects slightly more quickly. But about 40 minutes if you just eat it would be like the minimum.

Dr. Hill: Right. Exactly. And people, I think that you can get into trouble when it's a lag of effect, when it has, instead of a couple hours of subjective effect, it can have a day of effect. I think that you're much more likely to get into trouble because you don't dose in a way that you understand.

Ben: Right, right. Yeah. I'll have to send you some CBD, some of this water soluble stuff that I use. Because from what I understand, that's one of the issues, it's mostly just fat soluble versus water soluble. So you absorb far less from a fat soluble version.

Dr. Hill: Yeah. Maybe that's why I wasn't getting, I was getting those little chewable CBD things just off of Amazon. So I probably just got a not-a-very-great one that I tried. So I'd love to try your endorsed version.

Ben: Yeah. It's in like a nanoparticle. So extremely small, very water soluble. Yeah. I want to ask you though, speaking of formulations, 'cause I know you've formulated things that go above and beyond, well I know you have been formulating THC based compounds. But you have formulated some other hair spinning type of thing. truBrain is one compound that you've helped to create. You've helped the folks over at truBrain. I want to ask you a little bit about that formulation. And I guess more specifically when it comes to smart drugs or nootropics, the ratios. And the reason I ask that, well for example, someone had sent me some tea that has like smart drug-like compounds in it, and it's like peppermint tea, and it's got some GPC and I believe some phosphatidylcholine and stuff like that. But then you guys at truBrain had sent me one of these little smart drug sticks that you're now using that someone could put into coffee. And I actually put one of those sticks into the tea, and then I got to thinking about ratios and whether or not ratios are important. Like I know, for example, for 5-HTP and tryptophan, the recommended ratio is about a 1:10 ratio for people who are dealing with depression and things like that. I'm curious about when you're creating a nootropic compound, do you look at ratios and how do you figure out what ratios are effective?

Dr. Hill: Yeah. I mean nootropics are still a bit of a Wild West. truBrain and of course me and a team of neuroscientists took a very rational approach to building the truBrain blend. And we did so by looking at, or by electing compounds that only had decades of safety and efficacy. None of these research chemicals that have just been released, or nothing that has not been used extensively in humans. And because of that, we had decades of a paper to look at where different doses were examined in individuals. Now that doesn't actually account for the combination of ingredients. And so I actually started working on a nootropic formulation well before I was involved with truBrain, just sort of personally self-hacking, if you will, and this is sort of part and parcel of the nootropic space over the past decade. It's an awful lot of self-hacking, trying different compounds, trying different ingredients, herbs, amino acid, supplements. And I did a lot of that. In my grad program, I was looking for some cognitive support, I tried, got some psychostimulants which I had been prescribed a decade before with some success, but I tried them as a slightly older dude with an older liver and I could not tolerate psychostimulants. I got high blood pressure issues and things from them. So I had to find another solution.

I was teaching classes, and doing research, and trying to finish my dissertation, really stressed out, really overwhelmed, and eventually got into nootropics. And I had taken courses in psychopharmacology and pharmacodynamics, and it was very difficult for me to figure out what was safe, what could be effective, what might be useful. And so after a couple of years of self-experimenting, I started you know trying my friends on to this blend of compounds that I had been working on, my mom, other folks in my family started trying it, and then after a couple of years of writing down a lists of candidate nootropics for people that they then wouldn't be able to find because it takes a little bit of sleuthing to sometimes get some of these things on the internet, and they also wouldn't feel safe about where they're coming from necessarily, I met Chris Thompson of truBrain and we decided to formulize you know what I thought was a best-in-class nootropic sort of starting place for people. And that was the start of truBrain two and half years ago. So it's not so much that we know what all the interactions of the different compounds in truBrain are, it's that we've established they're safe and effective. And subjectively, myself and a lot of other people involved with the project, have figured out, if you will, what a good ratio. And there's some bro-science here, there's some conventional wisdom, if you will, not that there is such a thing.

Ben: Yeah. ‘Cause sometimes you're taking things that have been shown in isolation, in a single study to be efficacious and then combining that with one of the things when a study hasn't actually been done, but you just kind of keep your fingers crossed that all those components…

Dr. Hill: It's informed, if you will, guesstimation. So one example is, there's an early study, maybe 20, 30 years ago by one of the early truBrain advisory board scientists named Christoph Michel that looked at the dosing of piracetam, and piracetam is the sort of poster child for nootropics, it's in the true brain capsule format. And piracetam in this research paper was looked at in three different doses: 2.4, 4.8, and 9.6 grams and Christoph Michel showed that the micro states, the complexity of the EEG goes up the most at 4.8 grams with a single dose. And from that, you find there's now a big broscience or conventional wisdom in the nootropics world of people saying 4.8 grams of piracetam is the necessary dose. Except what people sort of fail to realize is that was an acute dosing study, not a chronic dosing study. And the racetams seem to have a reverse tolerance. They were better the longer you take them. And so when I was deciding initially where to peg the dosing for truBrain, I wasn't looking at, “Oh! The research says 4.8 milligrams is the highest amount of brain change.” I thought about what it would mean over time and realized that 4.8 grams every single day would probably be too much. It would be a larger dose than an acute dose once. And so it's logic like that that led me to end up putting about 3 grams, if you will, of piracetam in truBrain.

And it was sort of a process. It took a lot of intellectual wrangling between the neuroscience team. I am the lead of the neuroscience team at truBrain, but we have a couple other neuroscientists, a couple food tech people, a pretty deep science team. And we sit down and bring up studies, and hash things out, and argue about what might be true, and it's applied science, and science is never definitive until it's way late in the process. And we're trying to make the most honest and best approximation with the most safe compounds we can, and then we're also totally transparent. That's one thing that truBrain does differently. We tell you exactly the ingredients, the exact amount of every ingredient in the truBrain blend.

Ben: Yeah. And I wanted to ask you about just a few of the ingredients real quick because I'm not familiar with some of them. I'm familiar with aniracetam and piracetam, but it looks like you guys use oxiracetam. How's that different than the other two?

Dr. Hill: So we use piracetam and oxiracetam as the two racetams. Now a racetam class of compounds is a sort of starting place for nootropics. Racetams, and piracetam being the first one, were synthesized from the neurotransmitter GABA, and it looks like the piracetam binds to glutamate receptors and increases alertness that way. We still don't know all of the effects, but all of the other racetams were eventually synthesized from piracetam and have similar but slightly different effects based on either other organic chemistry rings that are added to them or changes in fat versus water solubility. And so I can describe some of the subjective differences. Aniracetam, which you are familiar with, is often very anxiolytic, it's very calming. And it's a really big nootropic in Japan for that reason. People really love it because it's a calm focus. Personally, I don't love aniracetam. It makes me kind of lethargic and depressed, and I've heard that from enough other people that I decided not to push it into truBrain. Piracetam has the most broad, sort of subtle range of effects, and then oxiracetam is very much like piracetam except it's a tiny bit more stimulating and occasionally we get people saying things like it improves their sensory experience a little bit more, like they're appreciating colors, or music, or sound a little more. And piracetam, we get a few more reports of verbal fluency, access to words. And so they seem very similar, but there seems to be a little bit more verbal effect for piracetam and a bit more of a sensory effect from oxiracetam. In house, we've been experimenting with combining them, and the newest version of the drinks, the think drinks that truBrain is coming out with, should actually have both oxiracetam and piracetam in them, as well as all the other supporting compounds to make the racetams work well.

Ben: Got it. Okay. So in addition to oxiracetam, another couple I wanted to ask you about is uridine. Uridine. What does that do exactly?

Dr. Hill: It's cholinergic. So in general, the strategy for doing nootropics should be, at least the starting place, a racetam and a form of choline, and uridine seems to have some of the same cell membrane upregulation effects of a cholinergic compound, and affect hopefully, ultimately choline synthesis in acetylcholine, which is the neurotransmitter involved with memory and attention. And so uridine's actually only in the boost versions of truBrain. We ship this as a regimen where you take it, the capsules morning and midday, and then we have 20 days worth for your workdays, and then there's four boosts in the capsule box. And the boosts are, in the capsules, oxiracetam, centrophenoxine, and uridine. And it's a much different sort of formulation, a little more stimulating, uridine also seems to affect protein synthesis in a way that other things may not. And so it's a little bit more of a boost, a little more of a subjective feeling, if you will. But it's not one of the main compounds. We don't put it in the day to day blend, so to speak.

Ben: Okay. Gotcha. And then last one I wanted to ask you about, one that I'm also unfamiliar with is centrophenoxine.

Dr. Hill: Again, that's also just in the boost, centrophenoxine. And centrophenoxine is cholinergic. It's DMAA and something else. It sort of has a very similar a back that a choline has. It's sort of a substitution compound for a choline source.

Ben: And for something to be cholinergic, all you're talking about is it's increasing the rate of neural firing in the brain? Is that what it's doing?

Dr. Hill: Cholinergic meaning it's increasing the metabolism, the activity, or something around acetylcholine. And cell membranes are also made up of choline compounds. Phosphatidylcholine, for instance. And so when you take choline in your mouth, the brain or the body will turn it into cell membranes and actually make it into phosphatidylcholine. We have a cholinergic compound in truBrain called citicholine, or CDP-choline. And citicholine seems to actually act as an intermediary in the uptake of choline into cells and in the synthesis of the cell choline, phosphatidylcholine. So that's sort of making cells healthier, and then choline itself is the raw material, if you will, to manufacture the neurotransmitter acetylcholine, which is the memory and attention, or learning, if you will, neurotransmitter.

Ben: Okay. Got it. Interesting. And so you can take this stuff in like a liquid shot or in a capsule, and there's a few different blends depending on whether you want like the boost to add on to the initial shot, or whether you just want to stick with the initial shot.

Dr. Hill: And the liquid drinks, the think drinks have, two out of three of the flavors have caffeine in them as well, 80 milligrams of caffeine. And the capsules have no caffeine 'cause we didn't want to initially, a lot of the energy drink and brain performance supplements out there rely on sugar and caffeine for the subjective effects. We didn't want to do that 'cause the capsules, which were the first two years of our products, have no caffeine and will remain caffeine free. While the drinks, because people expect to have caffeine in the drink, two out of three of the drinks have 80 milligrams, which is not a huge amount of caffeine.

Ben: And for the drinks, do you dissolve those in your mouth? Will you get better effect if you absorb them in your mouth and hold them for 60 or 90 seconds like some of these essential oils and tinctures? Or do you just swallow?

Dr. Hill: We just swallow them. It's a one ounce, or one and a half ounce little pouch of liquid. Some folks just tear up the top and squirt it back. Other folks put it in like sparkling water, mix it with their smoothie. It's already a liquid and everything's already dissolved, and therefore the absorption of the drink is dramatically increased compared to the capsule absorption. So for similar ingredients in both, we actually are able to put much less of them in the drink and still get as much, if not more, of an effect because liquids are absorbed, I mean I think if you take the same, this is general chemistry and metabolism, the same compound as a powder versus a fully dissolved liquid ends up with like 30% absorption as a powder and 95% absorption as a liquid or something. It's dramatically different. And so yes, you do get more of an effect from the liquid, but I think you need to go sublingual. The liquids hit you very quickly, you feel them within 20 minutes, so I think we're already getting a very quick absorption, even simply swallowing it and not having to hold it in your mouth.

Ben: Okay. Gotcha. Now I know, those of you listening in, we've covered a lot of stuff today. I'll put the links over at bengreenfieldfitness.com/weedbrain. That's bengreenfieldfitness.com/weedbrain. But I've got one other the thing to mention, and that is if you go over to those show notes and you leave a comment, what we're going to do is actually have, well first of all, a couple things. Anybody who wants to get truBrain, not just one person but anybody, if you go to truBrain.com, that's TRUBrain.com and you use code Ben, then you'll get 50% off of any drink or capsule, or they even have like these coffee kits with the little smart drug packets that you add to coffee as well. But you just use the coupon code Ben over at truBrain.com. That'll get you 50% off the stuff that Dr. Hill helped to formulate, this truBrain stuff that we're talking about.

And then also, if you have a question or comment about THC, CBD, smart drugs, nootropics, your own comment to add, et cetera, what I'm going to do is for the most compelling, engaging comment that gets left on this particular podcast over at bengreenfieldfitness.com/weedbrain, I'll get you a box of 15 of these truBrain drinks just shipped straight to you. I'll contact you privately if I like your comment. So that's a box of 15 of these truBrain drinks that you can get sent to you. I'll get them, I'll send them over to you, and that is if you leave the most compelling, engaging comment over at bengreenfieldfitness.com/weedbrain. So I know you've got to run, Dr. Hill. This has been really interesting. It's always nice to get the educated opinion of a scientist, a nerd.

Dr. Hill: (laughs) [1:02:05] ______ that's right. I'm glad I could add a little of science today.

Ben: Yeah. Cool. I'll get your address later, I'll get you a bottle of that CBD to try if you want try the water soluble stuff as well.

Dr. Hill: Yeah. That'd be great.

Ben: So anyways though, folks, thanks for listening in. Again, the show notes are at bengreenfieldfitness.com/weedbrain. And until next time, I'm Ben Greenfield along with Dr. Andrew Hill from bengreenfieldfitness.com signing out. Have a healthy week.

A few weeks ago, I talked on this podcast episode about whether THC can cause damage to the grey matter in your brain.

But, frankly, I spent very little time addressing the matter on that particular show, so in today's episode, I'm revisiting the topic of THC, brain damage, liver damage, myths about marijuana, CBD, smart drugs, nootropics and more with Dr. Andrew Hill, Lead Neuroscientist at truBrain, and one smart cookie.

During our discussion, you'll discover:

-Why left-handed people are more sensitive to chemical stimulants…

-The truth behind the evidence that THC can shrink the brain…

-The important differences between THC and CBD…

-How Dr. Hill can “reset” tolerance to marijuana using neurofeedback in his clinic…

-If there is a deleterious effect of THC on the liver or other organs…

-How to map your brain and change your brain using neurofeedback…

-Little known smart drug ingredients such as oxiracetam and centrophenoxine…

-And much more, including a killer giveaway at the end of the show!

Resources & studies cited in this episode:

Decreased grey matter but increased connectivity (not controlled for SES):

http://www.ncbi.nlm.nih.gov/pubmed/25385625