The Truth About Headaches: Surprising Science & Groundbreaking Treatments | Tom Zeller Jr.

0:00Jonathan Fields: So headaches can literally derail your life. And sadly, I'm speaking from personal experience. They have been a part of my life since I was a teen, at times making it hard to function. And I'm not alone. For billions of people worldwide, headaches aren't just an inconvenience. They're an invisible force that can completely derail you without warning. What's fascinating is that until 2018, we didn't actually have a single medication specifically designed to prevent them. I mean, how is that even possible? Turns out there's a lot that we don't know and a lot of things that we are learning. So what if everything you thought you knew about headaches was wrong even?

0:36Jonathan Fields: That's where we're headed today. My guest, Tom Zeller Jr. is a former New York Times journalist, current editor-in-chief of the digital science magazine Undark, and the author of The Headache, The Science of a most confounding affliction and a search for relief. And Tom brings both personal experience and investigative rigor to this exploration of headaches, weaving together cutting-edge neuroscience, cultural history, and his own journey with cluster headaches, which are considered among the most intensely painful conditions human can experience. And what we uncover in this conversation, it might surprise you, from the complete absence of specifically designed preventative medications until just a few years ago, to the profound gender bias that has shaped treatment throughout history.

1:18Jonathan Fields: We explore emerging frontiers in treatment from AI-powered early warning systems to devices to pharma to psychedelic therapies and examine why the simple word headache may actually be holding back both research and understanding. So whether you experience headaches yourself or know someone who does, this conversation offers vital insights into an often invisible condition that impacts relationships, careers, and lives in ways most people never see. And what emerges is not just a deeper understanding of headache, but a window into really how we think about, treat, and talk about invisible pain.

1:53Jonathan Fields: So excited to share this conversation with you. I'm Jonathan Fields, and this is Good Life Project.

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3:53Jonathan Fields: Chicken that's just chicken, no trade-offs, no second guessing. Look for Nature Ray's Farms Chicken in your freezer aisle and get back to simply enjoying dinner. I think a good starting point for this conversation is sort of like the exploration of headaches is you. You've got a new book literally called The Headache. And this wasn't just an interesting journalistic exploration for you. This is deeply personal. So take me into that. So I mean, as anyone who reads the book will quickly find out, I myself have what's called cluster headache. It's less familiar, I think, to most people than say a classic migraine, which is probably the most familiar of all the primary headaches.

4:34But that was sort of the starting point for me. I started to develop these headaches in my 20s and cluster headaches are pretty painful. I try to avoid getting into comparative measures, but cluster headaches are considered one of the most painful syndromes that a human being can experience. So it would be foolish of me to try to explain the dialectic of my life without including the mark that these headaches have had on me. I never set out to, at least not in the first 30 years of my journalistic career, set out to tell that story. It was something that I always kind of kept very private. People around me knew that I had these headaches and necessarily some of my employers knew, although I took a lot of steps to sort of hide that behind a curtain as well, even from them.

5:26But when I finally decided to look into this as a book project, and we can talk about why that might've been too, but I started to realize that all of those characteristics, not just the pain, but the hiding, the sort of slight sense of shame or self-blame, the inability to really have serious conversations with people about it, the misunderstanding even within the medical community, attempts to hide it from employers, all of these things were like really, really common among a lot of the people that I talked to. That was like what pulled me onto this path, if you will.

6:00Jonathan Fields: One of my curiosities also, and I wanted to dive a lot more into the world of Hitting, But also, before we even get there, and you alluded to this, you have a long career as a journalist and a science writer, right? And part of the ethos of journalism is like, you're not the subject in the story. you know and and there is a there is a tradition of sort of you know like experiential journalism where i'm going to put myself in this mix and you're like michael pollan or and like i'm going to report from the front lines of my own personal experience i think that's still pretty much the outlier in that world where it's sort of like okay i'm going to go out and talk to all the people interview all the experts find out what and i'm going to report from the front lines of what's happening to others what i'm learning from others so you making a decision to say well i'm actually going to lead this and actually bring myself into this conversation.

6:47Jonathan Fields: I'm curious for you, just as a journalist, like how that was for you. It was terrible. It was absolutely terrible. It was terrifying. I resisted it in the beginning, kicking and screaming as I discussed it with my original editor. And yeah, it was as everything that you say described exactly how I felt as a journalist. I read about other people. I tried to take myself out of the story, especially a certain sort of journalism. I mean, you mentioned that there are exceptions, but I was, you know, spent the majority of my journalistic career at the New York Times where the voice from nowhere is sort of the default posture of storytelling at the New York Times.

7:24And you can debate whether or not that's a good posture or a bad posture, but it's the posture I learned. So, when my editor told me, well, we really need you to be a character in this book. I mean, obviously, I'm writing it because I have headaches, but I thought maybe that would be a paragraph in the book. And then the rest of it, I could spend my time. But he seemed really convinced that it couldn't be that, that I would only gain authority and also gain the trust of an audience for this book. If I was willing to unveil myself to and put myself into the story. So it was a struggle. And I, I had to learn how to do it and how to do it honestly, because, you know, your temptation is to still kind of shade and duck and weave even from yourself.

8:12So it was really hard. I'm glad you asked that because it's something that I think most readers probably wouldn't talk into. But if you're a journalist and spend any amount of time doing it, it's absolutely terrifying to write about yourself.

8:24Jonathan Fields: Yeah, and I'm not a journalist. I've written a number of books and the very first book I wrote, I didn't put myself in the story at all. And my editor came back to me. She's like, nah. She's like, especially the first book out, People want to know who you are. They want to have a sense for who you are and why they should care about what you're doing and what you have to say and what you're bringing to them. And I was deeply uncomfortable with that as well, just because I don't like that level of immersion of my own story. It's changed over the years, but it's an uncomfortable thing. I think no matter, for most people, it's really fairly uncomfortable.

9:00Do you think you're more comfortable with it now?

9:02Jonathan Fields: I am. And I think that's just literally, you know, it's 15 years of exposure therapy at this point. Yeah, I don't have enough yet. I've told people that my next book is going to be anything but about me, if I can help it. I've told friends on occasion, I said, you know, like, my ultimate aspiration is for me to become invisible and let the work to always take the lead. But it's a very hard thing to do, especially in the age that we're living in. Yeah, and I think book writing and book reading is such a different animal in some ways. You know, I'm an avid reader, but I'd never really attempted a book before.

9:36And I think I learned that, you know, that there's a different transaction happening than in other kinds of writing that it's very intimate. It's the longest of forms. You're going on this journey together. And so in the same way that you might expect your seatmate on a cross country drive to open up to you, you sort of or you're yeah, you expect the driver to open up to you on that long ride. Yeah.

9:59Jonathan Fields: And it's sort of like you have to answer the question out of the gate. Why should I trust you enough to give you six or eight or 10 hours of my time in a world where it seems like I just don't have enough anyway? Yeah. Yeah. So let's drop into the world of headache again. So as you described, you have had cluster headaches since your 20s. Headache is an interesting term. It's this big catch-all. It's a giant bucket. And into that bucket, people have maybe heard clusters. I'm sure a lot of people have heard migraine, tension, headaches. How do we distinguish between the types of headaches these days?

10:35That's sort of a double-edged question in a way, because how do we distinguish between the headaches medically is a very different question from how do we distinguish between headaches culturally. And I think that that matters in some ways. And in a lot of ways, the culture has influenced medicine too. And I get into some of that in the book. So, I mean, the quick headline description of medical headaches are that there are headaches that are symptoms of some other malady. So, you might develop a headache as a byproduct of, say, a COVID infection or being dehydrated, having too much to drink the night before.

11:10We can discern what the cause of those headaches are. And then there are primary headaches. This is what they're called in the medical literature. And these are headaches that are idiopathic. They are diseases unto themselves without any known cause. So migraine is probably the most familiar one. You named tension headache. Tension headache is probably the most common one, but they tend to be less severe and can often be treated. I don't want to diminish anyone's experience with these, but they can often be treated with over-the-counter medications or some lifestyle changes. Not always, and they can be ruinous in their own way, but they're the most common.

11:48Then migraine. I mean, I learned just staggering numbers of people, primarily women, have migraines, something like 50 million just in the US alone. And then cluster headaches is the third of the major primary headaches. And then there are several others that are less familiar, thunderclap headaches. There's even orgasm headaches, which are spontaneous headaches that come on at the point of orgasm. That's how it's sort of parsed up medically. In the culture, it's a much more interesting question because we use this word headache metaphorically for all kinds of things, you know, for an annoyance, for things that are just driving us nuts, things that we don't want to do.

12:30And we all use that term and we all recognize it. I've even seen uses of the term migraine as a synonym in that very sense, not as a medical headache, but as, boy, these taxes are a real migraine. And I think the fact that we traffic in those terms that way has made it harder for people with the medically parsed version of the disorder to really gain any sort of attention, whether it's, you know, financially from the National Institutes of Health or from, you know, an employer who might think that you're sort of, I don't want to say faking it, but we've all had headaches. We all know what headaches are.

13:07And it becomes very hard to convince someone, or at least that's the feeling that I think that people with headaches take in. Maybe it's not fair to, it's something that we internalize, but there's a sense that everyone's had a headache. And if it's bringing you down, then it's, you're the weak one. I have headaches too, and it doesn't bring me down. So what's wrong with you? There's sort of that implied judgment. Is it fair? I don't know. You tell me you've had headaches.

13:35Jonathan Fields: I think it's really interesting because earlier in our conversation, you said, I'm not going to compare my cluster headaches to somebody else. I can't tell you what my relative level of pain is compared to somebody else, either with their type of headache or whatever it is they may be going through. And I sense that that's one of the really big challenges with people who suffer headaches is that you've got two people both told that the pain that they're experiencing, here's a checklist, okay, that qualifies as a migraine, right? One person's like, all right, I can kind of work through it. It sucks, but I'll deal with it.

14:08Jonathan Fields: Another person is leveled with it, can't get out of bed, can't be around sound, can't be around light, and maybe it takes three days to wash out of their system. And yet you hear two people side by side saying, like, you've got migraines. So, yeah, you can see how there might be a tendency for somebody, depending on their social conditioning over late with that, also to kind of say the other one, like, come on, buck up. Or somebody who has regular tension headaches. You know, like, come on, seriously, like, look, I have these all the time. You got to deal with it. And there's this whole social and judgmental overlay that happens that I think, and you write about this, that makes the actual pure headache related pain potentially compounded.

14:49Yes. And I think that there's, there are a few things that work there. You know, we can probably, if we take the population in aggregate, you can always be assured that some small percentage of them will be classic malingerers or they might be hypochondriacs or, you know, and that's, I even state this in the book. I think that's okay. I mean, whatever field distortion has you showing up at the doorstep of a doc seeking help deserves empathy and deserves attention. But we can step back from that and honestly assume that some percentage of people just have something else going on and the pain is just their way of addressing it.

15:29But it beggars belief to think that someone who is retreating to the bedroom, missing their daughter's wedding, missing functions at work, almost transforming from a person who's just really engaged, social, extroverted, and then retreating into a dark room for days at a time, it beggars belief that any large percentage of them are not in anything but terrible pain. And yet, and yet, it's because of that word headache, and because of the dynamics that you're describing, that residue, I think, tends to sort of be there either overtly or not. I mean, I've struggled even with the book to decide how much of this am I just kind of internalizing from the wider culture and then imposing on myself versus how much is really sort of being directly projected at me by people in my life.

16:19I think far fewer in the latter case, but you feel it anyway. I mean, I'd be curious to know if you ever, I mean, I would guess that with your headache, what kind of headaches do you have?

16:29Jonathan Fields: I have migraines, I have tension headaches, I have ocular headaches. So I have like a nice, a nice little collection of fun things that kind of like have a rotation with me. Do you get the neurological accompanying symptoms with your migraines, like the aura? Very rarely. And the only reason I would even know how to answer that question is because literally decades ago, one time I got the classic, the aura, the spotty vision, and I didn't have a headache. But somebody who was familiar with migraine asked me way back then, they're like, do you have a headache? I was like, no. And they're like, you may want to go home now.

17:00Jonathan Fields: And sure enough, 20 minutes later, I was flat out for the next 24 hours. Yeah. And flat out because the pain was one, the major symptom, the salient symptom for you was just yeah yeah was that something that you wanted to talk about readily with with people no no and this is one of the things you write about right also is just like and we not too long ago we did a whole episode and sort of like invisible pain especially chronic invisible pain when other people can't see it it's really hard for you to know like you want there's this tendency to hide it because you feel like you're going to be judged for you won't be believed and then other people kind of look at you like, I don't know, you look okay.

17:41Yeah, you seem fine. I mean, there is so much bound up in the credibility of a wound, right? If I can show you this thing that's causing me the pain, then I suddenly gain a coin of credibility that people with headache and other kinds of invisible pain, and I mentioned some of them in the book too, yeah, just can never get. Their pockets are always empty on that front. And so, I think that that's why we, you know, there's a certain shame factor in, I think, attending headaches. I think some of it has to do with, we would be remiss if we didn't mention that, you know, most migraineurs are women, like, I think by three to one.

18:19Not all. I mean, men obviously get migraines too. And, but it's almost certainly a hormonal component happening there. And when we can't figure out, historically in medicine, when we can't figure out what's ailing a woman, it's because she's hysterical that's that's what we've tended to sort of describe it as and that is sort of that blended out i think through the culture over the last 200 years to define headache writ large if you seem fine so you must it must all be in your head there is this really interesting

18:50Jonathan Fields: gender overlay there if over the last couple hundred years like women experiences on a three to one basis meaning they're the ones who are most likely to seek help for it i would imagine or at least in the beginning. And then because it's nothing observable, there is this gender bias and there's the sort of like the classic labeling of, you know, it's gaslighting, medical gaslighting saying, well. Exactly. Then you sort of expand that out into the culture and then there's association. Well, like pretty much maybe most people who had this thing going on then, you know, it's just, there's other stuff in their life.

19:25Jonathan Fields: They're making it up, whatever's going on. Like it's not a real thing. Yeah, yeah. it's not a real thing. Or, you know, the classic, you just need to relax, you're too high strung. I mean, there's a whole rich tradition of comical but terrible literature from the mid 20th century, depicting women with migraine as being frigid. If they would just have sex with their husbands more, their headaches would go away. I mean, and this was literally advice being dispensed by physicians in popular magazines and newspapers. And interestingly, even at the time, and there are some really good books that sort of cover this in greater depth than mine.

20:04Joanna Kempner is one author that anyone interested should look that up. I think her first book is called Not Tonight. And she gets into this pretty deeply. But men during the same period who have migraines or complained of migraines or were diagnosed with migraines were described with a whole other typology. They were too success-driven. They were too ambitious, and they were too intelligent. But women were described with the same condition as being too frigid and too stressed. So, I mean, the sort of gender biases are obvious. And we've obviously grown beyond that, but there's still a residue.

20:43There are anecdotes in the book where I spoke to women who still experience some semblance of this in the privacy of their doctor's offices today in 2025.

20:53Jonathan Fields: There's an impact there. If you show up and you're in pain, then somebody tells you it's not real. Then you're also showing up with your history, with your psychology, with your patterning, your conditioning, your traumas. And you may then bring to that pronouncement, okay, this is a person of authority. It must be right. And then whatever wounding you're bringing to that and the shame and the blame saying, well, maybe this is my fault. Maybe then you take the actual physiological pain and you compound it with just like psychological heaviness that creates this really awful spiral. Yeah, a terrible spiral.

21:32And it also complicates the way that we talk about things that do, I mean, actually have probably some role to play in migraines and maybe cluster headache too, which is that these are very sort of chemically driven, mechanistic in a way that is still somewhat invisible to us. We're still trying to figure it out, but almost certainly a neurobiological disorder, a breakdown of a sensory system that can be exacerbated by stress, for example. But it makes it harder to talk about that stress as a hormonal event, a release of cortisol or release of other hormones that can interact with certain receptors and exacerbate pain.

22:16It's not a clean linear connection, but it certainly plays a role. But if you're telling me that I suffer from this disease because I'm a stress case, you make it really hard to have sophisticated conversations about hormone wash and the tides of our blood system in a meaningful way that isn't sort of dripping with bias and judgment and simplicity.

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26:31Jonathan Fields: and there seem to be evolving theories about what is actually at the root of pain in your head. I mean, I have to tell you, I started out in some way driven by the fact that this surely must be noble. This surely must be something that, you know, a headache. In some ways, we know more about the common cold than we know about headaches. So, I started out probably a bit naively thinking, well, if I just talk to the right neuroscientists, they will lead me down the molecular pathway that leads to pain. And surely, I think even most of us who have never investigated this, if asked, would probably say, well, blood vessels in my head are throbbing, they're bumping up, they're mashing up against a nerve ending somehow, and that's generating pain.

27:20I think probably a lot of us would think if we were asked to describe what is going on in a headache, we would say that. And for hundreds of years, that was sort of the prevailing theory. I mean, there were other flavors and other explanations that involved the humors, but there was a general sense that the flow of blood into the brain had some major role to play. We don't know in 2025 that's necessarily true. And one of the most entertaining things for me as a signage journalist was to talk to experts from different camps on this question because they vigorously disagree with each other on the role that the blood vessels play at all in headache.

28:02So, if I were to give my best guess of what a typical neurologist would say that isn't necessarily caught up on the latest literature, they would say, well, it's probably an activation of the blood vessels in the meninges, which is the the only enervated part of the brain. It's the layer between the skull and the gray matter itself. It's the only thing that could experience pain, they would say. So, it must be something to do with the blood vessels and the nerves in that layer of the brain. And probably if they know a little bit more, they would say the trigeminal nerve, which is the nerve that provides sensation to your face and parts of the sides of your head is mixed up in this business somehow.

28:52There'd be some disagreement over whether or not that's the trigger, if that's where it starts. But certainly we know that certain molecules are released from the trigeminal nerve neurotransmitters during a headache event. So we certainly know that it's involved. And that has led to some interesting therapies, which I'm sure we'll talk about. And they would probably say, if they knew even a little bit more, that the hypothalamus is probably a central player in this, although we couldn't say exactly how. Is it the prime mover? Does something go wrong in the hypothalamus and then set everything off and then trigger that inflammation in the meninges?

29:30We don't know for sure. And then I would say if they were really at the cutting edge and maybe even playing at the fringe of headache science, they would say everybody's wrong. There have been plenty of studies that show that the blood vessels are not activated at all in some people experiencing a migraine attack or a cluster attack. There have been studies, there was a classical study of a cluster headache patient for whom it's just almost axiomatic that the trigeminal nerve is a central player in this, who had that nerve severed at the point during a surgical severing to relieve his pain. And he still had cluster headaches.

30:09So if a scientist was really at the edge of things, they would say, we really absolutely don't know. We know all these structures are involved. We know there's chemistry involved, but we don't know why. And we don't know why it persists in the human animal almost uniquely, probably in the animal kingdom. I mean, we don't really have good evidence that other animals sort of fall over and hold their heads very often. Maybe we're just not seeing it, but probably unique to the human animal and something that probably should have evolved out of the human animal by now. So there's a lot of discussion and interest in why this thing also persists.

30:48So that's probably a long-winded explanation, mechanistic sort of description, the best I could do.

30:53Jonathan Fields: But it's really interesting, right? Because you're describing a scenario where this is something that affects a huge percentage of the population. It has affected a huge percentage of the population for generations. and yet we're still largely at a loss to understand the source. Like, where is this actually coming from? And the theories that became prevailing theories are now really kind of like on the way out. And there's all this, as you described, there's all this research. This is, but we literally can look into somebody's head, like in the middle of a pain bout and see that this is not happening.

31:29Jonathan Fields: You know, it can't really be the thing. Yes. And I think that that's what's really confounding for that. I mean, on some level, you know, you have to allow that the brain is an incredibly complex organ, the most complex, and really, really hard to study while subjects are still using them. You know, in some ways, it makes some sense. But I do think that a lot of the sort of presumption and paradigm stasis and bias in earlier eras contributed to our ignorance now. Wow. One thing that we probably should mention is that it's not just the culture, or it's just not ordinary people carrying around these judgments about headache.

32:11One byproduct, I think, of the weird bias that migraine brings with it is that even among neurologists and neuroscientists, it's kind of considered not a sexy thing to study, you know, and they're kind of embarrassed by it. I talked to researchers who were deeply interested in studying headaches, but were told by colleagues, yeah, you don't want to do that. It's not a big problem. Headache patients are a pain to deal with. You don't want to mess with that. And they're discouraged. They're discouraged from going into it. And I think that too is residue of a sort of bias that we carry as a culture and also why we remain as ignorant as we are.

32:54Jonathan Fields: Yeah. It's like if your primary researchers are discovered from really allocating time, money, and energy to it, it slows the whole process of understanding what's really going on. And then in turn, the entire process of either treatment and or cure at some point. Yeah. It seems really reasonable. If you've got a population in the tens of millions, probably a billion worldwide the amount of economic drain that these conditions represent is just staggering it's almost laughable when you start to dig into the numbers and realize just how much missed work how much missed consumerism how much missed life there is because of these absolutely debilitating conditions and they are debilitating i mean it sounds like an overstatement and i was sort of hesitant when i first started writing the book to talk about it in those terms But I think even the World Health Organization considers someone in the throes of a migraine to be as disabled as quadriplegic.

33:53I mean, they actually use those terms, which I recoiled from that analogy at first because it seems absurd and it seems to be stealing something from – it's just a headache. It can't compare a headache to quadriplegia, right? But if you break it down, I mean, in the throes, when you were laid out with that migraine that you had that was just so painful, you couldn't do anything, could you? I mean, you were functionally disabled during that period.

34:21Jonathan Fields: I wouldn't personally make the analogy to say that, okay, so I have the equivalent functionality of somebody who is experiencing quadriplegia, but has it been profoundly disabling for short moments of time in my life? Yes. And I'm probably not at the extreme pain end of the spectrum given people, even within my own orbit, who I know who experienced it on just a completely different level from me, but it makes it so that you can function. And it's this really weird transient disability, whereas, you know, you're like, you're forever cured, you know, in most cases. I mean, some people do have chronic forms of the disease, which I can't even imagine.

35:01But, you know, for most people, it comes and it goes. So you're disabled, and then you're not. Or you're, you know, if you're not fully disabled, you're certainly diminished, and then you're not. And to some extent, that also has contributed to a sense that, well, this isn't something that we really should spend any money on, despite the fact that were you to introduce a cure for headaches writ large, just prevent them from happening. The amount of sheer economic benefit from that would be absolutely staggering on the order of whole GDPs of some countries.

35:35Jonathan Fields: On top of just like the lessening of suffering on a scale that is astonishing. Of course. There's something I'm really curious about and wonder if you came across any research in your exploration. So a million years ago, I used to teach yoga in New York City and there would be nights where 6.30 would come, I'd show up at my studio, there would be a packed room full of like 50 people mat to mat and they're expecting me to show up and give them 90 minutes that will be worth the time they just gave me. and my head would be pounding, absolutely pounding. I was in the middle of a migraine. I could turn down the lights.

36:11Jonathan Fields: I could sort of like adjust. And I noticed a weird thing happened pretty often, right? I would walk up and then I would walk into the room. My head is pounding, but this was my job. And I own the studio also. So it was sort of like, you know, this is just, I had to quote, suck it up. This is what I do, right? People were expecting this of me. So I went in. And then I began to notice this repeated pattern, which is that I get a couple minutes into teaching the last class, and all of a sudden, I'd be like, oh, my head is pounding again. And it got me really curious about the role of attention in the experience of headache pain.

36:48Jonathan Fields: And I know attention, just in general, chronic pain, there can be a really strong association. But it was almost like when I stepped in, I said, this is my job. I need to be utterly present here. I need to just completely shift my attention outward to these people in a room and lose myself in that moment that for all intents and purposes, I did not have a headache. But the moment that my attention, the last person left that my attention shifted back into me, it was there again. I'm curious what your take is on that from the research that you've done, the people you've talked to. There is a fair amount of decent evidence, I think, that cognitive behavioral therapy, for instance, works for some people.

37:31I don't think it works for all people, but there is some amount of that research that suggests that you can will yourself, some people can, will themselves to a place where they either are able to calm that pain or set it up of a frame of reference enough that they're able to function without it. They're doing that consciously. It sounds to me like you were doing it unconsciously in some way. Right.

37:57Jonathan Fields: Yeah. And at the same time, like at that point, I had already started to develop a pretty dedicated meditation practice. So like I had a practice of directing my attention and holding it in a particular way. And I wasn't consciously trying to do that. But what I was consciously doing was saying, I know where my attention needs to be for this fixed window of time and I need to give it all. Yeah. And it was almost like there was no room for the pain while I was doing that. Yeah. And, you know, I think that that's A, congratulations. it's extraordinary that you're able to do that because i i think a lot of people there's a part of me that you know here's your story and doesn't want to suggest to listeners who could never do that in a million years totally get it either because i that that this is something that they could think themselves out of because in some ways that does tend to shift it back you know a certain amount of responsibility for the disease back onto the patient in a way that i'm loath to do.

38:53Jonathan Fields: And I'm with you. The last thing I would either of us want to do is sort of like shame and blame somebody for not being able to have this experience. At the same time, I think that there is a natural tendency, I think, when we experience pain. I mean, I would add the caveat in my case with the pain of a cluster headache. I will allow and issue the caveat that I can't know how anyone else would experience a cluster headache, but I experienced lots of kinds of pain in my life. I've had terrible ankle surgery. I've practically broken an ankle while running. I've had any measure of painful experiences, but this is a category difference.

39:30And on the intensity scale of, I would not be able to do what you did. And I would be literally on the floor, just writhing. It's, to me, it's very much like the intensity of a pain that you might get from having your hand on a hot burner. It's that level, but not stop. You can't take your hand off the burner. I'm not sure I could even gather thoughts. I couldn't gather thoughts to focus on something else. That said, the idea that we try to distract our attention from the pain is so native to the experience of pain in the human animal, which is why people often do self-harm in other ways during the throes of a really serious attack, both migraineurs and cluster patients.

40:16But I would, you know, I've never talked about this out loud, but you know, yeah, I would grind, you know, in the experience while having the headache, I would sometimes grind my fingers into my scalp in the spot where the pain was to the point where, you know, I'd be bleeding and in an attempt, and it does actually, I don't want to say help, but it's a distraction. You're focusing your attention on other stimuli in the body. I don't think though that, you know, a classical migraine or a cluster headache, the molecular sort of event that's happening, the neurological event that is happening is dominant and almost impossible to just look away from.

40:56I think what your experience is pretty remarkable, but I also think that it does have affinities with, you know, they try to teach this. I visited facilities where cognitive behavioral therapy and grabbing control of pain and trying to refocus it is a very common strategy. And for some people, it really does work. And I think it probably has something to do with the level of intensity of the pain at some point, you know. I'm sure it does, yeah. If there was a dagger going through your head at the beginning of that yoga class, you probably couldn't think your way out of it, I'm guessing. But maybe you could.

41:35Jonathan Fields: I don't know. I agree. And I think that's probably right. And we'll be right back after a word from our sponsors. Your Life Project is sponsored by Whatnot. So when I found Whatnot, probably a couple months ago now, I was just instantly hooked. I went on, I was looking for a couple of vinyl albums, ended up in this live chat with the seller and like 37 other people. Everybody's there just kind of sharing their love of old albums and buying these amazing finds. It felt less like shopping and more like a fun running conversation. And I walked away with exactly what I wanted and the prices weren't anywhere close to full price.

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44:04Jonathan Fields: Let's shift gears a little bit and talk about treatment because there are a number of different ways that we approach headache. Let's start out by talking a little bit about the pharma because I think that's a go-to for most people in the beginning or else like that's the first thing is that they try. Beyond whatever is over the counter, which may for some, depending on what they're experiencing, help in some way. But I think after that, the next thing is, okay, so like what might be prescribed to me? And there are a handful of common medications that work in varying degrees. So take me into this a bit.

44:37Yeah. So, I mean, the most interesting thing to me that I discovered, and I guess I sort of knew this intuitively, is that there are up until just a few years ago, and by few, I mean five, six years ago, there were no medications on the market at all that were expressly developed to treat a migraine headache or to treat a cluster headache in a preventative way. There was one in the 1960s that was incredibly toxic, a methisergide, which is now no longer prescribed, although it does have some clinical use, but it also created all kinds of nasty side effects. And then every other drug that's been prescribed, and in my case, for instance, it would be verapamil, which is a calcium channel blocker, also very common prescription for migraine patients.

45:28Topiramate, which is strangely an anti-epileptic drug that seemed to have some affinity or seemed to help some migraine patients for reasons that we couldn't explain, also became a default prescription for migraine patients and for cluster patients. And up until, say, the 1990s, that kind of was it. You might get caffeine pills. Cafragot was a common migraine prescription. And then in the 1990s, there was a wonderful discovery of sumatriptan, which is a drug. If you have migraines, I would guess you've probably been prescribed at least ones. Does it work for you? Ish. Ish. Okay. Yeah. It does work for a lot of people, but not everyone.

46:13And one thing that I learned in doing this, because I hadn't really covered pharma before, but if it works for about half of people, which is a roll of the dice, really, that's considered a sensational, sensational drug discovery. If it works for 60 % of people, you've struggled. And yet, for any given patient, it's a crapshoot. which seemed really pathetic to me, but that's really what we've been looking at. Sumatriptan was a great discovery. It sort of grew out of a lot of interest in serotonin, which we were only starting to learn anything about in the 50s and 60s. In the 70s, we started to isolate some receptors in the brain that seemed to have an affinity for this molecule that it was Dyslaxo, who was looking at it, seemed to have some interaction with head pain in a way that we couldn't explain, but did seem to work.

47:06So in the 1990s, we got, it was called Imatrex at the time, which is, it's now generic. And the drug was Sumatriptan and it was great. And it was a way to treat an individual migraine or cluster attack. I couldn't take it by pill because it just didn't work fast enough. You know, a cluster headache comes on in seconds with no warning. and to wait for a pill to take effect would not be the most effective therapy. But anyway, that drug was great and it worked well enough for some people, but it didn't really solve anything and it certainly didn't prevent headaches, which is part of the problem. So you can't keep popping sumatriptan because eventually you'll get the body adapts and you get into this terrible cycle of relapse headaches.

47:53So the sumatriptan wears off and now you've got a really massive and even worse migraine than before. You take another septumletriptan and you're caught in a cycle that's just miserable for folks. So even by the 1990s, 2000s, 2010, we didn't have anything to prevent a migraine or a cluster headache.

48:12Jonathan Fields: Yeah, which again is pretty stunning just giving the prevalence and the impact. Yeah, yeah. But behind the scenes, there was some swashbuckling science going on that we don't read about. And in some ways, despite the funding profile that headache has enjoyed or not enjoyed for the last many decades. I mean, it tends to be wildly underfunded. And so this research, if it gets done at all, is usually funded by industry anyway, and only if they have a hopeful target. And they started to have one in the 90s and 2000s in a molecule called CGRP, which is calcitonin gene-related peptide. And it's basically a neurotransmitter that was discovered in the 80s.

48:54And through some really interesting experiments, some scientists in Europe and in the United States figured out that during the throes of an attack, the blood seems to become awash in this strange CGRP molecule. And enough of them were curious to know why that they developed an antibody, unlike a typical like synthesized chemical medication these are biologics that you know they developed large molecule stuff that are very very very like uniquely targeted to just this receptor for cgrp and lo and behold a lot of people that in early testing stopped having migraine headaches it was almost kind of miraculous like they would you know it wasn't this was not treating the pain of a headache it was preventing women particularly who had had 15 16 terrible grinding migraine days a month, suddenly gone for the first times in their lives.

49:52And I talked to people for whom it was like awakenings. I mean, they just were like, this is like, I have my life back. And all of it, you know, tied to that really curious, interesting CGRP molecule that until 2018, which is the first time this stuff hit the market, had never really been commercialized into a medication. So it was sort of a very hopeful moment. And I think we're still in that hopeful moment in that there are now scientists who are trying to figure out, is there a more consequential molecule that we could be targeting that would be more universal? Or is there some sort of mechanism or receptor further downstream that would work for not just 50 % or 60 % or 70 % of people, but maybe all?

50:37And that's what they're working on now. So it's actually a really great time to have a headache. Yeah.

50:42Jonathan Fields: Yeah. I mean, it's really interesting. I've gone through the whole cycle. I currently take an anti-CGRP as an injection on a monthly basis. And I was very doubtful because I have a lot of history of things not working all that well for me. So I kind of hesitantly said, all right, I'll do this. And sure enough, like three months in, I was like, wait a minute, I'm barely ever getting headaches anymore. And I was like, I don't believe this because because maybe my sleep is better. Maybe my stress is a little better. Maybe my nutrition is better. And it took a while for me to be like, no, this is actually the major thing that's different right now.

51:21Jonathan Fields: And it was, I still have a quote, rescue med if I really need it. But it's also, it's a one-time version of that same thing. Yeah. And it is miraculous. It's kind of miraculous. And you, you know, you may well be, you know, there's still a lot of disagreement within industry and among neuroscientists as to like, what is the real world efficacy rate of these CGRP meds? And the more I talk to people, I mean, you talk to some and they're just like, it's a miracle. All my patients are being cured by this. But the more you talk to people and the more you sort of look at survey data, it starts to kind of ratchet down closer to that 50 % mark that has been true of a lot of medications, maybe a little bit better.

52:06But the saline takeaway, I think, is that there is this group of people who are super responders. Not only does the CGRP stuff work, it really, really works for people who have the genetic makeup that we don't fully understand. And you might well be one of them, and I might be too. For a cluster, you don't take it on as an ongoing basis. You take it a larger set of injections at the first sign of an attack. it's characteristic of cluster headaches to last for roughly two or three months of daily multiple grinding headaches and then disappear entirely so you just take it enough to stop that cycle and then don't take it again and i was as skeptical as you i've tried so much weird stuff in my life it's not much weirder for me to inject this stuff into my bum and hope for the best but i didn't think that it really was going to make a difference but i believe it did i believe it did for the first time in my life stop a cycle of cluster headaches from coming on the big question marks with cgrp is like you're taking it on the regular you know what are the byproducts of suppressing cgrp to that extent for long periods of time we don't know i mean those those questions aren't answered there is some evidence that even among super responders that the effect starts to wear off over time.

53:25So how long have you been taking? For me, it's less than a year. It's fairly new. So yeah. It's fairly new. Yeah. But there is some evidence and it's not, you know, bulletproof, but there is some evidence to suggest that after a few years, they start coming back and the CGRP, it sort of some patients who have been taking it since 2018 are now finding themselves sort of back to the drawing board and really kind of a heartbreaking way, to be honest.

53:54Jonathan Fields: I would imagine because you kind of think, oh, wow, like this is it. I'm good. And all of a sudden it's back. I want to talk about another category of interventions and treatments, which I think is really fascinating, like neuromodulation devices. And this seems to be sort of like this new wave of actual devices. So this is like a less invasive type of thing where instead of taking something that's going to alter your internal chemistry, there's something that you generally wear or put on on the outside or go for a treatment. Take me into this category of neuromodulators and devices. I have to say, I've not personally tried any of them, but I've talked to a lot of patients who have and swear by them.

54:35And I've talked to a lot of doctors who prescribe them and who more or less think whatever works, whatever gets you through the night, If it's working for someone, God bless. That said, the theory behind them has a lot of science behind it. I mean, to the extent that headaches are presumed to be at least in large part, if not in whole part, neurological. So there's a signaling process going awry. It stands to reason that if you can interrupt that signaling process in some way through an electrical stimulation, you might get some pain relief. So there's the Cephali device, which is, it almost looks like a, I think of ISIS when I imagine it.

55:15It's a bit of a crown with a diamond that sits on your forehead and it sends electrical signals into the nerves of the face. And in some people, this helps interrupt the pain of a migraine headache. The vagus nerve, which I'm sure you've read a lot about and probably even discussed on the show, is a really prominent superhighway for sending signals up and down throughout the body, particularly from the gut. And there is some sense that there is a gut-brain connection that has information for us on migraines too, although we don't fully understand it. But these devices can be held to the neck and it'll send electromagnetic signals into the vagus nerve.

55:56And in some patients, it does seem to help alleviate a headache. There are some that go on the back of the neck. There's a whole forest of them. There's one now that attaches to the arm, strangely enough, and travels up the nerves on the inner part of the arm. That seems really among the most promising of the ones that I've heard and read about. I don't think that there's a lot of – there's not a lot of clinical data to go on. Most of these are developed by device makers who have different hoops that they have to jump through at the FDA. So we have to take the studies that they produce at face value.

56:32I'm not saying that they're faked or anything, but is it the best, most robust set of data out there on any of these devices? No. so there's a part of me that seems that remains somewhat skeptical of them as any sort of universal i'm going to catch hell for saying this as some sort of universal solution for people that said it clearly works for some people and if it works for you then i think that you need to ask no more questions and just kind of yeah carry on and this is something by the way i'll mention that there's some evidence even in ancient times that we understood that electrical shock can have some interaction with the brain and head.

57:17So there's some speculation that even as far back as ancient Mesopotamia, we had some idea that an electric shock could help a headache. So it's not crazy that we would think this stuff could work.

57:29Jonathan Fields: And if you buy into the notion that there is some sort of electrical wiring issue, that's happening that's like at least contributing in a major way, then if there's a way to alter that electrical process, okay. Absolutely. So whether we're talking about, you know, like pharmaceutical intervention, devices, it's still kind of like, you know what, try it all until you find something that works. Because we can't point to any one thing and say like, I have a high expectation this is going to work for you and what you're experiencing. Which is, on the one hand, well, how cool. There are a whole a bunch of different things that I can try.

58:05Jonathan Fields: And there's like a universe of possibilities here. But on the other hand, potentially just really frustrating because if you start to ratchet through and you're trying it and you're really giving it your all, it's like, nope, not this. And then you go to the next one. Nope, not this. Then you go to the fancy devices. Nope, not this one, this one, this one. And then you're taking time, you're spending money. Oftentimes the newer things, whether it's pharma or a device, they're not covered by insurance or you have to really fight with insurance to get some level of coverage. So it's time and also like not infrequently a fair amount of money.

58:37Jonathan Fields: And you have no idea if it's going to help until you actually do the thing. Yeah. Such is the journey of a lot of people with headaches. I mean, they are one data point that emerged for me in the book was that headache tends to strike people in the prime of their life, right? In their most productive years, it often starts in puberty or shortly thereafter, and often enough tends to wane for a lot of patients as they reach middle age or their elder years. And the rates of polypharmacy among that population, who otherwise should be sort of in their most robust years of their lives, are commensurate with geriatric populations in terms of the amounts and numbers of overlapping drugs that they're taking just in order to find relief.

59:24Many patients are taking six, seven different kinds of drugs, using devices, overlapping, just to try to make it through the day and piece together an existence. And that's the grim tableau that I think a lot of headache patients face. I don't want to conclude on such a grim note, because I do think there is a lot of interesting science happening. But in some ways, the takeaway from the book, I think would be it's happening finally, and in spite of a lot of headwaters that had to be overcome.

59:53Jonathan Fields: And also, as we have this conversation, compared to if we had had this conversation a decade ago, 10 years ago, there's a lot more that is available to explore today. And it feels like the pace is accelerating, whether it's through funding, which is, as you described, a challenge, whether it's through private industry or now device makers. And I would imagine that AI is going to play a really interesting role in the development of new ideas, new treatments. and solutions. Incredible ideas. Yeah. Can I share one anecdote on the AI front? Yeah, yeah. One of the main guys that I talked to is a researcher from UCLA is developing a camera.

1:00:35It would be on your computer that looks at you throughout your workday. And through the use of AI training would be able to know, it would alert you just by looking at you that you're going to have a migraine in three days. So it can detect, That's sort of the goal and that's what they're working towards. But there is some evidence that that might come to pass because these AI models are able to detect subtle fluctuations and skin temperature and blood pulsation just by watching your skin move. And there's some good evidence that your migraine, anytime you get one, started developing as a storm several days before.

1:01:15So yeah, AI is going to have some fascinating roles to play in all this.

1:01:18Jonathan Fields: Yeah. I mean, imagine you pair that with sort of like a camera and then you've got a wearable on that's like reporting and a whole bunch of different things where you can't, you know, it's like when people were reporting that certain wearables were actually able to detect, you know, during COVID three or four days before any symptoms appeared when somebody had a high likelihood of actually like getting that. and I'm excited about the future of integrating things. Then we go from, and then we'll wrap up shortly after this. We also go from AI, which is the absolute cutting edge. We don't know what's coming, but it's happening so fast.

1:01:50Jonathan Fields: And then we go way back in time to psychedelics and interesting research being done in particular around psilocybin and headaches right now. Yeah, and that's sort of how the book starts is I've known for a while that this was percolating. It's particularly useful, or at least it's experimented with in the population of cluster headache patients who really were sort of the driving force behind science on this. So this is really interesting story of ground up science. This is another Joanna Kempner book. I keep plugging her books, but she has a book out now that's about this group of cluster headache patients who saw that psychedelics were helping them with their headaches and created this online culture where they came up with a regimen that seemed to work for a lot of people and then brought it to researchers at Harvard and said, you should look into this.

1:02:41you should look into this. And finally, some researchers listened. But at the end of the day, it makes some sense because you're playing around with the same serotogenic receptors in the brain that sumatriptan is, that ergot medicines we're also playing around with. There's something in that particular family of receptors that definitely has a common role in migraine and cluster and all primary headache pathophysiology, but we don't quite know what it is. So yes, psychedelics are huge area of research now. I think it's going to be some years just because the populations are small. It's hard to get funding for these studies, but you could do it like I did and experiment on your own.

1:03:21I'm not advocating for it, but it can help people. It did not work for me.

1:03:25Jonathan Fields: Have you ever tried? I have not, which is in Boulder. That makes me the weirdo here, by the way. It is a town where there's a lot of psychedelic, both therapeutic and recreational. Recreational, it's a little bit of a weird place. If we zoom the lens out here a little bit, are you optimistic? Yeah. I mean, I'm optimistic in that I think scientists are finally paying some attention to it. I think the recent success of the CGRP medications, such as they are, have provided a signal to big pharma that there's money to be made here. And let's face it, in the mercenary world we live in, we need pharma to pay attention.

1:04:08And if they think they can make a buck, they'll try to do that. So I think that there is a certain momentum that's happening now on headache science. And I guess there's a part of me that's optimistic that the book itself will give us some permission to talk about it in ways that we haven't. And maybe expose some of these forces that have been kind of a drag on headache research and on headache sort of as it's distilled through the culture, that those will be exposed in a new way and that people can talk about it openly and honestly. Most people that I talk to seem most hopeful that people they know who don't have headaches will have something they can put in their hand and say, see, this is what I'm going through.

1:04:52I guess I'm hopeful that maybe that'll help too.

1:04:54Jonathan Fields: It feels like a good place for us to come full circle as well. So I always wrap with the same question here, which is in this container of Good Life Project, if I offer up the phrase to live a good life, what comes up? to live a good life to me is to have your health to have people around you who support you and are there for you whether you're healthy or not and to be in a world where we don't judge where we sort of stop judging each other and measuring our pain against one another and creating hierarchies of suffering. I think that to me is a good life. Thank you.

1:05:58Jonathan Fields: and Troy Young, Christopher Carter crafted our theme music. And of course, if you haven't already done so, please go ahead and follow Good Life Project in your favorite listening app or on YouTube too. If you found this conversation interesting or valuable and inspiring, chances are you did because you're still listening here. Do me a personal favor, a seven second favor, share it with just one person. I mean, if you want to share it with more, that's awesome too, but just one person even, then invite them to talk with you about what you both discovered to reconnect and explore ideas that really matter, because that's how we all come alive together.

1:06:34Jonathan Fields: Until next time, I'm Jonathan Fields, signing off for Good Life Project.

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