The Brain Stage: The Power & Promise of The Cephalic Phase for Health

Neuron in the brain on blue background. Neurons are key to The Brain Stage.

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[00:00:03] Hi I’m Dr. Alan Greene pediatrician and I’d like to talk with you tonight about The Brain Stage.

[00:00:10] I remember vividly when I was a pediatric resident in training go to a Grand Rounds about a surprising topic.

[00:00:18] The function of the brain and the function of the skin and one of the things that dermatologists talked about was a common procedure freezing warts. Freezing warts was then, and is still, one of the most common ways to get rid of warts. What she talked about was how wildly different the results were in different studies. People use the same tools the same techniques and got wildly different results. Why? Well, one included that freezing doesn’t kill the wart virus — doesn’t eliminate it. Instead what it does is create a signal that then later triggers the immune system to knock out the wart, but different in different settings. Another thing she talked about was the fastest pain relief for a child who skins their knee is a smile or a kiss from mom.

[00:01:15] And that was sweet and not terribly surprising. But what was surprising to me was that the wound also heals faster. How could it be that the complex machinery of wound healing is changed just by the attention of the mom?

[00:01:38] Another question. Suppose you have a red pill and a blue pill that are made of exactly the same medicine and exactly the same dose in the same manufacturer.

[00:01:49] You might expect that they would work the same in studies but you’d be wrong.

[00:01:57] Just because of their appearance the two pills consistently work differently. So I want to share with you just two things that will explain all of that and give you a fresh window into how our body works.

[00:02:11] Number one every pill has a hidden brain stage. Every pill has a hidden brain stage. So why does the brain stage? The best way to think about that is to compare it to something where we’ve got a lot of science. Something that you may not have heard of called the cephalic phase of digestion. Now it’s not a phallic phase, that’s cephalic phase. That just means having to do with the head. Digestion is an incredible process where we take food from the environment, goes into our body intricately is assimilated into us through a very complicated process. But what you may not know is that digestion begins before the food ever makes it into the mouth.

[00:02:57] Here’s how it works. You spy a delicious slice of key lime pie and when you see it the light waves are hitting the pie. They reflect off of that. They’re focused by the lens of the eye. They make it to the retina where they’re then turned into electrical impulses that shoot along the optic nerve through the optic chiasm through the lateral cingulate nucleus and all the way to the visual cortex in the back of the brain where the image is processed and then on to assigning meaning and association. What do you know about that? What does that remind you of? You may have a conscious thought about it, but either way, the message then is sent down the vagus nerve to the stomach and stomach acid, stomach juices, gastric juices, begin to be formed. And this physical change in the body happens just from the sight of the pie.

[00:04:00] So the way it works —

[00:04:01] Number one: sensors transmit the environment to the brain. By the way, it’s not just a vision. A smell can do it. Touch can do it. The sound of bacon sizzling can do it. Even the word chocolate can do it. But sensors transmit the environment to the brain and the more sensors that are involved the stronger they are, the more powerful the transmission. So seeing it is one thing. If you see it and smell it both it’s a more profound response. Number one sensors transmit the environment to the brain.

[00:04:29] Number two: there may or may not be a conscious thought. And if there is is likely related to prior sensing of something.

[00:04:38] And Number three: the brain anticipates what’s about to happen, associates it with other memories you have in the past and experiences you’ve had simulates what’s about to happen and orchestrates a cascade of responses.

[00:04:53] Those responses are called C.P. R.s — Cephalic Phase Responses and there are lots of them. We just talked about one, the hydrochloric acid in the stomach, but you mix saliva, you make digestive enzymes in the mouth, you make immunoglobulin, the hydrochloric acid we talked about, gastro digestive enzymes, immunoglobulin, leptin, ghrelin, and bicarbonate, cholecystokinin and on, and on, and on.

[00:05:16] You secrete insulin before the first bite of food makes it into your mouth and the insulin amount varies depending on what the food is you’re salivating over.

[00:05:28] This cephalic phase response, this Brain Stage, where it plays out isn’t just in you and me. It’s so important to living things its also found in our primate cousins. They also have a rich varied Brain Stage of food. And not just them.

[00:05:51] Other mammals like dogs. In fact it was first worked out in dogs over 100 years ago by Pavlov who found that dogs would salivate. They would create the gastric juices when they saw food. But then if that experience was linked to a sound like a bell, or a buzzer, or a physical experience or a time of day, that would trigger the Cephalic Phase — they’d have the Brain Stage, just from the other thing [the trigger] — the bell ringing, even if the food wasn’t present.

[00:06:20] And it’s not just the mammals, it’s in birds. And even in the striped bass. It’s in fish as well as us.

[00:06:27] Just to put it in perspective up to 30 percent of all the gastric juices you secrete happen as part of the Brain Stage — not after the food gets the stomach. That means each of us we can make up to about 10 ounces a day of gastric juices just from cephalic phase. That’s what the Brain Stage is.

[00:06:53] Let’s talk about an edge case. Something that’s a food and also that’s a drug. And that edge case is coffee. Coffee is one of the most widely consumed beverages in the world. It’s got its own distinct flavor and aroma but it also has caffeine which is the number one most used psychoactive drug in the world.

[00:07:19] A few years ago some researchers in Norway decided to do a study where they they hook people up [to monitors] to look at all kinds of minor changes in their physiology — their skin conductance the heart rate heart rate variability and half of them were given coffee to drink and the other half were tricked and told they were getting coffee but there was really no caffeine in it. It was really decaf. And what they found was that at first was the ones who were tricked also had the heart rate changes, the skin conductance changes, and were more alert and had blood pressure changes. They were tricked into believing that it was actually coffee and responded like it was coffee — at least for a while, until the caffeine didn’t really show up.

[00:08:05] And they call this a placebo response.

[00:08:07] The idea behind a placebo is something that is given in a test that is actually ineffective, or at least not specifically effective, and it’s used to distinguish something from what the real effect is. In many medical studies, there is a placebo, on the one hand, and it’s supposed to not be effective.

[00:08:29] Then there’s the drug, on the other hand, so the idea of placebo versus drug is very common. But I take a different approach. What matters most is the placebo plus the drug. It’s the total effect of the experience and the medication. The total of the benefits, and some of the downsides.

[00:08:51] So let me tell you about another study that was done just with real coffee itself. People were set up with monitors that could detect changes immediately. With real coffee, and caffeine the drug, at the first sip of coffee, immediately the body began to change the heart rate went up. The level of alertness went up. It was immediate. You think about it when you swallow coffee.

[00:09:20] It has to takes eight or nine seconds to go down into the stomach and then it churns around there for a bit, it goes down to the intestines, it gets broken up into little bits, it gets absorbed. It could be half an hour before significant levels of caffeine make it into the bloodstream, but immediately they responded. So the actual thing [the real coffee] there was a Brain Stage that happened as part of the response. And on a minor side note, interestingly the way the Brain Stage worked was different than the way caffeine actually works. Caffeine works on some receptors called adenosine receptors and it delays tiredness, but the effect of the coffee that was studied ws found to be on bitter receptors — bitter taste receptors in aroma receptors and it worked on the vagus nerve to mimic the response of caffeine. The body wasn’t tricked. It knew what it was doing. And by the way, you can create that brain stage of coffee even just from the smell of coffee.

[00:10:18] In fact there are studies in animals showing that just by inhaling the aroma of coffee it can change the expression of 17 genes in the brain and change the levels of nine different proteins in the brain just from smelling it and it may go even a step further.

[00:10:38] There is a study that was done where they had half the people read a story about coffee. The other half read the same story but about tea. The ones who read about coffee the association was strong enough that their heart rates went up from that.

[00:10:54] So coffee is a drug. Coffee is a food. Coffee has a brain stage. So do other drugs. One really profound study was done in Italy where they took people who they came in and they were actually giving them powerful drugs, or powerful medication, medical treatments but they didn’t know when they got it.

[00:11:13] They were post-operative patients who were who had significant pain and half of them were told you’re getting morphine now. The other half weren’t told that. But they got the same amount of morphine and when they didn’t know they were getting morphine, it was less than half as effective. It was more than twice as effective if they were told. [Morphine is a] powerful drug, but there still a Brain Stage. That was a part of it. They didn’t know. Not as effective.

[00:11:41] Others got I.V. valium for severe anxiety after a procedure and the ones who were not told [they were getting it] there was not much effect. The ones who knew they were getting had a profound effect of a powerful drug. My take home is this — if I’m ever going to give a medication to someone, or do a treatment for someone, I really want them to know what we’re doing, why we’re doing it, why we expect it to work, and what we expect the effect to be because when we’re engaged with a treatment at the brain level we can get the full benefit of the best treatments.

[00:12:22] Point One was that every pill has a hidden Brain Stage.

[00:12:25] Point two: everything is a pill. And by pill here I just mean “something from the outside that has an impact on our health, that maintains our health, or enhances our health, or perhaps diminishes it”.

[00:12:40] So we’ve been talking medications. But surgery is a pill. Perhaps one of the most important pills.

[00:12:46] One of the studies that blew me away was [done by] a fabulous orthopedic surgeon at Baylor University. He was an orthopedic surgeon for an NBA team and for an Olympics team. he was doing arthroscopy on the knee of people who had osteoarthritis that had moderate to severe pain for six months, who had changes visible on X-ray, that hadn’t responded to the best medical treatment for at least six months. They signed up to be in the study to treat their osteoarthritic pain, lack of mobility, and to treat the gunk that was their knee. One hundred eighty people [in total]. About 60 of them were assigned to have state of the art surgery, which is where they insert the arthroscope. They would go in and shave and clean up the cartilage in the joint. They would flush [the knee with] saline to get rid of all the debris. About a third of the patients were gonna get that [treatment]. About a third of them were assigned to just get the knee flushed out. Maybe that would be enough to have close to the effect of the actual surgery. The final group was very interesting. It was just to get a baseline. They called it the placebo group. And what they did for them is no surgery at all.

[00:14:05] When the nurses brought them [into the operating room] nobody on the team knew which group the patient was in. They opened the envelope [identifying the group] after the patient was already unconscious. If the patient was in the no-surgery group, they made three one-centimeter incisions around the knee and they either played a tape with the noises of real operation or the surgeon would ask for the instruments, but they would do the same amount of time then move the knee around a little bit when they were talking about inserting something. They would splash it was saline when they talked about irrigating it but nothing went inside at all. At the end of the time, they sewed it up.

[00:14:38] Everybody got the same bandage. Everybody had the same post-operative pain meds. The people caring for them afterward didn’t know who was whom. They stayed in the same post-surgical setting and then they followed those people for two years and saw them seven different times over two years.

[00:14:59] And you might think that one group was better earlier, but two years out they weren’t that much different. Or maybe in the middle, they were different, but they all end up the same. Or maybe they end up wildly different at the end. But the answer was good news. The surgery worked. Shocking news. There was no meaningful difference between the three groups either short term, medium term, or long term either. And how they felt about pain, or how quickly they could walk 100 feet, or how quickly they could climb a flight of stairs. Zero difference.

[00:15:31] The Brain Stage is so powerful that that setting, that ceremonial impact, being in the operating room, and going through that journey could trigger the body to heal to the same extent as those who actually had the procedure.

[00:15:50] That’s not always the case but it’s a glimpse into how powerful the Brain Stage can be and you want to tap into that on top of the best treatments. Surgery is a pill.

[00:16:03] Connections are a pill. When we connect with one another it can be extraordinarily powerful. A touch, a glance, can relieve pain, can speed the healing process. When one spouse dies the other one can get a lot sicker.

[00:16:17] In pediatrics there was a story that I found rather interesting as a young practitioner — and up until recently. When a kid has croup at night they have swollen vocal cords and a barking cough. Often the parents are scared, the child is scared, and they will call the pediatrician or the answering service. They’ll be told to go to an urgent care center or emergency room and then the classic story is they bundle the child up and out they go out into the cold night air. By the time they get to the E.R. or their urgent care center the cough is a lot better and everyone relaxes.

[00:16:51] They said really they were sick before. And for the longest time, I believed that it was the cold night air that solved it. And it probably still helps, but since I’ve been part of a practice that does house calls I’ve seen another side of the story. The people call up, [the child has a barking cough] but instead of me sending them out I go to their home. By the time I get there they say, as soon as their child heard that the doctor’s coming, they started relaxing and by the time I get there and I examine them there’s tremendous improvement — often before I get there. With croup and with so many other things, connection is a pill and connection with an expert is a pill.

[00:17:35] There was a study in the New York Times in January of 2019 going through a series of studies that were done at Stanford. What they did is they injected histamine into the forearm of patients — something that will create a big red itchy, impressive welt, like in allergy skin testing. But in the first study, one group had a doctor come along at the right moment and truthfully say that from this point on it should start getting better. And the group that had that simple truthful statement did start getting better right then and faster. But the most important part of the suite of studies was that the language itself is good but the really powerful thing came from the nature of the interaction. The doctors that were clearly competent unrushed and caring had dramatically faster and better results than those who were perceived as incompetent or not connected or rushed. The nature of the relationship of your expert relationships matters.

[00:18:48] Speaking of nature, nature itself is a pill. There’s been a lot of research recently about how our environment impacts our health in short term and long term ways. There was a recent meta-analysis that was done of 20 different studies looking at blood pressure when you’re surrounded by nature and blood pressure systolic and diastolic blood pressures lower around nature. The Brain Stage of nature.

[00:19:15] And of course food is a pill. What we eat, what we even look at, and salivate at can impact our health in the short term and long in really profound ways.

[00:19:25] So again every pill has a hidden Brain Stage and everything is a pill.

[00:19:34] What you want to do about that —

[00:19:36] Number one: just in the same way that mindful eating is valuable. So is mindful medication. If you are taking a pill, or giving a pill, rather than just doing it mindlessly pause for just a moment and remember what it’s there for, what it’s supposed to do, what you expect it to do.

[00:19:56] Second if you are going to work with an expert, choose someone who is competent and caring that you can connect with.

[00:20:04] And third go for the very best medical treatments you can, but don’t miss out on the benefit by ignoring the Brain Stage. Start looking for it. It’s everywhere.

Dr. Alan Greene

Dr. Greene is a practicing physician, author, national and international TEDx speaker, and global health advocate. He is a graduate of Princeton University and University of California San Francisco.

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