How Psychedelic Compounds Improve Your Brain's Plasticity - An Interview With Julie Holland, MD

How Psychedelic Compounds Improve Your Brain's Plasticity - An Interview With Julie Holland, MD

What follows is a transcript for the podcast Homegrown Humans – Julie Holland, MD – Psychedelics - Hosted by Jamie Wheal.

Topics within the interview include:

  • How psychedelics rewire the brain
  • The role of mindfulness and psychedelics in accessing parasympathetic states
  • Hormones and love drugs for bonding, connection, and sexuality
  • The power of MDMA to promote healing through connection with others

Jamie Wheal: It is absolutely my stoking pleasure to get to welcome Dr. Julie Holland, a psychiatrist, a psycho-pharmacology, a bestselling author of "Weekends at Bellevue," "Moody Bitches," "Good Chemistry," right here your most recent, as well as a host of other books on psycho-pharmacology and the ways we humans feel and heal. A musician, a rock and roll queen, a wife and mother, and an all round advocate for good things, healing, common sense, research, and play in the world. Julie, welcome to Homegrown Humans, stoked to connect.

Julie Holland, MD: Thank you for having me, that was a lovely introduction. It's all true. All those things are true.

Jamie Wheal: Yeah. Yeah. Well, what I didn't know was true until we were most recently at a conference together was that how OG you were in psychedelic advocacy space, and that yours and Rick Doblin's relationship, the founder of MAPS, goes all the way back to the eighties.

How Julie Got Involved in Psychedelic Advocacy Space

Julie Holland, MD: Yeah, I met Rick in 1985. I got very involved sort of unknowingly in harm reduction actually when I was a teenager, because I accidentally ingested something different from what I was hoping to, and I can tell you that story later. I was really interested in drug policy from a very early age. I was a pre-med at Penn, my major, I love to talk about this because it's the reason I went to Penn. My major was called the biological basis of behavior. It was a combination of bio and psych and neurology, psychology, it was all about the brain. There was a concentration within that major, which was psycho-pharmacology. So at undergrad, I was very much studying drugs. I also minored in human sexuality, so I was actually studying drugs and sex, and I was fronting a band, so I was very involved in music.

But in 1985, I met Rick Doblin. I had read an article about ecstasy MDMA, at that time they were calling it Adam. And in that article, they mentioned and several people, Lester Grinspoon and George Greer and Rick Doblin. I was living in a fraternity that summer and I had access to free long distance calling, this was back when it cost money, long distance calling cost more. There was just a phone and a room, and I called Rick Doblin. I called George Greer. I called Lester Grinspoon. I found all these, this was before the internet, I don't know how I did this, but I had an amazing phone conversation with Rick. And then he came to visit me. I was living in a castle on Penn's campus. One of the fraternities, it was called the castle and I was living in a turret.

So he came to visit me and we actually took MDMA together right before it became illegal, the day before, basically. But it was probably my second time taking it, I think. The first time I took MDMA, I was really intrigued by how quiet my head got, and I thought about how many psychiatric patient could, if nothing else, if they could even just experience this quiet for an hour or two, how peaceful that could be. I've always been very interested in schizophrenia, and I had this idea that it would quiet the voices. That research still hasn't been done, and I'm really hoping that we can do a MAPS sponsored study at some point, a very small pilot study to prove me wrong or right. But basically, since June of 1985, I've been friends with Rick.

This is before MAPS.

Jamie Wheal: What was that experience in the turret like?

Julie Holland, MD: Rick tells the story very often about how his printer spit out this one single page, become more than a dream, which is true, it did. I'm used to printers doing weird things, so I didn't get particularly freaked out about it, but it is a great sort of origin story for our friendship that we both saw the potential clinical utility in this drug of abuse. And I was pretty sure I was going to be a psychiatrist, so I was very excited that there was potentially a new tool for psychiatry. It's one of the things that fueled my passion. When you are an undergrad and you're pre-med, and you're taking all these classes that you don't necessarily want to take but you have to, and then you have to take the MCATs and then you have to go to med school, take all these classes that you don't really want to take, that you have to, you need like a mighty lure to pull you through that process.

And for me, it really was the carrot at the end of the stick, which was doing MDMA research, educating people about MDMA. I edited a book called, "Ecstasy: The Complete Guide." It was actually the first book I did, it was the most important thing that I wanted to do, so I did that first. And what I did really with the ecstasy book was, I assigned chapters to every person that I had called that summer on the phone. George Greer did a chapter, and Dave Nichols, who I called, he did chapter, and Lester, I think I interviewed Lester and stayed in touch with him for a long time. That was my entree to the psychedelic research community, was assigning chapters for that book and staying in touch with everybody I had gotten in touch with in 1985.

Jamie Wheal: But that's no small thing. That is career suicide, if you're trying to do this peer reviewed, respectable psychiatrist route, for you to be flying your freak flag back then.

Julie Holland, MD: Yeah. Well, I've been really lucky in terms of career suicide and, maybe it's not luck. I am smart. I communicate well, I am easy on the eyes. I'm good at being a little flirty, a little manipulative, I'm not going to say I'm a schemer and I'm Machiavellian, but I often will play the long game with somebody and make myself a little vulnerable to solidify a relationship. I'm an adult human primate, we are programmed really as social primates to be obligatorily gregarious, that's how our species survives. So, it's never been career suicide for me, but it's always been right on the edge. I've definitely had, I had the psychiatrist I really looked up to like a mentor, this guy Jack Herskowitz.

And I said, "it's really one of the reasons why I ended up going to med school or doing this residency is because I really believe in this." And he's like, "don't say that it, makes you sound crazy." But he didn't say you're crazy. He was just like, "don't say it that way." So even then, he's trying to advise me. When I was at Bellevue, I had a job working Saturday nights and Sunday nights running the psychiatric emergency room at the Bellevue psych ER. And during that time I had a faculty affiliation with NYU school of Madison. And when I left the Bellevue job, I still had the faculty affiliation. It was still important to me to have that, if nothing else in the Chiron when you're being interviewed by CNN, it's nice if it can say assistant professor of psychiatry.

And in terms of career suicide, the closest thing I got to career suicide was that I went on the Bill O'Reilly show.

Jamie Wheal: You can end the sentence there, right?

Julie Holland, MD: Here's what happened. He asked me something about drugs, and I basically said that I thought that some drugs could be therapeutic. And he's like, "what are you talking about?" And I said, "well, I think that psilocybin or ayahuasca are potentially therapeutic." I didn't even say I'm MDMA, I don't know why I picked those two. But there was somebody very high up at Bellevue who happened to watch Fox news and watch Bill O'Reilly. And she was like, "who is this? Who is this NYU person? And what is she saying?" And then shortly after that, I lost my faculty affiliation and I became a free agent.

I was no longer an assistant professor of psychiatry. That was really hard for me. I felt betrayed by some of the faculty there that enabled me to be let go. I had dreams that I would always be at NYU, do psychedelic research at NYU, or do MDMA research at NYU, so it was hard. It was hard for me, but what happened right after that was that I sold "Moody Bitches" to Penguin Press for seven figures. And all of a sudden, it didn't matter as much if I had a faculty affiliation or not. And ever since then, I've been able to say whatever I want, I don't have any chairman or chairperson or board of directors, I don't have anybody telling me what I can or can't say or what I focus myself and put my energy into, except my Wrangler and spiritual bodyguard and husband, Jeremy Wolf.

If anybody's going to tell me what to do or not to do, or how to sound crazy or not, it's going to be him. The career suicide became sort of a non-issue. I did my residency, I worked for nine years at Bellevue. I've had a private practice for 28 years now. I've published five books. I love that I can say what I want. I love that I can speak my mind and speak from the heart. And my career is firmly ensconced at this point. I don't know what it would take to blow it up. I don't know, if somebody wanted to cancel me.

Jamie Wheal: But now you're on the other side. It's that JFK thing of, success has a thousand fathers and failure is an orphan. The psychedelic Renaissance is obviously completely blossomed, has been validated mainstream, Michael Pollan, all the things. So now, everybody's piling into this space. But just as a hat tip, and it's particularly to listeners, she might have been like, "oh yeah, I got into ayahuasca ages ago, back in that 2011 Nat Geo article, or I heard about it on a Rogan podcast." You're like, "you guys are infants." As far as the history of this movement, you've been in it and speaking your truth and dedications about it for a lot longer than it's just been trendy and sexy.

Julie Holland, MD: There's two things that reminds me of. One is, I always joke either with Rick or about Rick, this idea that, because we're playing the long game, we really need to watch our blood pressure and our cholesterol, it's going to take a long time, it has been going on for 30 some plus years. I just came from the horizons conference last weekend, and this thing has got a life of its own at this point. Obviously it's got plenty of momentum. It doesn't matter what I do anymore. A lot of seeds got planted a long time ago and they're bearing fruit everywhere. I was in the hallway at horizons and three people came up to me from a Montreal site, and they want to do psilocybin research and end of life.

And then I talked to three psychiatrists from Long Island, and they're interested in MDMA schizophrenia. And there's people everywhere doing the research, the ideas are out there. I know you saw me sit back like, "hey, you guys could do all the work now." The seeds were sown, everybody can reap the benefits now. The word is out, it's incredibly gratifying. But I also spent a lot of time at horizons on the stage talking about, we have some problems and we need to weed out these problems. We're all trying to grow something, and unrestricted growth in medicine is called cancer. Any good gardener knows that you really have to prune. You have to prune, shape and train the plants to be the shape you want them to be.

And just complete unrestricted growth, you're not going to get the most fruit. And sometimes when you prune a tree back, especially a fruit tree, you're supposed to prune those babies way back. They're ugly, you've taken a lot of the beauty out, but what you've left are the really strong wands that are going to grow and bear fruit. I feel like we're really in a pruning phase now, or we should be in a pruning phase now. There are issues, there are people who are misbehaving, and it's not my job to fix everything. And like a dentist, I'm just trying to see where the cavities are. And like I said at horizons, it's no fun going to the dentist. You do get nitrous, or maybe you could get ketamine, but it's painful.

They got to really dig out all the stuff that's rotten and then fill it in with something. But then the tooth is stronger, and all metaphors aside, we're definitely in a phase now where we need to clean up and make sure that we are being ethical and acting with integrity and not incorporating the, what are the buzz words? The patriarchal or capitalist sort of agenda.

Maintaining Ethics and Integrity in Psychedelic Therapy

Jamie Wheal: Extract, extract on this.

Julie Holland, MD: Right. We don't want to be extractive. We are really so hypnotized by some of these words and this idea. Somebody was talking to me about, well, "I don't think I wanted to go into this field because I can't get ahead in that field." And I'm like, "yeah, but you're in that field. You want to be in that field? Why do you have to get ahead?" Why does there have to be, she's looking for a job and somebody was saying to her, "yeah, but is there any room to move up?" And I get that's the way we think, but you don't have to move up.

Jamie Wheal: It's how you get a bunch of smart kids in the Ivy Leagues going to fucking Goldman Sachs and McKinsey. What is the fastest, slickest ladder to the top?

Julie Holland, MD: Right, and what's the next thing? And where's the top? Like that great World Party song, where is this top you speak of? There's no such thing. And there's this quote I love to say, but I'm blanking on it now. Oh, you can never get enough of something that almost works. You're looking for that validation and that thing that's going to be meaningful to you, but you're holding a cup with a hole in the bottom, it's not really going to work. And so, even though maybe I'm being hypocritical because I am also among the venture capitalist people and I am investing in the space, I am emotionally invested in the sort of psychedelic business space, but we would love it, I know I'm not alone, I'll say we, many of us would love it if it wasn't so patriarchal and capitalist.

And if it was more psychedelic, which is all about, as you know, a group mind or connecting with nature, connecting with the cosmos, connecting with the self. There's something very disconnected, and cancer, and I don't mean to say this in a bad way because it's not, yang and yin, we need them both. But there's something just very, very yang about the way these corporations are working, where they're carving out the IP, it's not communal, it's not United or unitive. A unit of consciousness, the best thing about psychedelics is that when you feel that bliss of connection, everything is connected and it all makes sense, or love connects all of us. I don't know if you've had unitive experiences, if you're comfortable talking about them, but I want to add that unit of consciousness to the psychedelic business world. I don't know if that's possible, but I'm going to make a plea.

Jamie Wheal: Let me play devil's advocate on that. Because within the, whether you call it the underground or the core psychedelic community, without a doubt, the enough ability of the psychedelic experience is the thing that has lit people up. The thing that has brought to take risks and prioritize, bring this into the world, it's very purpose based and mission driven. And, in some respects, you could say this is a continuation of mystery schools from ever back. Rick mentions the Eleusinian mysteries, there's obviously the [inaudible 00:18:45] break, mystical tradition, there's all sorts. And that idea of, we are initiates into something ineffable, profound, beautiful, and we're proselytizing or doing our best to bring it to others. And on the other hand, there's been pushback. And I think it was a Hopkins study, maybe five, six years ago, you probably were tracking this one, the ones about increased ecological awareness, all the kind of groovy pro-social qualities, but then the methodology was somewhat questioned.

Was there any P hacking? Is that really true? And then you get the Sydney Gottlieb's, the MK ultra CIA guys, you on one hand he meditated and he lived off the grid and he had goats and had a little farm. And on the other hand, he was doing horrendous prison experiments and all kinds of psychological manipulation. And then you've got the crypto tech bros who have had a handful of experiences, and in fact it appears that actually it's not eradicating ego and prompting unitive experiences, or if it is at a state level, not at a developmental level. And you're having almost inflamed narcissism, which was always one of the known issues in all of spiritual traditions, but now we're coming at it from a medical, psychological experiential level, so the more the merrier. What's your take on, throw in Aztec mushroom sacrifices, kicking it to the Grateful Dead in Marin in 1975 was super groovy and they're set in stone culture and milieu.

Julie Holland, MD: But then you also have LSD with the Manson murders. So, how can it be all these things? And, like anything in life, it's complicated and it's not black and white and it's not either/or, it's both. The joke that I've made, and I know Michael Pollan makes, it's an easy joke to make is, these are supposed to be medicines that dissolve ego. Why is there so much ego in this space? It comes back to, people are going to people. This field attracts strong personalities who've got quirky ideas and they're tilting at windmills. I think just because the psychedelics in and of themselves are so intense and they're catalysts, it's going to bring in some particular types of people.

There are a lot of narcissists in this space, and there are a lot of these sort of yang personalities. It has nothing to do with men or women. A lot of the women I've met in this space are, I was at Esalen in a hot tub full of women in this space a few years ago before COVID, and we all admitted to each other, it was seven women, and we all admitted to each other that as children, we had not identified as men, we had identified as tomboys. There was a space for us where we were bossy girls and tough girls, but we were girls.

None of us had gotten sex change, reassignment surgery or anything like that. But this idea of a tomboy to me is incorporating the yang into the yin. And it doesn't matter what gender you are and, the yang is this sort of, go out there and get it and then come back and see if it was the thing you thought it was. And the yin is, let's learn about what the thing is and, and be open to it when it comes to us. It's this very, very different kind of energy.

Jamie Wheal: Can you play that game without getting steamrolled by the yang?

Julie Holland, MD: Yeah.

Jamie Wheal: That's the question. Do those quieter voices, does that longer game, more organic thing, basically it's permaculture versus clear cutting.

Julie Holland, MD: Yeah.

Jamie Wheal: And how do you have the longer, slower game have the chance to thrive in the face of-

Julie Holland, MD: I just feel like, because of the culture we're living in, you can't take the people out of the culture, and the culture in America, or certainly in the New York city gatherings that we went to, or the Miami gatherings, it is a lot of yang capitalist driven. And the model, something I heard a bunch at horizons was, these guys are pharma companies. What do you expect from pharma companies? And you're talking to a psychiatrist. What I expect from pharma companies, what I've seen since I've been an undergrad studying prescription medicines and drugs of abuse and obviously in med school, psych residency, I have seen pharma companies behave unconscionably. So evil, so bad, surprising me over and over again by their bullshit games and the bottom line and what they would do to get that.

So if these psychedelic companies are, "oh, they're just pharma companies," that's the perfect sort of excuse. It's like, boys will be boys, that's how pharma companies act. It's true. It is how pharma companies act. But we in the psychedelic community who care about or say we care about the environment, the indigenous population, marginalized societies, we want everybody included. We want diversity and inclusion and group and hugging. But it's so yin and diffused, what we want, versus the yang capitalist greed machine, where it's normalized, that's how they do it, this is how you get patents and defend your patents. I get up on this-

Jamie Wheal: You get patted on the head for being hopelessly naive for suggesting there might be a different way.

Julie Holland, MD: Yeah.

Jamie Wheal: Like, "oh, you just don't understand the way the world works, honey."

Julie Holland, MD: Yeah. I would rather be hopelessly naive and not understand and keep insisting about how people should act than be steamrolled and just sort of accept, this is bigger than me and I can't fight it. I don't mind tilting at windmills, I have nothing better to do. And like Rick who sort of wanted to change things from the inside out, I decided, instead of pretending that this whole sphere doesn't exist, corporate [inaudible 00:25:06], there's so many people who are just don't want anything to do with the corporations. They're furious, they're throwing up their hands. I would rather get involved, know who the players are, steer my friends to the people that I think are more ethical. I've chosen to throw my lot in with a couple different people and companies, I'm medical, I'm advising for a VC company called Palo Santo.

They were vetted for me by Double Blind, which is a psychedelic magazine that I like on the west coast. I met a lot of VC people and the guys at Palo Santo, I really feel like get it and they care and they're ethical and they're good people. I've decided to try to help them and maybe steer some of my friends who are developing companies to come to Palo Santo. There's a bunch of VCs in this space, some of them are more collaborative, others are more sort of.

All of them are more collaborative, others are more sort of cut-throat.

Jamie Wheal: And they've already adopted an appropriate, everything you just said about indigenous, and inner cities and diversity and equity, and all of the kind of things and the give backs, and some are sincere, and then a whole lot of...

Julie Holland, MD: The companies.

Jamie Wheal: It's lip service. And you look at their business models, or their pitch decks, and you're like, guys, riddle me this, how are you going to take... Masculine to market? And that $100 million bucks in a decade, and serve inner cities, and give back to all the indigenous populations that might have ever had any affiliation with that molecule in any shape or form, and give 10x returns to your A round investors. You're like [inaudible 00:26:43] pick a few, but you don't get, you cannot do all of them.

Julie Holland, MD: It is this question of whether people are really walking their talk or not, and I wonder who's going to keep an eye on who says they're doing, and what they are really doing. Some... I get calls a lot from people who want me to sort of work with them. And I think part of it is just they need a woman on their website. I'm a woman, I have an MD, I'm not a woman of color. I don't have any indigenous background, I'm a Jew. You could make a case that we've been oppressed at some point, but clearly these days, we're not really... We are if anything, probably in a more privileged position. So, but anyway, my point is I get asked a lot to be on this company or that, and sometimes I'll get on the phone with the CEOs and they're saying all the right things, and I realize it's just they're assistant outlined Good Chemistry for them.

And they're just ticking off the boxes of things that are important to me that I've written about. I'm afraid that, that's kind of what it is. And I sort of got charmed at first and then I was like, there's something weird about the order that he mentioned all these things, and I'm like that makes more sense now. But there are some companies who're saying that they're giving back who are... I hope that they're saying what... That they're doing, what they say they're going to do. There's no end to the imbalance of sort of the people who really need this versus the people who are getting it, or are going to get it.

But it's the same thing in psychiatry, Moody Bitches is all about how women are over diagnosed, over pathologized, over medicated. And yet you could totally flip it around and make a case that there are just as many people who are really psychiatrically ill, who have no access to psychiatrists where there's too much stigma. They're not on meds, they're not properly diagnosed, they're sick and they're harming others while they're sick. So, like I said, it's often both things and not one or the other. Everything, if you look big enough is, you think it's white and it's black it's, and I think...

Jamie Wheal: Anybody who's trying to do big scale for philanthropy, you start out with prisons or you start out [inaudible 00:28:55] you start out with whatever and people almost always end up back to fuck, you've got to get back to education with the kids. Broken humans or broken hurt people. And how do we get back to fix that? And it almost always regresses back to like Montessori school for everyone.

Julie Holland, MD: No, it's true. I used to at Bellevue... The joke was, so was the patient needed a childhood transplant? Is that what we're talking about here? Because everybody that came into Bellevue psych ER... I actually got to a point where I said, I don't need to hear the heart-wrenching backstory anymore. I'm just going to accept that every single person that walks through these doors has had a terrible childhood. They have been sexually abused, physically abused, neglected. It's a given. So I agree that you do... That is probably the best place to break the cycle is with super early childhood intervention. From doula on for the first two, three, maybe five years.

It's good to front load things and then you don't have to work so hard later. We, a lot of us who had kids in the 90s or 2000s, we did attachment parenting and that's... Maybe they don't still call it attachment parenting, but it is this idea that if you put in a lot of time in the first few years, you're not going to have to put in so much time after. And that was my experience.

How Psychedelics Rewire the Brain

Jamie Wheal: I'd love to peel back the layer because this was a great update on the state of the union, the state of the world, the field of psychedelic therapy and its intersection with psychiatry. And my sense is is that there's a shared thread. There's a thread we share from your books, Moody Bitches into Good Chemistry in particular where you're sort of saying, hey, underneath the hood of the psychological experience are the endocrine, hormonal, neurochemical substrates. And you spend quite a bit of time unpacking the serotonergic system, which is obviously where Prozac as well as many of the tryptamine class psychedelics like LSD and [inaudible 00:30:55] and MDMA. As well as the endocannabinoid system. And the sort of parasympathetic system in our bodies, including I'm imagining the vagal nerve, and those sort of things.

So, and obviously I just wrote quite a bit about, dedicated the entire middle section of my book to those things. Hey, even if... Let's assume that the psychedelic Renaissance as it's getting press is already captured by big pharma and by the market branches, but that's not the whole story. There's still an underground, there's still... there's both sacramental use underground use, all of these things. And what's as interesting as anything else is that psychedelics gives us really good research opportunities. You get to put somebody in a specific compound in an MRI machine or hooked up to [inaudible 00:31:40] or whatever it would be. So we can precipitate known states and track them. And now we're under the hood to the knobs and levers of our bodies and brains. So I'd love to just hear your thoughts on it.

And many of our listeners will probably appreciate just walking through some of these things. So let's start where you were talking. So, why is it and how is it that the serotonin system can both do something like numb you out and just clip all your peaks and valleys with something like a Prozac and SSRI? And on the other hand, can you shoot the moon on something like an LSD, or hit that happy middle band with something like MDMA. What do you... How do you tease apart those different mechanisms of action, because they seem so wildly different and yet all important for us to make sense of?

Julie Holland, MD: Well, the first thing I would say is that it's incredibly complicated and if we could understand it, it wouldn't be incredibly complicated. The brain... The more we look, the more we figure out that we don't know. And when I... Back when I was in med school, we only had three serotonin receptors. We keep finding more and more and subdividing them. The short answer with why Prozac is different from MDMA or the classical psychedelics is that the SSRIs... Even though the S either stands for specific or selective, depending on what you paid attention to back in the 90s, but it's a selective or specific serotonergic, which is already nonspecific, reuptake inhibitor. It just blocks the recycling, it doesn't do anything else. So, it is sort of a non-specific increase for presynaptic serotonin. Whereas the way the LSD gloms on the 5-HT2A receptor in particular, it doesn't just get onto this very specific receptor, but the receptor kind of cups it in there and it really holds on for a while.

Then psilocybin hits that receptor it doesn't hold on for as long. But the serotonin from Prozac is just nonspecific. It doesn't just go to 5-HT2A, it's going to go to all the other serotonergic receptors as well. But there was a time when I first understood the way that MDMA worked where it was a little confusing, why is this illegal? And then why is Prozac legal? They're sort of doing the same thing, but they don't completely do the same thing. And the bottom line is the first time somebody takes a Prozac, they don't feel really good. And wonder if maybe they can do this again sometime soon. And it's just, it's not that immediate and that's one of the ways at this point, we all sort of... Some things are drugs, some things are medicines.

We call what other people would say are drugs, those are plant medicines. And then what most people say are prescription medicines, you can also call drugs and what's the difference? And one of the ways that I sort of think of the difference is drugs act immediately, and either four hours or eight hours or 12 hours, and then it's over. But the medicines, you take them every day and after a while they sort of build up and start making these changes. So that's my [crosstalk 00:34:54]

Jamie Wheal: My favorite neologism was hearing some podcast pros down in Patulum talking about party medicines. And I'm like, oh, that's an interesting new case.

Julie Holland, MD: Nice. Right? So, in Good Chemistry, what I was trying to get at is this idea that when you're in the parasympathetic, when you're feeling held and cared for and loved and attended to, that is a very particular pharmacological cocktail. And I would say it's different for everybody. But it's also very different from being in fight or flight. And everybody knows what fight or flight feels like. And also everybody's heard about fight or flight for... I was taught fight or flight a dozen times from middle school to medical school. It was always explained, the rapid heart rate and the sweaty hands and all this stuff. And it was explained, this is how our species survives.

We either fight or we run away. And the... What Good Chemistry was about is, that's bullshit. That might happen 5% of your life if you're unlucky. But the truth is where you're supposed to spend most of your time and where you really thrive is when you're not in fight or flight. Your social skills suck in fight or flight. And if you don't have good social skills, no one's going to help you. They're not going to share the kill with you and feed you. They're not going to help you build your lean to, you're not going to survive. Back in the Savannah, if people didn't like you or didn't have good social skills, you could easily die. And so being in the opposite of fight or flight means that your social skills are better. You can learn, you can integrate.

It's the only time where you can rest, digest and your body can repair itself and you can repair your social relationships. So Good Chemistry was all about what is this parasympathetic? What's the chemistry of parasympathetic? And it's not just one thing, right? It's everybody's kind of proprietary blend of however oxytocins going to make you feel good, right? Oxytocin may or may not feel good on its own, but what we do know is that it enables these cascades of feel good hormones and neurotransmitters like endorphins, like endo cannabinoids, right? I get... I spent a lot of time on research for Good Chemistry, and if you go to and you click on Good Chemistry, there's 40 pages of notes, of scientific articles, book chapters, to sort of support what I'm talking about. I found a bunch of articles on how oxytocin works through the endo cannabinoid system, how oxytocin works through the endorphin system, how it also increases serotonin, dopamine...

Jamie Wheal: So, is it also sort-

Julie Holland, MD: [crosstalk 00:37:30] all the good stuff I mean, it's not really one thing. But if you look at a baby who's nursing and how relaxed and slack jawed it looked, you might say that baby looks very opiated. And it's true that there is a real increase of... Just sucking releases endorphins. And if it didn't babies would die, right? If sucking didn't feel good, you're not going to make it. If eating didn't feel good, those are just very basic things that they have to wire the brain a certain way. And there's actually a lot of the endo cannabinoid system that's involved with developing the musculature for sucking. So it's all kind of recursive. That when I started looking at the stuff, I loved it. And the other thing that I loved is I discovered that these receptors made. They form dimers, a receptor complex, a serotonin like a 5-HT2A receptor, right? Which you could think of as a psychedelic receptor. When it gets stimulated enough, it makes a receptor pair with the oxytocin receptor.

Jamie Wheal: So now is oxytocin a signaling molecule in that whole shebang or is it rising? [crosstalk 00:38:39] on nitric oxide, right? His whole point of blood brain barrier and the notion of what nitric oxide does in that is, is oxytocin in a similar category to that, or is it kind of a distinct in doing a sort of third differentiator?

Julie Holland, MD: So oxytocin is two very main things. Again is it one, is it the other? No, it's both. And probably more. So it is a hormone that works throughout the body, right? A hormone goes into the bloodstream, works in a different part, right? And a neurotransmitter just works right next door within the brain. So oxytocin functions is both a neurotransmitter and a hormone. So it's everywhere you want to be, especially if you're a woman. It will allow you to nurse and to bond with your baby. It will allow you to push a baby out of your uterus, right? That's totally a high oxytocin state. [crosstalk 00:39:29].

Jamie Wheal: Pitocin, right?

Julie Holland, MD: Pitocin. Exactly. If you want to induce labor, you give oxytocin. It is very much involved with nursing. It's also very much involved with orgasm. One of the things I wrote about in Moody Bitch is, is you may think that you have a casual hookup, but if you are a woman and you have had an orgasm with somebody, you are going to have a squirt of oxytocin in your brain, that's going to make you sort of more open and trusting and by bonding with this person who just helped to bring you to this somewhat difficult to achieve state.

Men also have an increase in oxytocin after orgasm. And one of the things I posited in Moody Bitches when I was writing about porn, is are we bonding with our laptops a little bit right after we climax? Because...

Jamie Wheal: I love my Apple products.

Julie Holland, MD: Because if you have a little oxytocin and... Right, exactly. So I don't know for sure. That was just sort of a... Not a rhetorical question, but I did write quite a bit about porn and shaving pubic hair and all sorts of things in Moody Bitches. I had things to say about women in society. And just as a physician, please don't irreversibly remove your pubic hair, you may want it later. Because there are a lot of people who are getting laser hair removal.

Jamie Wheal: Well, but there was an interesting article in the New York Times, right? I feel like it was maybe an op-ed, but it was, it was some professor who was basically discussing first wave, second wave, third wave feminism. And that... And basically just asking, I suppose it was kind of Gen Z college women, hey, are you kind of happy with how this is all played out? The whole swipe right. No slut shaming, more choices and more everything is just better. And they were sort of like, no, we don't like this. We've been sort of sold the bill of goods. And it was almost kind of a sort of erosion of that, just sort of structuralist sex positivity. Because there was a sense of an erosion. It sounds like you're speaking to maybe some of the deep structural things, things that might be sort of more perennially true than just sort of a girl power girl bus, kind of take on all that.

The Drugs We’re Being Offered and The Direct Link Between Hormones and Mood

Julie Holland, MD: Yeah. Well, there are some things I think... I have a 21 year old daughter, and there are some things that I'm like, you're so lucky you're growing up now. So much worse when we were... In some ways I think that their generation has got things better and easier. I would say with body positivity, they really have. I definitely grew up in a time where you wanted like big boobs and a small butt, and that's just not my lineage. And there was not a lot of curvy, thick is good, that that was not my childhood. But luckily for my daughter, I think there's just a lot less body shaming and a lot less lot less slut shaming, and that's great. But this, the bottom line is that we are really built for connection. And a lot of the hookup sex is about having not much intimacy and not much connection and being okay with that. And it just, it honestly just kind of goes against our wiring.

And then the other thing I wrote about in Moody Bitches is this being sort of over medicated. Being on antidepressants, anti-anxiety meds, sleeping pills, all the things that women are on, but also being on birth control pills. That's a very non fluid sort of stable, static, non fluctuating way for a woman to be. And we really are naturally fluid and dynamic, and we feel different ways at different times of the month. And it serves us in different ways. And so if you're on the pill nonstop and you're on antidepressants nonstop, you're just, you're not having any kind of that flow and you get a little stuck. And also there's really... I don't want to say encouraging. There's evidence that suggests that this combination of antidepressants and birth control pills makes it so that you don't really care if you're coupled or not.

Julie Holland, MD: You're not going to pursue someone, you're not going to fall in love. One of the things you need to fall in love is you have to be a little bit obsessive, a little bit delusional. And if you're on a medicine to prevent OCD, you're not going to get that obsessive, I'm really into this person. I'm thinking about them all the time. You're going to miss that. And then there's this whole issue, whether the birth control really interferes with pheromone detection and processing, which I know is a little bit woo, woo. And out of bounds for some people. But I absolutely believe in the power of pheromones, and the power of smell to help with...

Jamie Wheal: That's not woo woo.

Julie Holland, MD: To help with mating. Whether the pill really interferes in how, and whether that matters. I think it's still a little bit up for grabs because it hasn't been a highly replicated study.

Jamie Wheal: And is that the one where-

Julie Holland, MD: I mean, there, look-

Jamie Wheal: Women on the pill will choose a basically sort of better partner, domestic housemate. And then when they go off the pill, their hormonal reset and they sort of crave testosterone strong jaw.

Julie Holland, MD: Exactly. Right. So you end up with somebody... So the idea with... From what I understand of pheromones, but the reason why I say woo woo is that there's some people who feel like humans don't have pheromones. This is all bullshit. There are people who are just like this doesn't exist. I'm not one of those people. The pheromone detection, from what I understand is based on the sort of same compatibility issues when you give a kidney to somebody. It's called an NHA compatibility. And the idea is, if I'm immune to five things, and my lover is immune to five things, maybe our kids will be immune to 10 things. And won't that be great? But if we are immune to the same five things, we're not creating vigorous hybrids. So you have this detection system so that you can find people who are a little different from you, enough different from you, that your kids are going to have more protection.

And so what happens with the pill is that you end up picking people who are too similar. Who are more like your brother than another, that's one issue. Then this other issue of testosterone, chisel, chin, low voice, maybe more likely to cheat on you. Those guys, they have a name tag of cad instead of dad, right? The guys who are more likely to be a dad, aren't going to screw around. Maybe they're not as testosterone-y. Maybe they're a little lower in testosterone, and that's why they're going to stay and help you raise the kids. Right? So you're better off picking a dad when you want to have a kid and you're better off picking a cad. If you just need a sperm donor or just sex, and you don't really want him to stick around and raise the kids. But the birth control pills actually make you more likely to pick a dad than a cad. Maybe that's not bad, I'm rhyming.

Jamie Wheal: Right. That's a little Dr. Sexy Seuss.

Julie Holland, MD: Is it bad to pick a cad or a dad, you've been had.

Jamie Wheal: That's right. Yeah.

Julie Holland, MD: I think that a lot of women in their twenties are really attracted to these sort of bad boys who don't give them what they want. When you never get enough of something that almost works. So you keep going back and they keep sort of on... It's not a satisfying partnership. And a lot of times what happens with a woman when she starts to get into 30, 31, 32, there is a little bit of hijacking that happens and the estrogen really starts convincing your brain, that the priority is not a sexy guy, but somebody who's going to help you raise kids. If that's where you're at, and that's what you want.

Jamie Wheal: Just relationally, the number of friends we've known who have gone through their twenties in some kind of really powerful, meaningful, potential soulmate connection with all the fireworks and the drama, fracture. And then it's almost like musical chairs timer. The next semi likely candidate come that window, bam, and it's marriage that they hope will paper over any of the lack of all the other stuff. And then kids within 24 months. And you're just like, wow, this is just nakedly predictable.

Julie Holland, MD: Yeah. Well, it's nature. I mean, biology, look, I'm very biologically oriented. I mean, I was, I was hypnotized by... Brainwashed for four years at Penn biological basis of behavior. So it is all biology world for me. I mean, I have a lens that I look at things as we are social primates. How do primates act? What is a dominance hierarchy and what is a social structure in other primate societies? Because we are a primate society. That's one thing. And then I also look at how are the hormones driving behavior? But one of the interviews I did with Moody Bitches is she reminded me of something really important that I kind of forgot. She's like we all got into this habit of saying this hormone causes this behavior, but it's really not that simple.

It's not like if I inject a woman with testosterone, she's going to get horny, although she might. But she's not going to get horny in a vacuum. The thing that will actually give her her own testosterone levels is if some hot guy comes around, she likes the way he looks and he smells. That gives you your own testosterone and then you're horny. So sometimes you need a stimulus, or a releaser to get those hormone levels up. It's not like, I have increased testosterone, therefore I'm horny. It more is like, I saw a guy who made horny and now I have increased testosterone levels.

Jamie Wheal: Yeah. Well, actually, because as you were talking, I was thinking of Addyi, the female Viagra pill that kind of crashed and burned to much high and chagrin. And that sort of the upshot at least of the press coverage was women aren't that simple. Right. And you're seeking these kind of mechanistic... In fact, who was the fellow? There's a fellow, who's the Ob gyn. He was at Harvard, he's based in Aspen who was on that study. I can dig out his name again, but we were at a conference together. He's like, basically men need a place and women need a reason kind of thing. And but now let's go back to your biomechanics, right. If you were to... Let's assume, there is no one stop shop single pill for a woman's arousal, meaning, et cetera. But if you were to lightly juice their testosterone levels, if you were to give them low dose, micro dosed ED drugs so you have boosted nitric oxide and potential vasodilation and engorgement. If you were to kind of create some of those things and then you put them in a certain setting, would that not be potentially helpful?

Hormones and Love Drugs For Bonding, Connection, and Emotional Intimacy

Julie Holland, MD: It would be helpful. And the other thing that may be helpful is just a smidge of 2-CB. There are some psychedelics that are more likely to have you sort of feeling sensual and liking the feel of things. People had this idea that MDMA was a great drug for sex, but in reality, it's a great drug for bonding and connecting and having some emotional intimacy. But there are some hydraulic issues where it's not really a great pro sexual drug. But I sometimes [crosstalk 00:50:18] I think about how to design a pro sexual drug. Well, there are definitely some companies that are really looking. I've looked at so many decks, Jamie, I can't tell you. All these companies and their decks of what they're proposing.

There are several companies I will tell you, and I'm not going to name any names, who are looking at 2-CB for women and sexuality. And I think that there probably is something there. I mean, I don't think there are too many other psychedelics that make you sort of particularly interested or open to sex, but 2-CB... And my experience does and other people's experiences does. I mean, Sasha Shulgen sort of said that 2-CB was the sexiest, or the most sort of sensual of the phenethylamines he had looked at. What was... I can't remember what the drug was called that they came out with for women, but there were a lot of problems with it. One of the problems with it was you couldn't-

Jamie Wheal: Addyi.

Julie Holland. MD: Addyi. Yeah. You couldn't have alcohol with it. So unfortunately, I think a lot of women are used to having a drink or two before they're with somebody because it sort of takes away their inhibitions. They feel a little cloudy or separated from themselves. They can do crazy things they wouldn't typically do. So I think that was a real deal breaker for a lot of people. It wasn't a well tolerated medicine and I don't think it worked particularly well. I never prescribed it for anybody. Nobody ever asked me for it. I did prescribe testosterone every once in a while to a patient who wanted, but very low dose. One of the things I would say about testosterone for my patients is they would... What are the side effects? And I'm like, well, it can make you a little more hairy. It can make you.

They were like, "What are the side effects?" I'm like, "Well, it can make you a little more hairy. It can make you a little more pimply. It can make you a little more cheating on your partnery." The thing people sort of forget about testosterone, or they don't tell you, is that it really is a hormone of novelty. You're not necessarily going to be romantically inclined to the prince who's charmingly slumped at your side. You may be looking at some other Prince Charming or knight in shining armor that you think could actually provide you with a more vibrant, vigorous hybrid, because it really, even though you don't want a baby, your body's trying to mate with the best genes.

Somebody that you think is sexy or whatever, it really comes down to your body is like, "Oh, those genes would maybe work with our genes." It's not conscious. Obviously, hi, I'm attracted to your genetic material. Come with me.

But so anyway, testosterone for women, it can help them be more interested and have more libido and also estrogen can help you be more receptive, but it's all a little bit of a balance.

It's tricky because different people have different things that turn them on. You can be very internal and you have visualizations or stories that make you excited, but you're with somebody who wants you to talk or they want talk. What do you do with that? You could be aroused by some things and they're aroused by other things.

It's incredibly tricky, especially because novelty is so reliably something that will bring about libido in men and women. What do we do with these long term relationships or with the same person for 12 years, 30 years? As you probably know and I certainly know, I mean, Jeremy and I are considering to trying to write about this is like, how do you keep the love alive? One thing that can reliably increase testosterone is competition, arguing, fighting, trying to get the last word in.

Jamie Wheal: Smashing dishes, the Lucille and Ricky Ricardo thing?

Julie Holland: Right. This idea of makeup sex that after you separate and you have a big fight and then you get together and it feels better. There are all kinds of ways to change the pharmacology so that you're aroused to somebody. The truth is, and I wrote about this a lot in Moody Bitches, where you are in your cycle has a lot to do with whether you're going to be very receptive to sex or not. God help you if you're dealing with somebody perimenopausal or postmenopausal because where they are in their cycle is anybody's guess. It's super complicated. I will happily try out any medicines that are purported to be pro libidinous and pro sexual.

Jamie Wheal: What about GHB, because that that was available at nutrition stores and that kind of stuff and then it's now just scheduled a narcolepsy drug.

Julie Holland, MD: There's a lot of things that work better for men than women, is what I will tell you. GHB, gamma hydroxybutyrate, but the GHB also stands for good hard boner. It usually really helps with erections, but makes it a little harder to climax. Anything that makes it a little harder to climax is just not going to be as good for women as for men. Men often want to last longer. I don't know too many women who want to last longer.

There are a lot of things that you may think are pro sexual and that maybe [crosstalk 00:57:46], but for men, not women.

Jamie Wheal: [crosstalk 00:57:50]. I've heard the strongest endorsements of GHB from women.

Julie Holland, MD: From women?

Jamie Wheal: Yeah, who it unlocks something more primal, more disinhibited and centrally attuned.

Julie Holland, MD: The disinhibition is a really big deal, taking the breaks off. It's not just that you need gas, you need no breaks. I would say a lot of men, when they think about what's a good drug for a woman, they're thinking gas, making her more horny. But it's true that a big part of it is just taking off the disinhibition. This is why people like ambient sex.

Jamie Wheal: No way. Or you serious, Ambien sex?

Julie Holland, MD: Have you never heard of Ambien sex?

Jamie Wheal: I'm clueless.

Julie Holland, MD: Where have you been?

Jamie Wheal: I've been living under a rock.

Julie Holland, MD: Ambien really disinhibits you tremendously. Some people will take Ambien and have sex. They may not remember the sex they had so you really need to make sure there's consent and you're with somebody you trust because you really may not have a full recollection for the event. Ambien kind of turns your brain to Teflon a little bit. Then there's some women ...

Jamie Wheal: Doesn't it have a pharmacological [inaudible 00:58:48]? Is that some weird molecular thing?

Julie Holland, MD: I don't know about any correlation between Ambien and Ibogaine. But I'm certainly curious about that. That is news to me.

Jamie Wheal: I feel like Hamilton ...

Julie Holland, MD: Send me the article.

Jamie Wheal: I feel like it was one of, it was either a Hamilton wrote [crosstalk 00:59:03].

Julie Holland, MD: Have Hamilton send me the article.

Jamie Wheal: I was just like, "Whoa, that is [inaudible 00:59:07]."

Julie Holland, MD: Ambien or just alcohol. A lot of women, they'll get drunk and they're more likely to have sex and they're also, don't forget more likely be like, "Oh, I don't remember. I was drunk," because there is this, as much as we're talking free love or whatever, there's still some stigma. There's still some shame. A lot of people have shame about sex, about climaxing. Maybe you can have sex, but you couldn't possibly let someone see your orgasm face or whatever.

I mean, it's much more complicated for women, pharmacologically, psychologically. There's more shame around sex for women than men, absolutely. Shame is a big cock blocker, if I might say. This idea that that GHB sort of gets them a little bit outside of themselves and a little bit looser, a little bit disinhibited, then yes, it's probably going to help some women feel more interested in sex or be more able to climax.

Jamie Wheal: Because I mean, your question about how do you perpetuate positive feelings, polarization, last attraction, that kind of thing, and longer term relationships after evolutions had its fun with us. It doesn't really care. That was actually the study that we published in the book I just wrote, Recapture the Rapture, which was 10 couples for 12 weeks against six metrics or two for peak state. We did the mEq 30 and we did a flow scale inventory, so sort of intermittent flow during your day, but also actual mystical states.

Trauma, we did the PCL-5, so self-administered and [inaudible 01:00:36] ring based HRV. At a physiological level, RUD fragging and then also at a historic macro trauma level, are you processing? Then relationally, it was the iOS intimacy of self and other, how close intimacy are we feeling? Then that the PANAS scale. The results were meaningful. Women quite often compared to the men often actually had understandably given in our social constructs, had more initial trauma, but more change. They had higher mystical experiences if they had them, once you kind of weeded out the non-responders, those kind of things.

The results were really comparable to even a little bit stronger than some of the maps psychedelic therapy results. You're like, "Oh." The reason we kind of came into that was a conversation I had with Rick at the Battery Club way back three or four years ago. He's like, "Yeah, the closest thing we've seen in the MDMA PTSD work, the closest analog neuro physiologically, was post orgasm.

Then we kind of went to Nicole Prause’s work. I know you've been writing on porn, Nicole's done quite a bit of work and they might not quite line up, but she's been studying orgasm for women as prescription pharmaceutical for anxiety, insomnia, pain, all of those kind of things.

Julie Holland, MD: Right. Well, back in the day, that was a real treatment. That was a real treatment for women's malaise. I mean, they called it hysteria or something else, but I think it helps sometimes. I have a patient who is extremely tightly wound and miserable and can barely take a big breath and she's in her 40s and she's never climaxed. I really feel like that potentially a big part of her presentation and her issues.

Julie Holland, MD: But it is true, post orgasmic is when the oxytocin comes up. MDMA we know enhances oxytocin levels and functionality. I mean, that is sort of an early study that I hang my hat on and remember that MDMA reliably increases oxytocin and for most people reliably induces a state where you are more willing to bond and trust and connect and be intimate. That's a lot of the oxytocin.

But then obviously it's a methamphetamine at heart. You still have that increased dopamine where you want to sort of talk and connect and figure things out. Because of that increased dopamine, you have really good attention and concentration and sort of impulse control. The serotonin allows you to sort of have this sense of satiety and calm so that you feel sort of strong enough and able enough to really look at the trauma and dig down.

The thing I say about MDMA is I couldn't design a better medicine to facilitate trauma processing and psychotherapy because not only are you awake and alert, and you remember what you're talking about, and you're looking at where you got hurt in the past, but all that oxytocin makes you really trust the person who is doing this work with you, which means that when you get together in the next day, in the next week, in the next month, you still have that therapeutic alliance, like this person's helping me. I'm not going to work against them. We're going to work together. That's huge.

That's one of the big predictors of whether therapy, just regular psychotherapy, has a good outcome or not is what's the therapeutic alliance and how strong is it? Sometimes I think about marriage as a therapeutic alliance. Your partner, if they've known you for 20-30 years, this is not my quote, but they have the blueprint for your growth. I have the blueprint for Jeremy's growth. He has the blueprint for my growth. Why can't you be more like me? He's not like me, he's like him. But if he tries a little this way to be a little more like me, and I try a little bit to meet him in the middle, we both end up grow growing and having more of a repertoire of behaviors.

In some ways, your relationship partner or lover ends up being your therapist and how close you are and how much you trust them is sort of what the therapeutic alliances of about and whether your relationship is going go well or not.

Jamie Wheal: I mean, you can for sure, hot wire revolution. I mean, either it leads us into the ditch with seven year itches and affairs and all these kind of things on the sort of the novelty push for robust gene pool, or you're like, "Oh, whoa, there's [inaudible 01:05:10] we can reclaim, and we can use them to expand non-ordinary state experiences, profound cathartic healing experiences," which is, AKA equals novelty. It's a little bit like learning to juggle chainsaws while doing the tango.

It takes some time and practice so you can't just swap out your long term partner for some hookup at last call, right. You should kind of doubling down on that therapeutic blueprint. It's ours to do together, and we're going to places we've never gone before. I'm no longer looking over my shoulder looking to swap you out for something new and shiny because we are explorers together, which feels like ... You also the inevitable byproduct to this is quite often kids and a family unit. You're sort of like, and so any gold we find is going into the family kitty. It's tightening the parental bonds. That's doing all kinds of things. It feels like that's a [crosstalk 01:06:06].

Julie Holland, MD: We know that at least fathers of young babies, their testosterone goes down so that they are more likely to want to sort of ... They've got more, sorry, I blank on the, vasopressin. The vasopressin goes up, the testosterone goes down. It's all very simplistic, of course. But it's just this idea that there are biological adjustments that get made to a new father's chemistry so that he is more likely to want to stay, protect the baby and less likely to want to go out and screw around.

But that seven year itch is totally when baby doesn't need protecting any more. Maybe the genetic imperative that I spread my seed is what should take over. We definitely had a seven year itch thing in our relationship. No question. I think a lot of [crosstalk 01:06:54].

Jamie Wheal: Right around on time, like [crosstalk 01:06:55]?

Julie Holland, MD: Not exactly on time. Not exactly on time, but close enough. Then the question is then what? What happens after that? Because there are going to be breaks. There are going to be breaches and boundary violations and transgressions. Then the question is, do you stay and try to fix things or do you leave?

To me, this is another fight or flight yang versus parasympathetic yin is that staying and not running away and working through what happened and you did this because I did this, I did this because you did this and all the ... Anne Shogan calls that emotional ledgering. It's like, "I did this because you did this." It's all this kind of tit for tat. One of the things she says is that MDMA throws the ledger out. None of that shit really matters.

Jamie Wheal: Wow.

The Power of MDMA to Promote Healing Through Connection With Others

Julie Holland, MD: Let's get down to the deeper stuff. I'm absolutely believer in MDMA really helping couples work through their issues. I was a medical monitor on the MDMA PTSD couple study. That study was really important to me because it was the first time that the sort of government didn't just allow us to give MDMA to people with PTSD, but they allowed us to give MDMA to people who didn't have PTSD, who were adjacent to the PTSD sufferers, so people who were in a diad. One of them had PTSD and one of them was staying with them and trying to help them. To give both those people MDMA so that they can just have a good sort of guided couples experience.

Jamie Wheal: Wait, was that the [crosstalk 01:08:29] study or was that [inaudible 01:08:29]?

Julie Holland, MD: It was a MAPS study, but it wasn't [Midhoffer 01:08:31]. Anne Wagner, Candace Monson. I know. It kind of, it went a little under the radar, but it was published a few years ago. I can send Candace Monson and Anne Wagner are two of the women that I know are on the study. I'm blanking on the men's names. Go figure.

Jamie Wheal: That feels essential.

Julie Holland, MD: One of the things that did ... No, it's important. I mean, it's important and there will be eventually more studies like that, but it was definitely the first of its kind.

One of the things I did in good chemistry was I really tried to say their names, the women in the psychedelic research space, because the men seem very good at getting onto the documentaries and getting interviewed and the magazine. There are a lot of women in psychedelic research. You'd never know it. Everybody's Matt Johnson and Roland Griffiths and Rick and Steve Ross and all these guys, Michael [inaudible 01:09:27], Charlie Grove, they're lovely. I love them. They're all great. They're really great guys.

But the thing is that if you go to their labs, the people who are really doing the grunt work and the day to day work and writing the protocols and writing the papers and running the participants and doing all that stuff, they're the women right behind the men.

Jamie Wheal: The Masters and Johnson effect.

Julie Holland, MD: For Good Chemistry, I made a point of sort of interviewing a lot of women in the space who are doing really good work and aren't getting the face time.

Jamie Wheal: Rosalyn Watts in Imperial?

Julie Holland, MD: Rosalyn, right. Rosalyn Watts is in the book. Catherine McLean is in the book. This woman [inaudible 01:10:04] Dolan. I don't know if you heard her speech. She was at Horizons on Friday. Really interesting stuff about neuroplasticity.

The Neuroplastic Effects of Plant Medicines

Julie Holland: That reminds me, plasticogens, terrible word, plasticogens. Not good, but we [crosstalk].

Jamie Wheal: Is it a word? Is it actually?

Julie Holland, MD: Someone's trying to make it a word. There's certain words like entheogen and tactogen that may or may not make it. Plasticogens low on that list of words that's going to make it. But the idea is good. The idea is that there are certain medicines or drugs that induce a temporary neuroplastic state in the brain where the brain is more open to input and more impressionable.

I mean, again, I know I mentioned the Manson LSD thing sort of in ingest, but more impress means good and bad. In the right hands, more impressionable means I'm no longer going to wash my hands 30 times a day and worry about germs. I've made a decision. But it could also be for nefarious purposes.

For people who have got this sort of cognitive rigidity, whether it's anorexia nervosa and the thinking is no matter how much weight I lose, I'm still too fat, or being paranoid, maybe you have schizophrenia, or you're just delusional aboutor whatever. But fixed beliefs that are not accurate. Cognitive rigidity, this drug is good for me. I love of heroin. It feels good to me. I'm going to keep using it because it makes me feel better. It makes my life better. That's cognitive rigidity. You've got sort of misinformation that you're very tied into and that's how you're going to live your life.

It's a trans diagnostic phenomenon. What a medicine that increases plasticity does is it injects some flexibility into the cognitive rigidity and well, maybe it doesn't have to be this way. Well, what if you think about it another way? It's a chance for the brain to really do a little rewiring. I'm putting this in quotes. We know that the neurons, the brain cells make new sort of dendrites, sort of new arms. They make new synapses, which is new connections with other brain cells. We know that that ketamine MDMA, Psilocybin, LSD, Ibogaine, these things all increase plasticity in the brain for a certain period of time. It looks like, and Gould Dolan's research really strongly suggests that the shorter acting medicines open the window for a shorter period of time. You have something that Ibogaine where the experience could last up to 72 hours. Ibogaine is incredibly long psychedelic experience. The neuroplastic window looks like it may be open for as much as four weeks.

You take something like ketamine where it's really couple of hours, really short, neuroplastic windows only open a couple of days. The ones in the middle, MDMA, Psilocybin, they last four to six hours. The window lasts a couple of weeks. LSD lasted longer, window lasts maybe three weeks, somewhere between MDMA, psilocybin and Ibogaine. Shorter acting plasticogen, shorter window of neuroplasticity that you're working with.

But any neuroplasticity is good plasticity. Any rewiring, any rethinking, gee, maybe it could be a different way. I mean, those are the moments that you live for in psychotherapy where these aha moments where it could just as easily be this as that. Maybe I should look at it that way.

Jamie Wheal: That is important though. I think in your description, you're describing some therapeutic dialogue that could just be a rising in my own head, like, "Do I need to think this way," the same thing, but it almost sounds like you're presenting a therapeutic partner there to help the person navigate out of their muscle memory fixity into more expensive options or possibilities.

Julie Holland, MD: It would help. I think it would help and that's, but this is why it's so important that we make sure that the people doing this work don't have any nefarious ends in mind, because if somebody is in a plastic state, a suggestible state, an increased trusting and bonding state, they can be more easily taken advantage of.

One of the things I sort of got on the stage about at Horizons was that these are really serious breaches of trust and ethics, and we do need to air it out. We do need to talk about it. There's a lot of talk in the psychedelic community now about a few bad actors here and there. But the truth is, in therapy, the most common sort of bad outcome in regular psychotherapy is this interpersonal trauma from the therapist where there's some acting out boundary transgressions, whether it's sexual or just inappropriate friendships. I mean, you're really supposed to maintain a doctor-patient relationship or therapist-client relationship. In regular psychotherapy, there are a lot of boundary violations that lead to very bad outcomes. In psychedelic assisted therapy, we're going to have the same problem.

Jamie Wheal: Well, I think like Matt Johnson wrote that piece last year on, hey, don't smuggle in your worldview. If you're dealing with an impressionable patient and you're saying, "Oh, you've just had a soul birth or you've just contacted your star guardians or here's my Buddha, even just subtle micro new aging, vibing things are sort of as smuggling in of an ontology that may or may not be with full consent to the patient.

Then that recent obviously quite pronounced one on some of the west coast underground therapists where you're sort of like, "Oh, okay." So now we're in with the underground, you're obviously decoupled from many of the checks and balances of professional and credentialed work, but people are into this kind of no man's land between clinical psycho therapeutics within a medical therapeutic model within some sacred sacramental initiatory experience, and then maybe some psychosexual tantric thing, which could even just be advanced trauma work in integration, which almost always includes some of the sexual arousal circuitry that people are sort of making it up as they go. They're subject to their own shadows, blind spots, weaknesses, or even pathologies like scoutmasters and priests drawn to abusive children. Sometimes people are pulled into those spaces because of the power dynamics. Even if they came in with good intent, they might be bent by the power dynamics or the susceptibility.

Julie Holland, MD: Well, I don't know if you saw Laura Mae Northrup's talk at Horizons, but she was that in many of the people that she's interviewed who have been sort of victims of the psychedelic assisted therapy where there have been transgressions, a lot of those people have a history of being abused sexually in childhood, and that some of the traumatizers, therapists, also have a history of being abused sexually. There's just this chain of events that keeps happening. Her solution is that we have to focus on the healers. The healers need to be healed. The people doing this work need to do their own healing, or they need to get themselves healed because they're going to perpetuate this trauma onto other people.

The issue with the underground community and even above ground, we don't really have a certifying board. We don't have people who sit for their boards. There's no oral boards. As a doctor, I had to take so many different exams, licensing exams, relicensing exams, continuing medical education. You sit for your boards and it's like there's written boards, there's oral boards.

But the point is there is a mechanism for getting certified, staying certified, making sure that you're doing all the things you're supposed, to be a good doctor. We don't have anything like this yet for psychedelic-assisted therapists. There's no board certification program. There's no certification. Some people are going to be trained by MAPS. Some people are going to go to Fluence. Some people are going to get trained at Horizons, but like who decides you've had enough training, you haven't?

The Role of Mindfulness and Psychedelics in Accessing Parasympathetic States

Jamie Wheal: Well, I mean, there's two nerd questions, tech science questions that I'd love to ask you, I'll see if we have enough time for them. But I want to ask you one-

Julie Holland, MD: Okay.

Jamie Wheal: ... which is probably uniquely positioned to it. So in my researching of kind of the role of embodiment and specifically everything you described, they were just mouths with tubes and our souls are kind of primal one level. And that there is this spasmodic traumatic, both storing and dislodging of trauma. And that it seems to connect with brain stem activities, quite a bit of vagal nerve and endocannabinoid system. And if you look at the kind, if you go put them side by side, the endocannabinoid system and the vagal tone, or the vagal system, seem to do an awful lot of really similar things. They seem to be profoundly metronomic in the sense they set the rhythms of a bunch of things from inflammation to interception, to bone growth, to tissue growth, to cellular stuff, to hormonal stuff, to as you said, infant mother suckling, and impaired bonding, there's just an awful lot of overlap. And it's kind of gob something. Obviously, body keeps the score and Peter Levine, and some of that work is boosting, even your Porges' polyvagal might overstep the bounds of exactly everything the vagal nerve does. But-

Julie Holland, MD: Don't you say anything bad about Steven Porges.

Jamie Wheal: Okay. But, well-

Julie Holland, MD: Overstep what?

Jamie Wheal: But, I was with Lisa Feldman Barrett, and she's just kind of like, "Yeah, no that is a theory."

Julie Holland, MD: It is a big theory. Yeah. It's a point being exquisite theory, but it may and it may not be a hundred percent accurate. I mean, so, but your point is that the endocannabinoid system is everywhere you want to be when it comes to the parasympathetic vagal tone sort of thing.

Jamie Wheal: Yes. And what's the interrelationship between those two, because they sure feel like they're kind of they're-

Julie Holland, MD: They totally are. Yeah. I mean, when I think of the pharmacology of, fight or flight, that's like adrenaline, norepinephrine, epinephrine, and then, and cortisol, that's how I think of sympathetic, is like cortisol adrenaline. And then when I look at parasympathetic, I put the endocannabinoid system as the juice that runs the parasympathetic system. There's oxytocin, but how does oxytocin really get it done? Mostly through the endocannabinoid system. I also know that we are still, I won't say infancy, I'll say, look, we're in our adolescence about what we know about the endocannabinoid system. We're still figuring out extra receptors. They have CB1, CB2, and then a bunch of things that are vying to be CB3. And, there's more and more, I think that we're figuring out about the human endocannabinoid system. So, I do feel like it's the main thing that can put us in parasympathetic. Although, I would argue that opioids also do a pretty good job putting you in parasympathetic. So, and we've got our own great endorphin system.

Jamie Wheal: Oh, what of this, because obviously people tend to equate. And, my assumption is that many of the outlandish truth claims, if cannabis does all these amazing things for you, he was actually really saying the endocannabinoid system is powerful.

Julie Holland, MD: Right. It could even just be, you can substitute cannabis with parasympathetic. Whatever the parasympathetic system is, all the things that cannabis is saying it does, are really things that you would do if you were in parasympathetic. That your body would repair itself, that your inflammation would go, those are things that naturally happen in parasympathetic.

Jamie Wheal: Yeah.

Julie Holland, MD: And you're more open to social connections. Although, some people get pretty closed down with pot.

Jamie Wheal: Yeah. But, I mean that's right. There's growth hormone. There's stem cell growth. There's the anti-inflammation cytokine storm and TBIs, there's all sorts of explicit biomechanical stuff, but just what would be the top three, other than consuming cannabis to help prompt the endo... basically, endocannabinoids or anandamide in our system. So just so folks can hear.

Julie Holland, MD: So, I mean, anything that puts you in para, I think is going to end up priming the endocannabinoid system. So, the things that I tell people to do for para, just breathing in and out through your nose is already better than anything else. And if you can have a longer exhale than inhale, so breathing in for four and out for six, just through your nose that can help put you in para. Singing, chanting, talking about yourself, that's all going to be a long, slow exhale going to make you for feel a little better. But, the obvious things are like being held, cuddling, hugging, sex that isn't too sympathetic. If you can manage to have gentle sex. Because, usually sex is really combination of sympathetic and parasympathetic, and gas and breaks. But, eye contact laughing, that's a big one.

I think that the thing that I remember and that I said at the beginning of Horizons is that you really can't learn and integrate knowledge if you're in fight or flight. I mean obviously, when you're in fight or flight and there's really an emergency. You do have heightened awareness, but it's not a place of learning and integrating information. So, if laughing puts you in parasympathetic, then there really is something to be said for a comedy movie that has an important message. Because, you're going to be in parasympathetic. Yeah.

Jamie Wheal: The sphere of the movie thing is legit.

Julie Holland, MD: But you may actually integrate that information because you are very open to it because you're relaxed because laughter is disarming and a lot of breath work, I think can get you into parasympathetic. But the easiest thing is just exhale longer than inhale, in and out through your nose, better than anything, mouth breathing is usually fight or flight.

The Future of Delta Waves for State Shifts and Defragging Our Nervous System

Jamie Wheal: Yeah. And then, final ones, because this is my deepest genetic question, is the role and relationship of fundamentally Delta waves, brain stem reset. In kind of defragging our nervous systems and simultaneously providing some form of disembodied high information, high salience interior state. So, called [Dice Ross 01:30:46] work at Stanford, right where he's done the work with ketamine mice. And, I believe it's epileptic people and then, has been able to find that was a 3 Hz signal gone back without the ketamine and then re stimulated 3 Hz and prompt dissociative experience. And the dissociative state tends to have the antidepressant positive effects.

Julie Holland, MD: Yeah.

Jamie Wheal: So ketamine does it, the MIT anesthesiologist studies on nitrous oxide prompting double amplitude Delta wave states for 3 to 12 minutes until it normalizes back to her Bensons stuff at Harvard with the nitric oxide and brain stem research. You're like, "Okay, there is something really interesting-

Julie Holland, MD: Yeah, it is.

Jamie Wheal: And even shows up 5-MeO with the radar plots of cross hemispheric Delta wave activity at peak. And you're like, "Well, wait, we know that those states are massively meaningful, high salience, high significance, as far as the information and experience, the interior." We're also tracking that it seems to have something to do with almost flatlining our brainwaves down to super slow Delta. And we know that there's some interaction with deep brain stem kind of just hit the global system reboot. Which I'm imagining would allow we probably come back into a homeostatic, parasympathetic state of integration afterwards. So, back to your neuroplastic thing. So, it is that at least I've stuck my neck out saying, "I think this is arguably the kind of... This is the 21st century scientific protocol descriptor of what was likely involved." Not all every time, but most of these, in most ancient and esoteric death rebirth practices. How does that track for you?

Julie Holland, MD: It all tracks pretty well. I got a little distracted when you were talking about the three cycle per second. One of the things that got me really interested very early on in brainwaves was something called petit mal seizures, which are like Absence seizures.

Jamie Wheal: Yep.

Julie Holland, MD: Which is lights on nobody's home. Unlike the seizures where people are shaking or there's a tonic phase and a chronic phase to a grand mal seizures. So, these are not grand mal, they're small, they're petit mal. And the Absence, is just like, somebody's looking, but they're just like this, it's almost like you're in a daze, like lights on nobody's home. It turns out in those episodes, the entire brain is synchronized the three cycle per second and not just one area of the brain. And, I was just like, "That is so cool." So I'm very interested in this. It's like, that's an endogenous altered state where you're just not even really there.

It's like a very deep- I mean, when daydream, I don't want people to shake me out of a daydream. I love being in a daydream. I love that. I'm not, "What are you thinking about?" Nothing, not, I'm just like just for a minute, you just kind of zoned out. So, I don't know how that correlates with an altered state, but, I definitely buy into this idea that psychedelics have effects on brain waves and that whether you're in Delta or Theta, or what's happening with the drug experience, that is going to have an impact on what your experience is. And also whether, I would say whether you're in parasympathetic or not.

Jamie Wheal: Well, what do those folks report back when they come back from a petit mal, are they like, "Oh my gosh, you'll never believe it." Or is it just like what, like complete amnesia and no-?

Julie Holland, MD: Nothing

Jamie Wheal: Nothing.

Julie Holland, MD: Just nothing. What were you thinking? Nothing. I wasn't thinking it's-

Jamie Wheal: I wasn't even there. Is there awareness of self and passage of time or none of that either?

Julie Holland, MD:  I believe there is no awareness of self or passage of time in a petit mal. I mean, they call it Absence, because the person's just not there. Where did you go? Don't know. What did you think? I didn't. So, and that makes it very different, I think from these psychedelic experiences where we come back with a story like even 5-MeO where did you go? I don't know where I was, but there were these little people and there was this thing, you come back having been somewhere. You don't remember all of it, but you remember some of it. I mean, most people with a 5-MeO experience have a really weird story of, they don't just say my brain turned off. I don't know.

Jamie Wheal: No. You do not.

Julie Holland, MD: But I think, especially with this kernel headset now, I think we're just going to get more and more data about brainwaves and what correlates to what state. It is not my area of expertise at all.

Jamie Wheal: Mm-hmm (affirmative).

Julie Holland, MD: So, it all sounds very interesting to me and I'm curious about it, but I definitely don't have any pronouncements I would say about any EEG information whatsoever.

Jamie Wheal: But it does feel, I mean, all the trees we've been barking up. From-

Julie Holland, MD: Yeah.

Jamie Wheal: We've spoke about music. We've spoken about substances. We've spoken about respiration. We've spoke about embodiment, parasympathetic systems, role with trauma, role with peak states, neuroplasticity, both reworking our stories, but also our neural networks. It feels like we are in these early and interesting phases and you've been tracking this for your whole career, what is sort of an integrated model of human healing and becoming, and it's super interesting.

Julie Holland, MD: Yeah.

Jamie Wheal: Both the power and the possibility, but also just how early we are in that adventure.

Julie Holland, MD: I like that and I think that you can say that the whole psychedelic community is in that adolescent phase. We had a lot of fits and starts and the childhood back in the '60s and '70s, we're not where we want to be yet. We are really in this like, "Today I am a man." I'm like, "No, you're not a man. You're 13." Like that's kind of where we are right now, where... And, what's great about adolescence is it's really a time of tremendous neuroplasticity. And particularly you are exquisitely sensitive to social input in your adolescents. You really care about what your peers think of you. So, this is the time, if we are in our adolescence and this is a time of growth, and maybe being in that tragedy place of it's not all going to be roses, and chocolates, and bomb bonds. And, we do have some problems and we need to get through this awkward teenage pimple faced adolescence in our communities so that we can grow up to be big and strong.

Jamie Wheal: Beautiful. Well, Julie, thank you. And thank you for bringing the full package of you. The irreverent person, the woman's perspective, the academic and researcher, the practitioner, and even dare I say the activist, but thank you.

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