The Causes & Treatments for Autism | Dr. Karen Parker

1. 0:00 – 1:30

   Dr. Karen Parker

   1. AHAndrew Huberman0:00

      Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Karen Parker. Dr. Karen Parker directs the Social Neurosciences Research Program at the Stanford University School of Medicine. The goal of her laboratory's research is to understand the biological basis of social functioning at every stage of the lifespan. So this includes the bonds that form between infant and parent or parents, as well as the bonds that occur between children as they grow up, which, of course, form the template for social functioning when we become adults. Dr. Parker's research is heavily focused on autism and indeed on all forms of autism spectrum disorders. Today, we discuss autism, we talk about the prominent theories and current understanding of the biological basis for autism, as well as what still remains mysterious and unresolved about the causes of autism. You may have heard that the incidents or perhaps just the diagnosis of autism has dramatically increased in the last 10 to 15 years, and today, we discuss why it is in fact that the incidents, not just the diagnoses but the incidents of autism has so dramatically increased. And perhaps most excitingly, Dr. Parker shares with us brand new research findings from her laboratory that point to a new understanding of what causes autism as well as a novel treatment for autism.

2. 1:30 – 6:25

   Sponsors: Eight Sleep, LMNT & Aero Press

   1. AHAndrew Huberman1:30

      Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep tracking capacity. I've spoken many times before on this podcast about the fact that sleep is the foundation of mental health, physical health, and performance. Now, a key component of getting a great night's sleep is that in order to fall and stay deeply asleep, your body temperature actually has to drop by about one to three degrees, and in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees. One of the best ways to make sure that those temperature changes occur at the appropriate times, at the beginning and throughout and at the end of your night when you wake up, is to control the temperature of your sleeping environment, and that's what Eight Sleep allows you to do. It allows you to program the temperature of your mattress and sleeping environment such that you fall and stay deeply asleep easily and wake up each morning feeling incredibly refreshed and energized. I've been sleeping on an Eight Sleep mattress cover for almost three years now, and it has dramatically improved the quality of my sleep, so much so that when I travel and I'm at a hotel or an Airbnb and I don't have access to my Eight Sleep, I very much look forward to getting home because my sleep is always better when I sleep on my Eight Sleep mattress cover. If you'd like to try Eight Sleep, you can go to eightsleep.com/huberman to get $150 off their Pod 3 mattress cover. Eight Sleep currently ships in the USA, Canada, UK, select countries in the EU, and Australia. Again, that's eightsleep.com/huberman. Today's episode is also brought to us by LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means zero sugar and the appropriate ratios of the electrolytes sodium, magnesium, and potassium. And that correct ratio of electrolytes is extremely important because every cell in your body, but especially your nerve cells, your neurons, relies on electrolytes in order to function properly. So when you're well-hydrated and you have the appropriate amount of electrolytes in your system, your mental functioning and your physical functioning is improved. I drink one packet of LMNT dissolved in about 16 to 32 ounces of water when I wake up in the morning, as well as while I exercise, and if I've sweat a lot during that exercise, I often will drink a third LMNT packet dissolved in about 32 ounces of water after I exercise. LMNT comes in a variety of different flavors, all of which I find really tasty. I like the citrus, I like the watermelon, I like the raspberry. Frankly, I can't pick just one. It also comes in chocolate and chocolate mint, which I find taste best if they are put into water dissolved and then heated up. I tend to do that in the winter months because, of course, you don't just need hydration on hot days and in the summer and spring months but also in the winter when the temperatures are cold and the environment tends to be dry. If you'd like to try LMNT, you can go to Drink LMNT, spelled L-M-N-T, .com/huberman to try a free sample pack. Again, that's drinklmnt.com/huberman. Today's episode is also brought to us by AeroPress. AeroPress is similar to a French press for making coffee but is in fact a much better way to make coffee. I first learned about AeroPress well over 10 years ago, and I've been using one ever since. AeroPress was developed by Alan Adler, who was an engineer at Stanford, and I knew of Alan because he had also built the so-called Aerobie Frisbee, which I believe at one time, perhaps still now, held the Guinness Book of World Records for furthest thrown object, and I used to see Alan, believe it or not, at parks around Palo Alto, testing out different Aerobie Frisbees, so he was sort of famous in our community for developing these different feats of engineering that turned into commercial products. Now, I love coffee. I'm somebody that drinks coffee nearly every day, usually about 90 to 120 minutes after I wake up in the morning, although not always. Sometimes if I'm going to exercise, I'll drink coffee first thing in the morning, but I love, love, love coffee, and what I've personally found is that by using the AeroPress, I can make the best possible tasting cup of coffee. I don't know what exactly it is in the AeroPress that allows the same beans to be prepared into a cup of coffee that tastes that much better as compared to any other form of brewing that coffee, even the traditional French press. The AeroPress is extremely easy to use, and it's extremely compact. In fact, I take it with me whenever I travel, and I use it on the road in hotels, even on planes. I'll just ask for some hot water, and I'll brew my coffee or tea right there on the plane. If you'd like to try AeroPress, you can go to aeropress.com/huberman. That's A-E-R-O-P-R-E-S-S .com/huberman to get 20% off any AeroPress coffee maker. AeroPress ships anywhere in the USA, Canada, and over 60 other countries around the world. Again, that's aeropress.com/huberman to get 20% off. And now for my discussion with Dr. Karen

3. 6:25 – 10:41

   Autism, Frequency, Diagnosis

   1. AHAndrew Huberman6:25

      Parker. Dr. Karen Parker, welcome.

   2. KPDr. Karen Parker6:28

      Thank you. It's great to be here.

   3. AHAndrew Huberman6:29

      This is going to be perhaps one of the longer conversations that we've been able to have over the years, um, in part because whenever I see you on campus, we're heading in our respective directions. But I'm very excited because the topic of autism is one that is on a lot of people's minds. And I think the first question that always comes up, it seems, is whether or not the frequency of autism is indeed increasing or whether or not the field of medicine is getting better at detecting what was always there over time. Do we have any clear answers to that?

   4. KPDr. Karen Parker7:05

      Well, I think it's a multifactorial answer. So we're getting better at detecting autism, right? So in the past, we were diagnosing kids at nine or 10 years of age, right? And now clinicians are able to reliably diagnose kids, um, at two to three years of age, right? So there's more people. Um, there are- pediatricians have autism screeners now, so when you bring in your baby and over the first couple years of life, you're filling out screeners that are looking for autism symptoms, right? So, so there's just a lot more awareness around autism. But the rates have increased to now one in 36 US children have a diagnosis of autism-

   5. AHAndrew Huberman7:45

      Wow.

   6. KPDr. Karen Parker7:45

      ... which is over two years ago, it was one in 44. So-

   7. AHAndrew Huberman7:49

      One in 36?

   8. KPDr. Karen Parker7:50

      Mm-hmm.

   9. AHAndrew Huberman7:51

      Wow, I feel like it was just yesterday when it was one in 80. But is one in 36, um, the average across boys and girls? Um, does it skew differently if you look at just male births versus female births?

   10. KPDr. Karen Parker8:07

       Yeah, that's a great question. So autism is male-biased in prevalence. So you have, and again, the studies vary. I mean, it's, it's worth noting that autism is a highly clinically heterogeneous disorder, which means that if you've met one kid with autism, you've met one kid with autism, right? So, so we have to bear that in mind as we have this conversation. But, you know, different studies show that about for every one girl, there's three to four boys that are impacted by autism. So there's, you know, differences in the prevalence rate and also there's different monitoring sites. So the way in the US that these data are generated is the CDC has 11 monitoring sites across the country. And so they, they follow, um, children and then that's where we, um, that's where the prevalence rates come from, and they release new prevalence rates every, you know, few years.

   11. AHAndrew Huberman8:57

       So if physicians are able to detect autism early, say, in a two-year-old or-

   12. KPDr. Karen Parker9:02

       Yeah.

   13. AHAndrew Huberman9:03

       ... a three-year-old, I have to imagine that they're working off of tests that don't rely heavily on language because even though you can get, you know, some verbose two and three-year-olds, most two and three-year-olds don't have a very extensive vocabulary. Um, and I'm guessing that they're also relying on things like visual gaze, um, among other things. Um, we've already made clear that this is, um, not a discussion to allow people to diagnose themselves or others, but, um, with that said, what are some of the diagnostic tools that people use? You know, um, is it language? Is it vision, or does it present as, um, you know, abnormal auditory processing? Maybe you could give us a sampling.

   14. KPDr. Karen Parker9:49

       So autism is, um, a behavioral diagnosis, right? So unlike other areas of medicine where you might be able to take a blood test or there's other sort of tools, it's all a behavioral diagnosis by, um, an expert, so usually, um, a psychiatrist or a psychologist. And they look for two core features. So the- so this is based on the DSM, um, 5, and the, er... the two core features are pervasive social interaction challenges and the presence of restricted repetitive behavior. But there are a lot of people with autism who have anxiety. There are a lot of people with sensory challenges. There are a lot of people with seizure disorders, um, sleep disorders. So again, it's each person with autism has this sort of unique collection of traits, and, you know, that's how they get diagnosed.

4. 10:41 – 13:00

   Early Interventions; Heritability & Autistic Traits

   1. KPDr. Karen Parker10:41

   2. AHAndrew Huberman10:41

      And we're going to talk a lot today about interventions, but how early are some of the behavioral interventions, and I should just say any interventions introduced nowadays? So if s- uh, someone brings their child to the pediatrician and they take one of these tests and that, uh, child is deemed as having autism, um, will the, will the one-year-old or the, you know, two-year-old immediately go into behavioral interventions?

   3. KPDr. Karen Parker11:06

      Well, so usually you need to have the diagnosis of autism and then there are behavioral interventions-

   4. AHAndrew Huberman11:10

      Mm-hmm.

   5. KPDr. Karen Parker11:10

      ... or a variety of different ones, um, that are used. There are some studies where, um, uh, because autism's highly heritable, you can have one child with autism and then you, y- if you have subsequent children, you're at an increased risk of having subsequent children with autism, and these are called baby sibling studies. So what you're doing is enriching the population of infants that you follow prospectively, um, who are more likely to receive an autism diagnosis. And there are studies where some of those children are enrolled in behavioral studies even when they're, quote unquote, at risk.

   6. AHAndrew Huberman11:46

      I've heard before that, you know, parents in which one or typically both parents are, say, of the engineering, mathy, physics, quote unquote, hard science type are, um, more likely to have autistic children. Is that true? I mean, did that bear out in the data? You know, if you look at profession or, or, um, you know, undergraduate major, uh, does any of that correlate with the probability of having an autistic child?

   7. KPDr. Karen Parker12:16

      Yeah, well, what I can say is that there's been some studies. So what we know is that autistic traits are continuously distributed across the general population. And there was a study and there's a couple different instruments that are used to be able to measure these autistic traits. So there's something called the social responsiveness scale, and then that's a US-based instrument, and there's an autism quotient that's a similar measure that was, um, designed in England. And what, what we know from work with the AQ is that individuals that are in intense STEM fields like engineering, physics, and math have a greater burden of autistic traits, even if they don't have an autism diagnosis.

   8. AHAndrew Huberman12:57

      Okay. So that leads me to wonder whether or

5. 13:00 – 21:29

   Autistic Spectrums; Studying Autism

   1. AHAndrew Huberman13:00

      not this whole business of a spectrum-

   2. KPDr. Karen Parker13:03

      Yeah.

   3. AHAndrew Huberman13:03

      ... is actually multiple spectra, spectrums. Is it spectrums or spectra? What?

   4. KPDr. Karen Parker13:10

      (laughs)

   5. AHAndrew Huberman13:10

      Someone will put it in the, in the comments on YouTube, we know that for sure.

   6. KPDr. Karen Parker13:13

      (laughs)

   7. AHAndrew Huberman13:13

      Please let me know. I would like to know. What is the plural of spectrum, spectrums? Um, you know, because when we hear the word spectrum, we think, "Okay, there's a spectrum of severity," right? And in fact, I have some experience with, um, severe autism, um, not in my family, but where I went to undergraduate university, uh, UC Santa Barbara, down the way from that school was the Devereux School, which was a school which, um, has been, uh, there for a long time, that, um, parents would send their kids if they were, quote unquote, severely autistic. It was actually where, um, Dustin Hoffman went to, um, study for his role in Rain Man.

   8. KPDr. Karen Parker13:49

      Yeah.

   9. AHAndrew Huberman13:50

      And the c- uh, the kids, who were really delightful, they used to come into town every once in a while to the coffee shop where I'd study, and they would also continue on from there to Kmart, which is why the Dustin Hoffman character would say, "Gotta go to Kmart. Gotta go to..." He would do that repetition.

   10. KPDr. Karen Parker14:03

       That's fascinating.

   11. AHAndrew Huberman14:03

       Right. That Kmart was down the road from-

   12. KPDr. Karen Parker14:04

       Huh.

   13. AHAndrew Huberman14:05

       ... our, you know, our college housing and the Devereux School. Those kids were literally in a, um, o- away-from-home facility full time.

   14. KPDr. Karen Parker14:14

       Hmm.

   15. AHAndrew Huberman14:14

       And I spoke to some of the parents at one point, and they were at that facility, meaning the parents had sent them a- their children away to live there-

   16. KPDr. Karen Parker14:22

       Yeah.

   17. AHAndrew Huberman14:22

       ... full time. Of course, they'd get visits and they'd get visits home, um, because they were, I suppose we could say at the far end of some spectrum that made it, at least to the parents' idea, impossible for them to be at home. Okay, now, at the other end of the spectrum, if one is just simply thinking in terms of severity, I know people who have self-identified as au- autistic.

   18. KPDr. Karen Parker14:45

       Mm-hmm.

   19. AHAndrew Huberman14:45

       That's how they refer to it, so I feel comfortable, um, saying that they've said, "I am autistic."

   20. KPDr. Karen Parker14:50

       Yeah.

   21. AHAndrew Huberman14:50

       Um, and they seem pretty high functioning, meaning they have driver's licenses, drive cars, are in healthy relationships, and manage life appa- uh, apparently well. Um, they have some traits that, yes, I would agree, are a little bit different.

   22. KPDr. Karen Parker15:06

       Mm-hmm.

   23. AHAndrew Huberman15:07

       Right? So this is where we get into neurodivergence.

   24. KPDr. Karen Parker15:09

       Right.

   25. AHAndrew Huberman15:09

       Um, but I guess the point is, you know, should we think about autism as on a spectrum or given the fact that there are these, um, kind of collections of different traits, could there be a spectrum of severity, also a spectrum of, um, you know, more s- uh, stereotype behaviors? Um, another spectrum that intersects with that that has to do with, you know, obsession with a particular topic. You know, you could imagine that there are, you know, 50 or 60 different spectra or spectrums.

   26. KPDr. Karen Parker15:35

       Yeah.

   27. AHAndrew Huberman15:35

       I still don't know which one to say.

   28. KPDr. Karen Parker15:36

       (laughs)

   29. AHAndrew Huberman15:36

       And that when we talk about the spectrum, we're really talking about something that's in multiple dimensions and not just one line that goes from severe to mild.

   30. KPDr. Karen Parker15:46

       Yeah.
6. 21:29 – 29:55

   Environment, Risk Factors & In Utero Development

   1. AHAndrew Huberman21:29

      So, you've been talking about the genetic influences on autism, and of course, genes in the environment interact-

   2. KPDr. Karen Parker21:34

      Right.

   3. AHAndrew Huberman21:34

      ... right? It's never nature or nurture. It's always an interaction, and that isn't just about the epigenome. It's also just about the fact that nature impacts the genome, and our genome impacts the way that we interact with the environment, et cetera. So, what is the role of the environment in autism, both the frequency and the presentation of autism?

   4. KPDr. Karen Parker21:51

      Right. So, I mean, there are, again, lots of different epidemiological studies. So, um, advanced parental age, uh, prematurity, severe prematurity is a risk factor for autism, um, maternal illness during pregnancy. Um, so there's, there's a bunch of different things that have been associated with an increased risk for autism.

   5. AHAndrew Huberman22:14

      In terms of environmental influences and how they can intersect with biology, um, one of the things that I was really struck by in the early 2000s that, at least by my read of the literature, hasn't really gone anywhere, was this idea that was proposed by Pasko Rakic-

   6. KPDr. Karen Parker22:28

      Mm-hmm.

   7. AHAndrew Huberman22:28

      ... who used to run the neurobiology department-

   8. KPDr. Karen Parker22:29

      Yes.

   9. AHAndrew Huberman22:30

      ... um, at Yale. Um, expert in brain neuroanatomy, in non-human primates, and in humans, embryology, um, really a luminary of our field, and he had a series of papers exploring how the migration of neurons during early development, you know, as you and I both know, but most people out there probably don't know 'cause we haven't covered this in the podcast, um, it's not typical dinner table conversation, you know, when yo- when an embryo, when a human embryo is developing, the, the neurons are born at one location and they migrate out some distance to their final, um, resting place where then they grow out their connections and connect with one another. And that process of neural, neuronal migration is oh-so critical for the eventual wiring of the brain. And Rakic had this idea that perhaps, and I really want to emphasize perhaps, that the more frequent incidents of autism might be correlated with the increase in early prenatal ultrasound. And he had these papers published in a number of really high profile journals, including Proceedings of the National Academy and Science and elsewhere showing that, in a mouse model, if you do ultrasound, w- with each successive ultrasound, you got more migration errors, right? So there's, to me, it was a, you know, an interesting example of, of the environment, frequency of ultrasound, and cell migration having some sort of interaction, but it seemed like it never went anywhere. It never got tacked to, okay, you should keep in mind the number of ultrasounds that you're getting for your child. And of course, ultrasounds are critical for pe- for pregnant women to get, um, because they can stave off a number of developmental issues and they're super important, but, you know, we've heard about ultrasound, you know, within the scientific literature, and then occasionally we'll hear other theories about, okay, it's having two parents who are both engineers, and then we'll hear, "Oh, you know, it's, um, you know, toxicity in the food environment." We've heard, you know, hypotheses about vaccines or the, the adjuvants that the vaccines are contained in. You know, in that large cloud of theories, has anything really, um, emerged from them as like, okay, there really seems to be at least one major risk factor, environmental risk factor? Because I feel like all those theories kind of come up, get some popular press, a bunch of papers are published, sometimes those papers are retracted, like in the case of the vaccines-

   10. KPDr. Karen Parker24:47

       Right. (laughs)

   11. AHAndrew Huberman24:47

       ... um, and then the theory kind of dies.

   12. KPDr. Karen Parker24:50

       Yeah.

   13. AHAndrew Huberman24:51

       So, is there any specific environmental influence on autism that we can say, "Yes, there really seems to be something there"?

   14. KPDr. Karen Parker24:59

       Yeah. I, I mean, it's a, it's a really spectacularly good question. I think the tricky part about it is that...... every single person that comes into a trial has a different genetic background, right? And so until we can have these a priori stratified trials where you could then, you know, as a good scientist, you would only manipulate maybe one, two variables at a time, right? But when you're doing these large epidemiological studies, because you can't, it's very difficult to do experimental studies, right? Especially with developing children. Um, I think that's an incredibly difficult study to do, right? So there's been an interest in this field of there's these neurogenetic syndromes that have high penetrance for autism, which basically means that you could have a disorder, um, or, you know, another genetic condition, let's say, it doesn't have to be a single gene, but that a lot of those kids tend to also get an autism diagnosis. And so there's been work in like, so for instance, Fragile X is a good example, where because autism is so diverse in terms of clinical presentation that let's say you have a medication that could work for a handful of kids in the trial, you may not be statistically powered to see it, right? So, so, you know, the way I think about the autism world is there's so little we don't know. So think about being in a dark room and you have a flashlight, and you only see where you shine the light, right? And so if you think about a very heterogeneous, genetically heterogeneous study, it, it's going to be very difficult to tease out these pieces because an environmental risk factor, um, might be a driver for one kid but not another, right? And so I think what we need to do is to have these genetically defined subgroups of individuals and then be able to test the G by, gene by environment interactions or in this genetically defined group of individuals, um, can we test this certain medication to see if it's beneficial for this subgroup of children?

   15. AHAndrew Huberman26:58

       Got it. So you, you mentioned Fragile X-

   16. KPDr. Karen Parker27:00

       Yeah.

   17. AHAndrew Huberman27:00

       ... which, um, we know, um, presents with autism-like symptoms in some cases. And then I think of another disease like, um, TIMOTHY syndrome.

   18. KPDr. Karen Parker27:09

       Uh-huh.

   19. AHAndrew Huberman27:10

       A mutation in an L-type calcium channel, which, um, for those of you that don't know what these L-type calcium channels are, they're, they're not just important for the function of neurons in the brain. They're really important for the function of neurons and other, other tissues, including heart tissue, right? So, um, kids with TIMOTHY syndrome have cardiac issues-

   20. KPDr. Karen Parker27:28

       Yeah.

   21. AHAndrew Huberman27:29

       ... and they have autism. So, you know, I think it's important for us to kind of explore this a bit because in most people's minds, you know, kids with autism have autism, and occasionally they'll have other issues, you know, gut issues or heart issues or, um, musculoskeletal issues, but we often think that that's the consequence of the autism, but oftentimes they, they have multiple things going on-

   22. KPDr. Karen Parker27:50

       Right.

   23. AHAndrew Huberman27:51

       ... and the autism actually could be secondary or independent of the other thing that's going on. So this is what leads me back to the, this idea of, of a spectrum.

   24. KPDr. Karen Parker27:59

       Mm-hmm.

   25. AHAndrew Huberman27:59

       You know, is, you know, is it possible that what we call autism is actually like 50 different d- disorders or 50 different conditions depending on what one wants to call them? Um, I mean, what is autism really? I mean, is it, it's... What does it really center around? Like d- d... And I think here maybe it's useful to go, like, do we go to the diagnostic criteria? Like how do we decide if a child has autism if they also have a bunch of other things-

   26. KPDr. Karen Parker28:26

       Right.

   27. AHAndrew Huberman28:26

       ... that, that are challenging them?

   28. KPDr. Karen Parker28:27

       I mean, I th- I think that that's the $64,000 question, right? And, and, and again, in other areas of medicine, so if you think about, let's think about cancer biology, right? Like decades ago, somebody would come in with cancer and you would hit them with radiation chemotherapy, and that was the best that we could do, right? But with the invention of a lot of molecular tools, you can remove a, a tumor and you can do molecular profiling and even, you know, have personalized medications made, right, to attack that t- tumor. And so, you know, what's really tricky when you have a behavioral diagnosis that's not biologically defined, you, you see a lot of heterogeneity. So it's incredibly difficult, I think, to answer this question because we don't know how many kinds of autisms there are, right? Like there will be people who say if you have a disorder like Fragile X or Prader-Willi syndrome or TIMOTHY syndrome or, or a variety of these other conditions, there will be people, people s- I, I've heard clinicians say, "Well, that's not really autism, right? That's a piece of Fragile X, right?" But if it's a behavioral diagnosis and they meet b- behavioral criteria, it becomes this weird circular argument, right? So like until we really understand what autism is, I, I, I think that it's going to be very tricky to start, you know, sub-defining different aspects of the condition.

7. 29:55 – 31:26

   Sponsor: AG1

   1. KPDr. Karen Parker29:55

   2. AHAndrew Huberman29:55

      As we all know, quality nutrition influences of course our physical health, but also our mental health and our cognitive functioning, our memory, our ability to learn new things and to focus. And we know that one of the most important features of high quality nutrition is making sure that we get enough vitamins and minerals from high quality unprocessed or minimally processed sources, as well as enough probiotics and prebiotics and fiber to support basically all the cellular functions in our body, including the gut microbiome. Now, I, like most everybody, try to get optimal nutrition from whole foods, ideally mostly from minimally processed or non-processed foods. However, one of the challenges that I and so many other people face is getting enough servings of high quality fruits and vegetables per day, as well as fiber and probiotics that often accompany those fruits and vegetables. That's why way back in 2012, long before I ever had a podcast, I started drinking AG1. And so I'm delighted that AG1 is sponsoring the Huberman Lab Podcast. The reason I started taking AG1 and the reason I still drink AG1 once or twice a day is that it provides all of my foundational nutritional needs. That is, it provides insurance that I get the proper amounts of those vitamins, minerals, probiotics and fiber to ensure optimal mental health, physical health, and performance. If you'd like to try AG1, you can go to drinkag1.com/huberman to claim a special offer. They're giving away five free travel packs plus a year supply of vitamin D3 K2. Again, that's drinkag1.com/huberman to claim that special offer.

8. 31:26 – 43:24

   Oxytocin, Vasopressin, Social Behavior & Parent-Child Bonding

   1. AHAndrew Huberman31:26

      Well, this is probably a good time for us to think about the work that you've done in terms of trying to tack-...the biology of social communication, uh, and behavior-

   2. KPDr. Karen Parker31:40

      Yeah.

   3. AHAndrew Huberman31:40

      ...right? Those things interact, not just language, but also behavior, to autism in humans using non-human primate models, and then, of course, to also discuss some of the work that you've been doing in humans. And we can't have that discussion without first having a discussion about two neuropeptides that I think most people have heard of at least one of them, and I think there's a lot of misunderstanding about, but you're going to clarify that for us, which are oxytocin and vasopressin. So before we dive into the, uh, the important work that you've been doing on vasopressin in particular, but also oxytocin and autism, what are oxytocin and vasopressin really?

   4. KPDr. Karen Parker32:22

      Okay. So they are these small little peptide, they're nine amino acids long, so very tiny. They only differ by two amino acids, and they're these ancient peptides that are hundreds of millions of years old. And in almost any species studied, um, whether it's the current version you might have vasotocin or other mesotocin, which are, um, sort of precursor forms in other species, but they're highly evolutionarily conserved, and they're involved in social behavior, um, in pretty much any, it could be egg laying, it could be, you know, but, but reproduction and social behavior across the phylogenetic taxes actually.

   5. AHAndrew Huberman32:59

      So house cats make vasopressin and oxytocin. Humans obviously make vasopressin-

   6. KPDr. Karen Parker33:04

      Yes.

   7. AHAndrew Huberman33:04

      ...and oxytocin, and pretty much every other species that has to interact with and connect with other-

   8. KPDr. Karen Parker33:10

      Yes.

   9. AHAndrew Huberman33:10

      ...members of its species.

   10. KPDr. Karen Parker33:11

       Especially mammals, right? So oxytocin and vasopressin are pervasive in mammalian species.

   11. AHAndrew Huberman33:16

       Mm-hmm. Do the different species tend to make oxytocin and vasopressin in similar brain areas and tissues?

   12. KPDr. Karen Parker33:26

       Um, yes, but not completely overlapping. But I, I think the thing that, the, the beautiful mystery about these, a- and the infuriating piece of them, is that because they're so structurally similar, um, they can have similar effects, and they, there's four receptors that they bind to. So if you think about a hormone or a neurotransmitter, so oxytocin, vasopressin, if you think about them like a key, and a receptor like a lock, and you have to put them together to open a door, open behavior, they can bind to these four receptors. So it can be very difficult to disentangle which one is acting and at which receptor and where in the brain.

   13. AHAndrew Huberman34:05

       Oh, so oxytocin and vasopressin are chemically similar?

   14. KPDr. Karen Parker34:07

       Yes.

   15. AHAndrew Huberman34:08

       Interesting.

   16. KPDr. Karen Parker34:09

       Yes.

   17. AHAndrew Huberman34:09

       And, uh, where would you say lies their greatest, um, output divergence, which is just nerd speak for... Um, is there an example of something that oxytocin does that vasopressin doesn't and vice versa?

   18. KPDr. Karen Parker34:20

       Yeah. Okay. So what's really fascinating is these two neurotransmitters or hormones were discovered for their peripheral effects, which basically means not in their brain, but somewhere in their body. And so oxytocin's involved in, um, uterine contractions and milk letdown, and so was during lactation. So people sort of always thought of it as the female hormone. And then vasopressin has, um, at least in the, in the peripheral system, has been involved in, um, urine regula- like urinary output regulation, blood pressure. Um, and so we only knew about their, their physiological roles as they were sort of classic hormones for decades. And what was interesting is these, um, like naming conventions are fascinating in medicine, right? So you could name a virus after where it was first found, right? Or it could be named after somebody who discovered the disease, like Alzheimer's for instance is a good example. And what was interesting, oxytocin was only named once. Vasopressin was named twice. So it's either called arginine vasopressin or antidiuretic hormone. And so it had two different names, and so as you can imagine, sometimes genes are named twice, and so somebody in cancer is studying one gene and somebody in autism is studying another, and they're not even communicating because they don't even realize that they've, at least historically, now we have all kinds of gene annotation sites, so it's less likely to happen now, but... But what was fascinating is they were, these hormones were named, oxytocin is Greek for quick birth. So for decades, people only appreciated their physiological roles. But, but there are neuroanatomists saying, "Hey, so these are both made..." They're made in a lot of different places, but the, the, the action sort of happens in the hypothalamus where they're made. And there were anatomists that said, "Wait, these sort of project back into the brain. What are these doing in the brain?" And one of my favorite historical stories was, um, I had a mentor, um, a, a colleague, like a, you know, who I didn't train with, but he was, um, s- a real source of wisdom to me for many years, and his name's Cort Peterson, and he told me this wonderful story about this Duke zoologist named Peter Klopfer. And, um, Peter was studying ungulates, so sheep and goats, and he wrote a story, a paper in 1971 called Mother Love: What Turns It On. And, um, you know, one thing about science is I love going back and seeing where do the pearls of wisdom come from? And so he wrote this and said, "You know, oxytocin is orchestrating all these events of motherhood, and there are sheep and goats in particular that have offspring that are precocious, meaning they're basically born ready, you know, within an hour they can run with the herd, unlike our species which is altricial, meaning we have very helpless infants. And Mom needs to bond really quickly with that baby if it's going to be running around and you only, you know, uh, from an evolutionary perspective, you want to be investing in the baby that's yours, not somebody else's, right?" And, um, he hypothesized that it was oxytocin that was being co-released into the brain and during milk letdown that was what turned mother love on. And that was really the beginning of this whole field of thinking, and so that opened up thinking about oxytocin in rodent maternal care and a variety of other instances.

   19. AHAndrew Huberman37:38

       Can I just briefly, uh, interrupt you 'cause I find this so interesting and I know it's interesting to, uh, everyone listening as well because, you know, w-Yes, uh, and thank you for, um, making it clear that oxytocin has many different roles.

   20. KPDr. Karen Parker37:50

       Yeah.

   21. AHAndrew Huberman37:51

       Um, but this role of mother love and-

   22. KPDr. Karen Parker37:53

       Yep.

   23. AHAndrew Huberman37:53

       ... bonding to infant, um, has me needing to ask whether or not the idea was that oxytocin is released in the mother when she interacts with her own baby, um, and that leads me to the question, is oxytocin also released in the baby, um, in reaction to, to the mother, and how long is that effect lasting? Because in order to have a pervasive bond with that baby and not just some other baby, and of course, we still have visual cues and, you know-

   24. KPDr. Karen Parker38:20

       Yeah.

   25. AHAndrew Huberman38:20

       ... we know our baby versus another baby, he- in most instances. Um, there are rare exceptions, uh, or perhaps not so rare exceptions, but leaving those aside, you know, y-... the mechanism that would allow for mother-infant bonding and infant-mother bonding by way of oxytocin presumably is something that is literally changing their brains.

   26. KPDr. Karen Parker38:40

       Yeah.

   27. AHAndrew Huberman38:40

       Saying i- it's y- you are the, are the center of my life.

   28. KPDr. Karen Parker38:44

       Yeah.

   29. AHAndrew Huberman38:44

       Right? And the baby, of course, is saying, "Well, you are my life-"

   30. KPDr. Karen Parker38:47

       Uh-huh.
9. 43:24 – 54:14

   Oxytocin in Humans; Social Features of Autism, Intranasal Oxytocin

   1. KPDr. Karen Parker43:24

   2. AHAndrew Huberman43:24

      In terms of when and how oxytocin is released, uh, you mentioned, um, mother-infant bonding. Um, I think you said, yes, that the infant is also releasing oxytocin, we think. Um, so it's, it's bidirectional. Um-

   3. KPDr. Karen Parker43:40

      W- we think. I think most of the work has been done in mom, would be... And, and again, this has not been really done well in primates, right? So we're extrapolating this information from species that have different evolutionary histories than us, right? So it's goats, sheeps, um-... prairie voles, mice, rats.

   4. AHAndrew Huberman44:00

      Mm-hmm. So what do we know about the role of oxytocin in humans? Do we, I mean, we know it's there.

   5. KPDr. Karen Parker44:05

      Yeah.

   6. AHAndrew Huberman44:06

      We presume, based on the animal models, that it's involved in mother-infant bonding, um, and presumably romantic partner bonding. At least you hear that-

   7. KPDr. Karen Parker44:16

      Yeah.

   8. AHAndrew Huberman44:16

      ... a lot. Um, it was unfortunately nicknamed the love hormone.

   9. KPDr. Karen Parker44:20

      Yes.

   10. AHAndrew Huberman44:20

       Um, and the reason it's unfortunate it was is that while that might cue attention to oxytocin, and I'm, you know, a big fan of people paying attention to biological phenomena, it, uh, it discards the other and many roles of, of oxytocin. But yeah, what can we say about oxytocin in humans if, if anything? Like do we know that it does an- I mean is it, we're just, so we're assuming based on the animal models that it does something.

   11. KPDr. Karen Parker44:43

       Yeah.

   12. AHAndrew Huberman44:43

       I mean, this is very different than like dopamine where there's tons of animal model data, but we know.

   13. KPDr. Karen Parker44:48

       Right.

   14. AHAndrew Huberman44:48

       But there are brain imaging where we know where dopamine is expressed-

   15. KPDr. Karen Parker44:51

       Yeah.

   16. AHAndrew Huberman44:51

       ... and do we even know where oxytocin receptors are expressed in the human brain? Presumably that information is, is out there.

   17. KPDr. Karen Parker44:57

       R- recently, but again, there's a lot of specificity, and I think if you're thinking about disorders, you would then have to study those specific subpopulations, right? And, and you need, you know, a lot of this work has been done, so you have to think about how do we study it, right? So the best way to study it would be to have radio tracers where you could then, which we do have for dopamine and, and other compounds, where you would then go and see where after somebody's performed a task do we see, you know, um, activation, right, or uptake. Um, there are some imaging studies, they're usually done giving intranasal oxytocin, um, and then you basically ask questions about, okay, we give you oxytocin intranasally, which presumably enters the brain. There's, we could talk about reasons why we think that. Um, and then we have you perform on some task, right? And so, you know, there's evidence if you give oxytocin, it diminishes the amygdala's response, um, to fearful stimuli, right? So that it might have this sort of pro-social effect, and, and it was actually data like that that caused people to start thinking, um, initially about oxytocin.

   18. AHAndrew Huberman46:00

       And those are data in humans. That's right, it reminds me that there was this brief moment where oxytocin wasn't just being discussed as the love hormone, it was, it was being discussed as the trust hormone.

   19. KPDr. Karen Parker46:10

       Correct.

   20. AHAndrew Huberman46:11

       Right? Also, um, far too simple a heuristic, but, but again, I think it's cool that the, you know, that the, the press picks up on these things and at least tells people about what's being discovered.

   21. KPDr. Karen Parker46:22

       Yeah.

   22. AHAndrew Huberman46:22

       And we just always have to be careful to not, um, uh, have it lead to the assumption that that's the only role of a given...

   23. KPDr. Karen Parker46:28

       Right.

   24. AHAndrew Huberman46:28

       ... of a given hormone. So, um, it can reduce, apparently it can reduce the output of the amygdala in some way.

   25. KPDr. Karen Parker46:35

       Mm-hmm.

   26. AHAndrew Huberman46:35

       This brain area, uh, associated with, um, threat detection, um, and so you could imagine how that would bias the person toward being more pro-social.

   27. KPDr. Karen Parker46:44

       Right.

   28. AHAndrew Huberman46:45

       Um, have there been studies exploring the role of oxytocin in making autistic children more pro-social? And behind that question, I suppose is the assumption you can verify or, or not, that autistic children are less pro-social than other children. Um, is that true? Um, or is it that, you know, autistic kids are just maybe more pro-social with the one friend they really, really like?

   29. KPDr. Karen Parker47:10

       Yeah.

   30. AHAndrew Huberman47:10

       Um, I happen to know some kids, uh, with autism or however you want to phrase it, and, um, they have close friends, and they seem to really like those specific friends a lot.
10. 54:14 – 55:16

    Sponsor: InsideTracker

    1. KPDr. Karen Parker54:15

    2. AHAndrew Huberman54:15

       I'd like to take a quick break and thank our sponsor, InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. Now, I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term health can only be analyzed from a quality blood test. A major problem with a lot of blood tests out there, however, is that you get information back about metabolic factors, lipids and hormones and so forth, but you don't know what to do with that information. With InsideTracker, they make it very easy because they have a personalized platform that allows you to see the levels of all those things, metabolic factors, lipids, hormones, et cetera, but it gives you specific directives that you can follow that relate to nutrition, behavioral modifications, supplements, et cetera, that can help you bring those numbers into the ranges that are optimal for you. If you'd like to try InsideTracker, you can go to insidetracker.com/huberman to get 20% off any of InsideTracker's plans. Again, that's insidetracker.com/huberman.

11. 55:16 – 1:06:30

    Oxytocin & Autism; Benefit & Risks

    1. AHAndrew Huberman55:16

       Is it known whether or not people with autism, assuming they meet the criteria for being autistic at that, at that moment, um, have lower natural circulating or active levels of oxytocin? Because that, you know, it's one thing for a nasal spray to, um, of oxytocin to improve social functioning. It's another, um, to know that it, that the effect is addressing an underlying biological deficit.

    2. KPDr. Karen Parker55:44

       Yeah. That's, it's such a great question. Okay. So we should unpack that 'cause there's been a lot of work in this area. So the first question is, where are we measuring the oxytocin, right? So we mentioned oxytocin has all kinds of effects in the body as well as the brain, and it's released into the blood, but it's also released directly into the brain, and there's variable evidence about if you measure it in blood, is it a readout of the brain or not, right, or should you be looking at something like spinal fluid that's maybe a, a better biochemical proxy of the brain? Um, most studies, so what I will say is there were, th- there's been m- a handful of small studies where there has been-... some, you know, there's been some benefit, maybe no benefit, small effects. We did a study that was a small study at Stanford, and it was based on, um, mouse genetic data. And I'll, I'll sort of walk you through what we did. Um, so there's multiple mouse models of these neurogenic syndromes where, um, people have social impairment, right? We can quib- quibble about whether that's autism or not, but that they have social impairment. And so that there are this, um, fragile X mouse, there's a Prader-Willi syndrome mouse, which is the MAGIL2 gene that, um, gets manipulated, and then there's a CATNAP2 mouse. And in all of those instances when you genetically modify those mice, you see a reduction of oxytocin in the hypothalamus. And what's interesting is that, um, in those instances where you see this genetic modification, you do see lower blood levels in these genetically defined models. What's really cool is you can give oxytocin across development in those models, and at least in the CATNAP2 mouse, you can restore oxytocin neuron number to equivalent of control animals, suggesting that oxytocin is doing something in these oxytocin-deficient animals, right? So these are not an oxytocin gene manipulation, but these are these syndromes where you see as a consequence of manipulating genes for these syndromes that oxytocin gets knocked down, right? And so our thinking when we went into our clinical trial was what if, um, it's blood oxytocin levels, that there are going to be a subset of individuals that just make less oxytocin.

    3. AHAndrew Huberman57:59

       Humans.

    4. KPDr. Karen Parker58:00

       Humans. And that maybe those are the individuals who could, who stand to benefit the most from treatment.

    5. AHAndrew Huberman58:05

       Mm-hmm.

    6. KPDr. Karen Parker58:06

       And so we were the first group, um, to ask, you know, across this range of individuals who showed up, and we did, in, in all the trials that we'll talk about today, um, these are done with my colleague Antonio Hardan at Stanford who's a child psychiatrist. Um, and we always have double blind, meaning that the investigative team is blind and that the, um, or unaware I should say, they're unaware of treatment and then the families and the children are unaware. Um, and then they're randomized, meaning there was an equal chance you could get either drug or placebo, um, and they're, and they're controlled, right? Okay, so we asked if we know what your pret- pretreatment, pretreatment blood oxytocin level is, who's gonna benefit from treatment? And we found a couple really interesting things. One was that the lower your baseline ox- so your pretreatment blood oxytocin level, you showed much greater benefit from the oxytocin intervention. These are chi-

    7. AHAndrew Huberman58:59

       One, one, uh, intervention, one nasal spray?

    8. KPDr. Karen Parker59:01

       This was four weeks. Sorry, I should have clarified.

    9. AHAndrew Huberman59:03

       Okay.

    10. KPDr. Karen Parker59:03

        This is four weeks of treatment being, um, administered oxytocl- tocin twice a day.

    11. AHAndrew Huberman59:08

        Okay.

    12. KPDr. Karen Parker59:09

        And, um, and, and so we saw effectiveness there.

    13. AHAndrew Huberman59:12

        May I, sorry to interrupt so much-

    14. KPDr. Karen Parker59:13

        Yeah.

    15. AHAndrew Huberman59:13

        ... but just, uh, males, male and female subjects?

    16. KPDr. Karen Parker59:16

        We did, but again, you know, because th- autism is male biased in prevalence, e- even if you make this heroic effort to over-recruit, try to get more girls in, um, in, in the study we usually try to aim for the prevalence rate because it's difficult to get girls just 'cause there's fewer of them.

    17. AHAndrew Huberman59:31

        Got it. Okay, but, um, boys and girls were included.

    18. KPDr. Karen Parker59:34

        Correct.

    19. AHAndrew Huberman59:34

        They're taking oxytocin over the period of, of-

    20. KPDr. Karen Parker59:37

        Four weeks.

    21. AHAndrew Huberman59:38

        ... several, four weeks. And if they started off with lower baseline levels of oxytocin, you observed a benefit of the oxytocin treatment-

    22. KPDr. Karen Parker59:45

        Yes.

    23. AHAndrew Huberman59:45

        ... in those individuals.

    24. KPDr. Karen Parker59:46

        Right.

    25. AHAndrew Huberman59:46

        What about the individuals who had normal to, to high levels?

    26. KPDr. Karen Parker59:49

        We, you didn't see much benefit, right? And so that was a s- a cue to me to think that there may be a subset of individuals that, you know, for whatever reason, they have lower oxytocin and that they may stand to benefit more from treatment. And none of the prior studies had looked at blood oxytocin levels, and so what we had thought was that, well, maybe if everybody had measured baseline blood oxytocin levels, maybe some of these, you know, maybe there would have been more, um, positive outcomes. So but there's a, there's a lot of controversy in this field about whether oxytocin is a treatment for autism, right? So after we completed that trial, there was a large multi-site, um, what's called a phase III oxytocin treatment trial that was done at, I think, five sites. And they gave oxytocin for an extended period of time, um, and they showed no benefit. Um, and, and-

    27. AHAndrew Huberman1:00:44

        Were they looking to see who started off with low levels of oxytocin at pretreatment?

    28. KPDr. Karen Parker1:00:49

        So what was interesting about that study, um, and there were a lot of issues with it, was that, um, e- oxytocin is something where you have to, i- i- if you look at it, it degrades. It's like that's kind of what I joke about, right? So you need to take it. We take ... When we go in, we have, like, these really intense protocols, right? So you go in and we have Vacutainer tubes that are cold, and we put them on ice and then the phlebotomist takes the blood from the child that we-

    29. AHAndrew Huberman1:01:17

        So a lot of technical-

    30. KPDr. Karen Parker1:01:18

        Right.
12. 1:06:30 – 1:14:30

    Neuroplasticity & Autism; Early Intervention; Challenges of Early Diagnosis

    1. KPDr. Karen Parker1:06:30

    2. AHAndrew Huberman1:06:30

       Um, I, I just want to ask because it feels relevant in a m- in a real way. Um, you know, if ultimately the goal of improving symptom profiles in autistic kids is about improving social cognition and social behavior, and that process involves rewiring of brain circuits, neuroplasticity, is there any reason to think that other approaches to inducing neuroplasticity would be beneficial, even if they're not in the biological pathways that are disrupted in autism? Um, I think, for instance, about the now extensive use of SSRIs-

    3. KPDr. Karen Parker1:07:09

       Mm-hmm.

    4. AHAndrew Huberman1:07:09

       ... for the treatment of depression. In some cases it works, in some cases it doesn't. Side effect profiles are a serious concern-

    5. KPDr. Karen Parker1:07:16

       Yeah.

    6. AHAndrew Huberman1:07:16

       ... as, uh, we discussed on this podcast before. But ultimately, we know that depression is not a serotonin deficiency. In most cases, SSRIs or atypical antidepressants like bupropion, Wellbutrin, and things of that sort, when they work, they probably work because of their ability to induce neuro- or assist neuroplasticity.

    7. KPDr. Karen Parker1:07:35

       Right.

    8. AHAndrew Huberman1:07:36

       Right. Um, also, the trials on psilocybin are not really about psilocybin. They're about neuroplasticity.

    9. KPDr. Karen Parker1:07:43

       Right.

    10. AHAndrew Huberman1:07:43

        At least the trials for depression, right? There may be other uses of psilocybin-

    11. KPDr. Karen Parker1:07:47

        Yeah.

    12. AHAndrew Huberman1:07:47

        ... that relate more directly to the effects of psilocybin. But ultimately, you know, what we're talking about here is the, the attempt to rewire the brain in a specific way, whether or not it's a- assisted by oxytocin or some other mechanism. So the question is, are there trials happening where people are exploring, say, psilocybin, MDMA, which, by the way, we know, um, increases oxytocin-

    13. KPDr. Karen Parker1:08:10

        I was going to mention that.

    14. AHAndrew Huberman1:08:11

        ... and serotonin dramatically-

    15. KPDr. Karen Parker1:08:12

        Yes, yes.

    16. AHAndrew Huberman1:08:13

        ... as well as, um, things like atypical antidepressants?...in kids that have autism, not because we think that those, uh, autistic kids are deficient in any of the neurochemicals that these drugs would target, but that these drugs can help rewire the brain, and ultimately, that's what these kids need.

    17. KPDr. Karen Parker1:08:29

        Right. I, I, it's a really great point, and I, there might be subsets of kids, right? There might be kids where there would be a medication that would target other pathways, but that potently releases oxytocin, right? That, um, but there might be kids that have an oxytocin deficiency, right? But I think that that circles back to your point at the beginning, or our point, is that autism is a very heterogeneous condition, and being able to know before you begin a trial, right, like, "Who am I going to put into it? And what is my primary outcome?" Like, one measure that I think is going to move the needle, right? Like, it kind of requires a crystal ball. So there's a lot of guesswork that goes into this. Um, but I would v- very much like to see... I, I will say one other thing that, um, that I, I have a colleague named Adam Guastella who's at the University of Sydney, and he published a paper a year or two ago now suggesting that oxytocin be- may be most effective in kids at younger ages.

    18. AHAndrew Huberman1:09:26

        Hmm.

    19. KPDr. Karen Parker1:09:26

        And I, I, don't quote me, somewhere between two and, uh, you know, two and five, or three and six, or something like that.

    20. AHAndrew Huberman1:09:31

        We'll find the paper and put it in the show-

    21. KPDr. Karen Parker1:09:33

        Yeah.

    22. AHAndrew Huberman1:09:33

        ... show notes.

    23. KPDr. Karen Parker1:09:33

        But, you know, and so it could be, to your point about neuroplasticity, that oxytocin may be maximally beneficial in younger ages, right? And if your, if these studies are these hodgepodges across ages and across sort of different social phenotypes, finding that signal is really important, right? And, and maybe age is a driver or, or maybe, you know, m- low blood oxytocin regardless of what age you are, or maybe in Adam's case, if you recruit really young children, you're likely to see a benefit just because the blain- the brain is wiring up and it's more plastic at, you know, younger ages.

    24. AHAndrew Huberman1:10:14

        Yeah, that's also a vote, um, in my opinion, um, for early, uh, examination of kids.

    25. KPDr. Karen Parker1:10:21

        Right.

    26. AHAndrew Huberman1:10:21

        Right? Like, parents really need to get autism screening, and perhaps maybe the most important thing is to make autism screening as available and as inexpensive as possible-

    27. KPDr. Karen Parker1:10:30

        Right.

    28. AHAndrew Huberman1:10:30

        ... for everyone, because of the importance of early intervention, even if it's purely behavioral intervention-

    29. KPDr. Karen Parker1:10:35

        Right.

    30. AHAndrew Huberman1:10:35

        ... but certainly if it's behavioral and drug intervention.
13. 1:14:30 – 1:17:05

    MDMA & Autism

    1. AHAndrew Huberman1:14:30

       there human trials f- exploring MDMA, uh, methylenedioxy-methamphetamine, also referred to as ecstasy, um, and/or psilocybin for, um, treatment of autism?

    2. KPDr. Karen Parker1:14:42

       So, I was aware that MAPS had an MDMA trial in autism. Um, I don't know what's happened with that.

    3. AHAndrew Huberman1:14:50

       Hmm. Yeah, perhaps it's still ongoing. I'll check the MAPS site. I'm in communication with them from time to time. I mean, the- the- the reason for asking, and of course, you know, but maybe in case, um, li- some of the listeners, um, don't, is that MDMA causes these massive increases in serotonin. That seems to be the major source of the MDMA effect, so to speak, um, based on the- our- work of our colleague, uh, Rob Malenka, and, um, in at least one human study comparing, um, MDMA to very high dose oxytocin treatment kind of ruled out the oxytocin spike that's induced by MDMA as the- as the source or the only source, but of course, these chemicals can synergize. I mean, but based on its chemical profile, oxytocin release, massive serotonin release, dopamine release, and a propensity to enhance neuroplasticity, I mean, assuming all the safety protocols were- were there, um, it seems like not the perfect drug, but not a bad choice, um, if, of course, it's inducing the kind of plasticity that someone with autism would be seeking.

    4. KPDr. Karen Parker1:15:52

       Right. I mean, I think the tricky part, especially in children, right, is there's gonna be a reluctance to potentially give them psychedelics, right? And so, you know, is there a way to modify, um, you know, the chemical compound to, you know, be something that parents might be more willing to give to their children, right?

    5. AHAndrew Huberman1:16:11

       Mm-hmm. Right, and I totally agree with that, um, I guess to play devil's advocate.

    6. KPDr. Karen Parker1:16:14

       Yeah.

    7. AHAndrew Huberman1:16:14

       Not against you, but, um-

    8. KPDr. Karen Parker1:16:16

       Yeah.

    9. AHAndrew Huberman1:16:16

       Uh, well, I'll just state it very directly-

    10. KPDr. Karen Parker1:16:18

        Yeah.

    11. AHAndrew Huberman1:16:18

        ... and then I'll- I'll take the heat as necessary. (laughs)

    12. KPDr. Karen Parker1:16:20

        (laughs)

    13. AHAndrew Huberman1:16:21

        Um, I mean, I've done two episodes about the, uh, the drugs that, you know, millions, tens of millions if not hundreds of millions of parents are already giving their kids for ADHD, which are, um, include amphetamines-

    14. KPDr. Karen Parker1:16:35

        Right.

    15. AHAndrew Huberman1:16:35

        ... including dioxin. Methamphetamine is actually a prescription drug-

    16. KPDr. Karen Parker1:16:38

        Right.

    17. AHAndrew Huberman1:16:38

        ... for a very small subset of kids with ADHD, but things like Adderall, Vyvanse, even methylphenidate, Ritalin, I mean, these are amphetamines. They induce dopamine release and norepinephrine release. And, uh, again, I'm not suggesting people, um, give their kids MDMA, um, to try and ameliorate symptoms of autism, but something chemically similar to it ought to be developed or at least explored in a human trial, in my- in my opinion. Well, time will tell. I'll reach out to the MAPS group and see- see what's happening.

14. 1:17:05 – 1:27:07

    Vasopressin, Social Interaction; Voles & Parenthood

    1. AHAndrew Huberman1:17:05

       Let's talk about vasopressin-

    2. KPDr. Karen Parker1:17:07

       Yes.

    3. AHAndrew Huberman1:17:07

       ... because there's a lot to discuss there. So you told us this is a molecule that chemically is very similar to oxytocin.

    4. KPDr. Karen Parker1:17:13

       Mm-hmm.

    5. AHAndrew Huberman1:17:14

       Um, is it manufactured in the human brain and body?

    6. KPDr. Karen Parker1:17:16

       Yes.

    7. AHAndrew Huberman1:17:17

       Okay. Do we know a subset of the sites that it's known to be produced and where some of its actions are?

    8. KPDr. Karen Parker1:17:24

       Mm-hmm.

    9. AHAndrew Huberman1:17:24

       I mean, you mentioned the kidney and the antidiuretic hormone-

    10. KPDr. Karen Parker1:17:26

        Right.

    11. AHAndrew Huberman1:17:27

        ... um, roles, but within the brain, like what brain areas have neurons that make vasopressin?

    12. KPDr. Karen Parker1:17:32

        Well, so the-

    13. AHAndrew Huberman1:17:33

        Or have the receptors for vasopressin?

    14. KPDr. Karen Parker1:17:34

        Yeah, I mean, the receptors are all over- are all over the brain, uh, and again, it varies depending on the species and, you know, the way the receptors are measured, uh, are in po- postmortem tissue, right, which can be very difficult to get good samples, right? And so we need to have that caveat going in. Um, but yeah, I mean, it's- it's made in the hypothalamus, um, and it's released all over the brain, and there's vasopressin receptors all over the brain, right? And, um, what's really interesting about vasopressin, I always sort of joke that oxytocin, you know, always saw its day in the sun, if you will, and the vasopressin was sort of the stepchild that was, like, left, you know, sort of behind. And- and the reason why I find this fascinating is, again, like, I think back to my, you know, my- my roots as a, you know, evolutionary biologist, behavioral neuroscientist, and what was interesting is that there were studies in the early to mid 1990s showing that vasopressin was critical for male social behavior. And so, um, there was work, you know, there was a variety of people, and I- I think Rob Malenka mentioned this on his- on- on the podcast he did about, you know, there's a- a group of people like Sue Carter, Larry Young, Tom Insole, some of these early people, and they gave vasopressin to male prairie voles, and ve- vasopressin was what induced, um, pair bonding, um, with a- a female mate, and also paternal care.

    15. AHAndrew Huberman1:19:03

        And- and as I recall, those experiments were done in the context of looking at, um, polygamy versus monogamy-

    16. KPDr. Karen Parker1:19:10

        Uh-huh.

    17. AHAndrew Huberman1:19:10

        ... of these prairie voles. Um...

    18. KPDr. Karen Parker1:19:12

        Uh, prairie voles versus, like, a different species, so same, um, genus but a different species. So it might be a montane vole or, you know, highly related, but these other species. So prairie voles are monogamous. The males-

    19. AHAndrew Huberman1:19:26

        For life?

    20. KPDr. Karen Parker1:19:27

        Uh, well, I mean, that was the part-

    21. AHAndrew Huberman1:19:29

        50% divorce rate.

    22. KPDr. Karen Parker1:19:30

        Yeah, that was (laughs) -

    23. AHAndrew Huberman1:19:30

        (laughs)

    24. KPDr. Karen Parker1:19:31

        I don't think it's that bad, but I think a large meeting-

    25. AHAndrew Huberman1:19:32

        They're doing better than we are as a species.

    26. KPDr. Karen Parker1:19:33

        (laughs) That's true.

    27. AHAndrew Huberman1:19:34

        Yeah.

    28. KPDr. Karen Parker1:19:34

        We should look to them for pointers.

    29. AHAndrew Huberman1:19:36

        And all the divorced folks are saying, "Wait, why'd you say better?"

    30. KPDr. Karen Parker1:19:38

        (laughs)

Episode duration: 2:56:27