Todd Becker is a biochemical engineer and works in biotech in Silicon Valley. He has a masters at Stanford and degrees in biochemistry, chemical engineering, and philosophy.
Todd Becker’s philosophy and biochemistry background is the perfect combo to help us figure out how to combat life stressors, ultimately making us more resilient and able to live happier lives. In this interview we cover:
Using hormesis to cure myopia, rid ourselves of phobias, combat drug addiction, grow new dopamine receptors, and improve libido, all by implementing protocols like cold therapy, eating a low carb diet, exercising, and practicing intermittent fasting and modern Buddhist thinking/hormesis CBT.
Improving or Curing Myopia
Q: What issues did you deal with and what improvements did you get?
A: No severe issues, just a couple of challenges. He used to have glasses for myopia but got rid of glasses and improved eyesight. Wanted to lose weight so went on a low carb diet and lost 10-15 lbs. Then he improved ways to do this further with intermittent fasting and dropped 25-30 lbs effortlessly. Being a parent of teenagers is stressful, so he used philosophical principles to become more resilient. The common connection with all of these practices is a principle called hormesis, it’s a way to embrace stress in order to avoid it. I found that this principle is broadly applicable in many different areas- if you look at immune mechanisms, metabolic, etc. We have evolved to handle stress by exposure.
Q: What number were you before and after myopia?
A: Mild. 1.5-2 diopters. Enough to need glasses for driving. He doesn’t need glasses anymore. His eyesight is at least 20/20, maybe better. This practice has helped people even with severe myopia (at 6 or 7), reduce or eliminate it completely.
Q: A ton of people have myopia (nearsightedness), including me. I looked at your protocol and tried it, but since I’m at 5 it’s hard. You have to wear your glasses a lot of the time so you’re kind of reversing the benefits that you made. I got a headache with the plus lenses. I’m assuming I did it wrong and you would do it more gradually.
A: Sounds like you did it wrong. When you go to optometrist you’re given a short-term solution/instant gratification to see right away with a corrective lens, but this doesn’t get to root cause. Myopia is caused by elongation of the eye to where you can no longer focus the image on the retina; it’s focusing on the image in front of the retina. By wearing corrective lenses you’re providing a crutch and making the problem worse. There’s something called the incremental retinal-defocus theory of myopia, and there’s a lot of evidence for it in animals. What happens is when the image focuses a little either in front or in back of the retina it stimulates differential growth of tissue. So if you’re always looking close up your eye is going to try to adjust to accommodate that, and if you’re wearing minus glasses for distance, it makes your eyes feel like they are looking close up. In this way, you aren’t forcing your eyes to work and to see from far away.By reversing that process and making your eye focus incrementally further away, you’re going to stimulate the neuromodulators and eventually the eye will reshape itself.
Q: How long did it take you to correct your myopia?
A: 1 year
(ME): It could take me even longer, like 3 years
A: So you’re at a 5, take a meter and divide it by that, so you can see a fifth of a meter, which is uncomfortable. You only need the plus lenses when you get to 2 or less, because at 2 you’re reading at 19 or 20 inches away, so you can read comfortably. Then get plus lenses to make your eyes better. Shave half a diopter when your eyes have stronger myopia. Find a lens that allows you to read right at the edge of comfort provide incremental stress-only doing it for a few hours a day. For driving, shave half diopter so that you can still see, but your eyes will be working harder. One general principle offer hormesis-goldilocks principle is not too strong, not too weak.
For reading purposes, get a lens where if you lean back a bit, your vision is a little out of focus.
So, if you have mild myopia you would need plus lenses, but if you have strong myopia you don’t need any lenses, just read right at the boundary. If it gets tiring, bring it in. You can find lenses at alders.com that allow you to dial your lens in as you train your eyes. You shouldn’t even really notice these changes until your eyes are all of a sudden better.
Q: What about glasses for astigmatism?
A: As you work your way out of myopia it tends to reduce astigmatism as well. There are also eye exercises you can do to try to work your way out of astigmatism.
(ME): I got glasses without correcting astigmatism and actually like it better. If I like it better do you think it’s probably good for me?
A: I think so.
Q: What other forms of hormesis do you use and what effects do you notice?
A: Intermittent fasting is one of the most powerful. You can do it one of two ways; one way is to eat within a 5-hour window. I tend to prefer dinner, so when I do IF I’ll skip breakfast and lunch and eat an early dinner. The point is if you go without eating for at least 12 hours, ideally at least 14-16 hours at a stretch (includes sleeping), you start to lower your basal insulin level, and start to back off on motor activation, and turn on autophagy which is an intracellular cleaning process (has a lot of benefits in terms in terms of removing damaged proteins). Your BDNF (brain-derived neurotrophic factor) gets a boost, a lot of benefits for the brain, metabolically and hormonally you get a lot of benefits from this. You can also do alternate day fasting, where you don’t eat for a day, then eat a lot the next day-not as convenient. Do IF a couple of times a week. Good for energy as well. If you’re used to eating six snacks throughout the day, then when you suddenly fast you may experience hypoglycemia and blood crash; this is not advised. Go gradually. Cut out snacks, so you are eating a solid three meals, then try to eat breakfast later before finally skipping it. Can also cheat a little by eating high-fat snacks (low protein and carb) that will still allow insulin level to go lower, and will train you to up-regulate your lipase to activate fat stores. Eventually, you get to the point where you have constant, even energy.
(ME): I think IF is great, but it happens to be I deal with people who have a certain set of issues. If you’re overweight, with standard American diseases and no serious health issues, then I’m completely on board with you there. And you said you have to do it at a level where people can tolerate it, but I want them to be a little careful; this is because a lot of people that I deal with are too thin, and have lower insulin, and also get hypoglycemic. Their cortisol level isn’t working right to respond to the hypoglycemia. But if you are robust enough at that stage, you maybe want to push the envelope.
My insulin is 2 without any fasting. There are different changes in biology. At some point when my health issues were worse I needed to eat every few hours otherwise I would get hypoglycemic. If you feel you are getting hypoglycemic you’re going overboard, but if you’re healthy enough, gaining weight, and have high insulin, I would recommend IF. Another problem with this relates to the circadian rhythm. I’m very into eating within a 12-14 hour period; if I go 16 hours it’s too much for me. Also, if I don’t eat enough calories in the daytime (note that I don’t have an issue with getting fat), I’ll get hypoglycemic at night. If I have last meal at 5 and wake up at 8 I get hypoglycemic in the night, triggering stress response before I go to sleep. I feel wired, and I don’t want to eat when I go to sleep.
Working on a post with the big 4 hormones that help determine if you are struggling to lose weight, or struggling to gain it. One problem is if someone’s mitochondria aren’t working right, then they’re not producing enough ATP. If you’re not producing enough ATP then you won’t produce enough insulin. When you have chronically low levels of insulin, that causes changes in the hypothalamus (this is theoretical but based on science-animal studies, etc.). Changes in the hypothalamus are going to activate a stress response to counteract low glucose only when it’s lower; thus the threshold becomes lower. So instead of activating a normal stress response when glucose is 80 for instance, it’s going to go to 60. But the problem is that you’ll get hypoglycemic. When you get hypoglycemic it causes an excess of glutamate and that breaks down your mitochondria. I feel really weak, then I have a burst of energy from excess glutamate, then tired. In the beginning, I needed to eat every 2 hours, but now I feel better when I wait 12 hours.
A: You’re describing a control system that’s not well balanced. The fact you’re going so long before the hypothalamus kicks in means there’s something wrong with the control system. The underlying issue may be inflammation or something like that.
(ME): I agree. What triggers it is eating foods I’m sensitive to. I think it’s localized inflammation in the hypothalamus, or could by systemic inflammation. Orexin system (wakefulness neurotransmitter) isn’t working well, and circadian rhythm isn’t working well. At a certain time, certain metabolic systems are supposed to work better but in my case, it was as if, in the morning, my body was in metabolic processes that should be happening when I’m sleeping. It could also be from oxidative stress. There are definitely changes where the people I deal with are getting hypoglycemic way more often, and having hypothalamic issues where the central processor isn’t working well. I agree if you’re overweight and don’t have these issues, which is most of the population, they should follow your approach; but for some of my readers, they definitely have to pay attention to what feels right.
A: He agrees, if the control system is out of balance then there are other issues. It’s really important not to go overboard and submit yourself to excess amounts of stress, whether physical, mental, etc. A common question is how do you know what is the right amount of stress. At different times in your life, you can tolerate different levels of stress. Heart rate variability (HRV) is a great tool for this-not heart rate, but the degree for which your normal heart rate varies. Instead of it being once per second (which is no variability), it might be 1.05, .95, 1.15, .85 seconds. The more variations you have in heart rate, the higher the HRV. You might think this is a bad thing because of arrhythmias for example, but it turns out all the rhythms in our body, not just the heart, but the brain, gait, how regular your step is, reflects something about your physiology. It turns out there’s a balance between the sympathetic and parasympathetic system. If you’re too wired and high strung (waking up at the wrong time in the night, sympathetic may be in overdrive, similarly when you overtrain), then your HRV tends to go down, and become more regular, which is not a good thing. On the other hand, when you’re relaxed, fit, well-rested, your parasympathetic nervous system is in control, and you get more HRV. So the way athletes use it (and you can buy apps), is by tracking HRV to see if it is at a good level or increasing. When they start to overtrain, they will see a significant dip in HRV. They will see this before starting to subjectively see other symptoms. Then they can back off on training. The same thing can apply to stresses in life; if you’re working too hard and see HRV go down, you know you need to back off. In the other hand if you’re doing nothing and your sympathetic system is under active, you can also see imbalances. There are different measures of this. It’s a great way to do experiments on yourself. I learned a couple of things that weren’t out in the literature about things that benefitted and hurt. I was surprised about alcohol. I had no real effect with one drink, but even 2, or especially three drinks, HRV would crater.
Q: So the main determinant of HRV based on your explanation is how much the parasympathetic nervous system is activated – is there any other basic determinism of HRV?
A: It’s the balance of the parasympathetic and sympathetic. A little oversimplified. There’re multiple different measures where you can measure things on the frequency and time domain; the simplest answer is yes.
Q: So alcohol is something that will activate the sympathetic nervous system very potently.
A: It surprised me because alcohol is making you more relaxed, but it’s oversimplified to say the sympathetic nervous system is about relaxation.
Parasympathetic Nervous System
Q: I think it’s because it’s increasing GABA, but it’s increasing your stress response. So what is the parasympathetic nervous system, is that the vagus nerve? What else is involved? The sympathetic system, in my mind, is the hypothalamus producing the stress response and cortisol, CRH. The parasympathetic would be something like the vagus nerve transmitting signals, probably getting those signals from the brain, going to the vagus nerve to a whole bunch of different organs. Is that what the parasympathetic nervous system is?
A: The vagus nerve is one of the transmitter effects. It’s not one thing, it’s a whole network throughout the whole body: your gut, brain, the connection between that, a distributed system. The hypothalamus does play a role.
Q: What is telling the heart to beat at different frequencies. The vagus nerve connects to the heart. Is there something happening in the vagus nerve that tells the heart.
I’m trying to get a big picture of the parasympathetic nervous system, the whole system, instead of just rest and digest. Knowing the basic biology if it will allow me to better guess about if things will increase the stress response, and be negative for the HRV, or increase the vagal tone, as a benefit to HRV.
A: It’s the balance between the two systems. The vagus nerve does have a big impact on heart rate. It’s beyond when I can remember specific hormonal cascades, but I can find some references.
Q: Me too. For now, I guess the main thing that I know is the vagus nerve connects to the heart, and there are different things that influence this tone. The vagus nerve works with acetylcholine potently so there’s probably something like that going on. And the vagal tone is fuzzy, what exactly is it. Maybe just how it activates the vagal nerve, increasing vagal tone. Or how sensitive the vagal nerve is. For example, if you take in capsaicin (cayenne and chili) it will desensitize it in certain ways. I need to look into this.
A: It’s good, I like to delve into the mechanisms too, but I’m not sure about this. One thing that made my HRV go up and quickly, 10 or 15 points, and consistent, and could reverse alcohol effect with this is cold showers.
(ME): What I just thought of.. the reason why it’s important to know exactly what influences the parasympathetic: cold showers increase the thyroid releasing hormone (TRH), TRH stimulates the vagus nerve, which will increase HRV. Even though it might increase stress response in the beginning, it increases the parasympathetic nervous system at the same time.
A: Yea, it goes against my intuition, because it can be shocking-heart beating rapidly, etc. until you adapt to it. So you think it’s related to sympathetic system, and it probably is briefly, but you’re turning on thermogenesis, you’re turning on acetylcholine, and activating a lot of responses. We’re always governed by homeostasis, so whatever stimulus we’re exposed to, the body is trying to take that stimulus and bring us back to the middle again. So he thinks that with thermogenesis your body is trying to calm you down. That effect lasts hours after the fact. The more you do it and the more you adapt to it, the greater it is. The sort of fear and anxiety gets less and less after 1-2 weeks. One of the psychological benefits of cold showers is that it completely dampened the anxiety, fear, anger response to adverse events. When someone cuts you off in traffic, for example, you don’t react as much. Also has some of an antidepressant effect. I don’t fully understand the mechanism
(ME): I’ll take a stab. So it’s working through the vagus nerve and the parasympathetic, so you’re more relaxed. I would also say TRH is also an antidepressant hormone, so when you release that it’s stimulating the vagus nerve, but it’s also an antidepressant hormone. I’ve taken TRH by itself (expensive). You probably get a bigger effect when it’s released naturally, but I do notice some of the same effects. It’s calming, anti-stress. But it’s hard to absorb. You have to take it sublingually. I think the cold showers are also probably producing endorphins.
A: There’s some interesting psychological research on this. One paper is by Richard Solomon, the appointed process theory of emotion. He studied 2 interesting things:
Why is it that skydivers, when they jump out of a plane, the first time they are terrified. But the more they do it, that fear effect goes away. And why is it at the same time that they have this euphoric effect that last throughout the whole day, just from that brief jump, which gets more pronounced with time. He explained it as the homeostatic effect of trying on certain inhibitory processes. You have this fear, and psychologically there are processes that go on that want you to inhibit the effect.
The other thing he looked at was addiction. It had the opposite effect. Here you have immediate gratification, but then you have a tolerance effect, needing more to achieve a high. You become increasingly depressed and anxious.
You can look at hormones and neurotransmitters-the biochemistry is different in each case. You either have the thrill of an activity and a period of discomfort, followed by increasing euphoria. Or you have the reverse, which is the addiction of the brief pleasure followed by increasing negative effects and withdrawal. It’s an interesting general psychological principle.
A: People trash cortisol but it’s a useful hormone in its natural state. You want to have it high in the morning, and you want it to go down in the evening. The problem is when it’s always sustained at a high level, that’s when you get into the chronic issues.
Q: What other things did you find affect HRV: cold, alcohol.
A: Intermittent fasting, or when I do a low-carb or ketogenic diet (ketogenic may increase it even more than just the low carb). Moderate exercise can keep HRV up, but if I exercise intensely, HRV plummets, but the next day or two it comes back higher than where it was. So certain effects are immediate, like alcohol or cold showers. Some other effects, where you are willing to take a periodic drop in HRV, eventually puts you in a higher place. I think you have to track it for a period of time that works for you. It’s a very individual response.
(ME): I bet breathing exercises have an effect.
(ME): The reason why I’m talking about HRV so much is that there are a lot of studies showing that high HRV is correlated with good health status, and lower HRV is associated with a bunch of disease states. Figuring out causation and getting it up is very important.
A: Yes, and there are a lot of clinicians that use it as a leading indicator for infections and cancer, and the drop in HRV shows up before certain other clinical systems.
Me: I want to start measuring HRV, but none of the measurers got good ratings on Amazon. I’ll have to find a good one.
Hormesis, Fear, Happiness
Q: How do you use hormesis to conquer fear?
A: Fear is a stress. Applying hormesis involves finding a stress and exposing yourself to it so you become more resilient to it. The classic example is lifting weights. When you lift weights you’re damaging your muscle fibers. When they heal they come back stronger. The same thing is true psychologically-exposing yourself to stresses in the right amount can build resilience to it. Exposure therapy-you expose yourself to the object of fear in increasing dosages. Used particularly effectively for fears like fear of snakes. At first, the person is terrified. They look at pictures, then see one in person, and eventually get to the point of touching or handling it. It’s a way to decondition yourself to fears. Public speaking is another fear conquered by exposure by just doing it.
Q: Have you overcome any of your fears, are you afraid of anything now?
A: I don’t really have any fears, but where he’s experienced this directly was with rock climbing. Used to have acrophobia. The more he’s done it, he’s almost completely reconditioned himself. You still have to be safe, but you can definitely condition yourself to fear of heights.
(ME): I’ve used hormesis in some ways to overcome my fears, over a long period of time without realizing it. If you just expose yourself to something, you stop being afraid. One of the things I used to be afraid of, like most guys, is approaching random people, especially women. It’s the most dreaded thing for guys. Tim Ferris spoke about it. Out of everything he was doing, that was the most dreaded thing he was afraid of. Also, Larry David mentioned it in 60 minutes. It’s a common fear among men. At a certain point, I was approaching a bunch of random women and got over it. A lot of times it’s being afraid to fail. I think fear comes down to the ego. When you expose yourself it brings your ego down, and you become more resilient. Now I’m generally not afraid of anything, starting new ventures, etc. I think society is afraid of failing at anything.
A: One of the key fears is rejection, rejection therapy. Every day you have to be rejected at least once. Whether it’s asking a girl out or asking a ridiculous thing of a random stranger. Find something that someone will say no to. And it immunizes yourself.
(ME): I do it all the time, with outrageous things. You do it enough it goes away.
A: If you take it further step forward, you can turn it into a philosophy. One of the appealing philosophies is stoicism. The basic idea-stoicism isn’t about being emotionless and not responding to anything, rather it’s a way to inject joy and happiness into your life. William B Irvine, “A Guide to the Good Life-The Ancient Life of Stoic Joy.” He talks a lot of the ancient Greek and roman stoics-Epictetus, and Mark Cornelius, and translates some of their learnings to the modern world. He gives examples of how you can use contemplation to negative things, building a deeper inner reservoir for joy and happiness.
The essence of stoicism is exposing yourself to things that can embarrass you, or participate in things like living minimally, or voluntary poverty. Some of the Stoics were pretty wealthy like Seneca, he would go off for a week or month and would live in a very spare environment in the countryside with minimal food, fasting, almost in poverty. It greatly enhanced his appreciation when he came back. Negative thinking, almost like a substitute for prayer. You think about all the things you value: your friendships, your stuff, your job, and you progressively go through and think about losing all of those things and put yourself in that situation. Then you appreciate having everything. Putting things into perspective. Used to get upset when got a parking ticket, but then looks at it more like..50 things, at least, will happen badly in the year. It’s just a part of life. None of them are that consequential. What’s really consequential are your values-random events in life shouldn’t really bother you. Stoicism is training yourself, how to think about events in the world. As a result, you’re less attached and happier. It’s almost kind of the western analog to Buddhism. But I think stoicism is a western tradition-tied up with greek and Roman philosophy. Aristotle, Plato, there’s a whole line of thinking that mirrors some of the eastern thinking. I think stoicism is more analytical about it. Some of the same ideas occur in Buddhism but described in a different language.
Q: We’re getting into hormesis in thinking. I’ve been practicing this for a long time, and I’ve also adopted various Zen philosophies. In America, we’re into positive thinking, and I just think of everything negatively-what if everything just fails, house burns down.. for a second you could feel bad, but I’m much more resilient and more detached.
A: CBT is like a modern version of stoicism.
(ME): It can be misleading saying training yourself. It’s more of just exposing yourself, not taking situations too seriously, having a perspective, and thinking of worst case scenarios (not dwelling on them), but that’s ‘training’ yourself.
A: Key in the training is the gradualness of it. Biological studies on it-researchers like Calabrese study plants and animals and bacteria, exposing them to different levels of toxins, dietary stress, UV, finding in every case there’s this u-shape curve, where there’s an optimum level which stimulates the positive response, the adaptor response. But if you go too high, you get a negative response. That’s the art of hormesis-finding that zone for you, and continually pushing it a little bit, but not too much.
Q: Have you ever looked at sun exposure and HRV?
A: I haven’t. I’m a big believer in getting good sun exposure, discounting a lot of the fear of cancer. I think the big issue is for people who are indoors all the time. Summer comes and they lay out all day in the sun. Increasing sun exposure gradually is important. There are some cancer benefit effects. The D that you get is a different form than what you take orally-sulfated, and calcitriol instead of calcidiol.
Q: Is there any process by which sun stimulates calcitriol (activated D) more than the vitamin D3 in the blood?
A: Vitamin D3 that you’re measuring, calcidiol, is an intermediate. There’s some interesting feedback, in some circumstances as a precursor it will lead to higher levels of calcitriol, but it can also interact with vitamin D receptor and even inhibit at high levels-tricky regulatory mechanism. Just supplementing with high levels of Vitamin D3 doesn’t necessarily result in high levels of the biologically activated form. Also, the kind that you measure, calcidiol, is not always reflective of the calcitriol.
Q: So that’s why I was wondering if you’re getting sun if that increases calcitriol more than if you were just taking D3. Do you know?
A: I don’t know specific research, but have read that. Also, there’s the difference between sulfate and non-sulfated forms.
(ME): You’re also getting a load of infrared from the sun. UV is also suppressing the overactive immune system in some ways. Maybe photons and the spectrum of light. You’re getting a whole bunch of benefits from the sun that you aren’t getting from D3. And I’m definitely on board if you have too much of the inactive form – it can compete with the vitamin D receptor. Do you know what level that is, or is it dose-dependent?
A: Believes it varies by individual. Same with any metabolite-calcium, or cytokines. If you raise the level of one unit, it can deplete another. It might be true that certain people with health issues have low calcidiol levels, but is that cause or consequence. If it’s consequence, adding more in the system isn’t going to necessarily correct the problem.
Q: Most of the good clinical trials don’t come back as being positive for vitamin D3 supplements. Unless you’re really deficient. Beyond 30 ng/ml the studies don’t show significant benefits. It’s more because you need the calcitriol, the active form in the body, that really binds to the vitamin D receptor.
A: Answer isn’t to sometimes take supplements like calcium for bone density, which might put calcium in the wrong place, but to exercise.
Q: And take K2 which you will disagree with…
A: Well, may help. When he took vitamin D3, he didn’t notice much benefit (but doesn’t have significant health issues), and he has high bone density, so went off it again. Don’t get colds and infections.
Q: I think if you took some it wouldn’t hurt you. I don’t take it either really because I get sun.
A: I think eating whole foods, getting good sleep, having good patterns, exposing yourself to natural stressors-cold, exercise, social stressors, these are the things that activate systems in your body in terms of immune health. If you grow up on a farm, or around animals and nature, you’re going to activate T cell response and have less tendency to pick up autoimmune disorders. The answer is exposure. If you use your eyes and look at things outdoors at different distances, they will go through a full range of motion. Use natural endogenous capabilities for health.
Q: I agree. Did you ever test how much calcium you were getting from food? RDA, or don’t care about it?
A: I eat a diet in natural meats, greens, leafy vegetables, little dairy, fish. The other thing is I don’t have absorption issues. If I had absorption issues maybe I would need to supplement. If you’re in good health you let your body naturally select what it needs in that diet.
Q: What about implementing hormesis with libido and sleep?
A: Good regular physical exercise is a big key to good sleep; when physically tired you sleep better than mentally tired. Overeating can mess up sleep. But maybe when in hypoglycemic state one maybe needs to be careful to eat regularly. With libido, there’s an argument for moderation. If you allow time between sexual events, you tend to build up sexual libido. But to some extent, it’s dependent on how old you are and level of health. There are interesting comments I get from men who are dealing with pornography addiction, particularly from a young age. Then they are always going after stronger stimuli and then they have trouble in real-world sexual encounters because the reality is not as stimulating as what they’ve seen on the internet. There’re good people blogging on this site called reuniting. There’s a theory of rebooting the theory is to abstain for a period of time, cut out pornography and the typical response is a period of almost depression and loss of interest. After a month or two, their libido comes back really strong. They are becoming more in tune with natural sexual stimuli. Some people take it as an anti-pornography concept, maybe some people can handle it, but for people who have become really addicted and their libido has been shot by it, the rebooting period has been shown to be effective-you can say it’s a hormetic response.
Depression, obesity, etc. have to do with receptors. We have receptors in the brain for dopamine, which respond to novel stimuli and pleasure. If we’re constantly indulging in really tasty food, lots of sex, particularly drug addictions, you’re maxing out stimulation of those dopamine receptors. You often get a down-regulation response. Over stimulus and down-regulation, you’re going to be somewhat desensitized, and when the stimulus isn’t there, you’re going to be somewhat lacking pleasure. It takes time to grow back dopamine receptors. Cold showers and intense exercise help with drug addiction, libido problems, etc. and you are able to upregulate dopamine receptors. Brain imaging activation of dopamine and serotonin reception in the brain. Really boils down to receptors.