Dr. Jim Pfaus is a behavioral neuroscientist who has spent decades watching rats have sex to understand what's happening in the brain during desire, arousal, and orgasm.

I talk with Jim about what that research can teach us about our own desire, and just how much of it comes down to the brain rather than any one hormone. We tend to assume females have little say in when sex happens, but Jim's research shows the opposite in female rats.

They have complete control over whether it happens at all.

He also shares a study on partner preference: when a male rat has to wait for one specific female instead of getting instant, easy access to her, he'll seek her out over other females afterward. When there's no wait, that preference never forms.

We also get into what dopamine and serotonin are doing during arousal and orgasm, why SSRIs can shut down desire and what can sometimes be adjusted, and the real relationship between testosterone and estrogen in both men's and women's bodies.

Jim also explains what might be happening in the brain when GLP-1 medications affect libido, the inverted U-shaped curve behind arousal and performance, how early experiences condition what turns us on for life, why pain responses in conditions like PGAD and vestibulodynia are so hard to fully unlearn, and what his research suggests about psychedelics and sexual connection.

What You'll Learn:

• Why sex is a behavior generated by the brain, not just a matter of hormone levels.
• What decades of studying rat sexual behavior reveal about desire and consent, including how female rats have complete control over whether sex happens.
• Why male rats only form a preference for a specific partner when she isn't simply available on demand, and what that suggests about waiting and anticipation.
• How dopamine drives attention and wanting, and why it drops sharply after orgasm.
• What serotonin does to desire and orgasm on SSRIs, and how dosing can sometimes be adjusted.
• The real relationship between testosterone and estrogen in both men's and women's bodies.
• What might be happening neurologically when GLP-1 medications affect libido.
• The inverted U-shaped curve, and why some people need more stimulation while others need less.
• How early sexual experiences can condition lifelong arousal patterns.
• Why pain responses like PGAD and vestibulodynia are so difficult to fully unlearn, even after the physical cause is treated.

Get in touch with Jim:

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Get in Touch with Me:

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Preorder my book

Can I say that a different way? Hey y'all. Welcome back to another episode of Gyno Girl Presents Sex, Drugs, and Hormones. I'm Dr. Smeena Rahman, Gyno Girl. Today we're going deep into the brain, and we're also gonna go into a rat lab. My guest today is Dr. Jim Foss, a renowned behavioral neuroscientist who has spent decades studying the neurobology of sexual behavior, desire, arousal, reward, orgasm, and sexual learning.

Sure.

Hormones, neurotransmitters, much, much more, and even psychedelics. And yes, a lot of his research involves watching rats have sex. But what I love about Jim's work is that it challenges the simplistic notions and ideas about what sexual desire is and where it comes down to whether or not you have enough testosterone or estrogen or whether you're attracted to your partner. It is a be sex is a behavior generated by the brain.

And the brain is responding to hormones, dopamine, serotonin, reward, inhibition, sensory information, previous experiences, culture, everything. So we're gonna get into all of this. So welcome, Jim, to my my podcast.

Thanks for having me, Samita.

Yeah, I'm super excited. I'm gonna put all your details in the show notes because you have a very prolific sort of CV that everyone should know about you if they don't. But I always start with the first question, which is, you know, you know, I like a big good backstory, I'm Gaino Girl, so I wanna know like why you came into this field, how you came into this field, and why you're studying rats.

Thank you.

Well, okay. That's a th those are all big, big questions. and why I got into this field, I mean, I've always been interested in sex. I was interested in sex even as a kid, trying to know where babies came from. And it made no sense to me that the same place that I pee out of was some thing that actually sperm would come out of. And why was that? And why didn't I have it as a kid and what was gonna happen as an adult? But

All right.

Yeah.

Honestly, I mean to be honest with you, it was my first orgasm. That freaked me right out because you know something was happening, I didn't know what, and I put it off, put it off, put it off. And I think most men do this. Actually, probably most women do it too. Kinsey certainly found out there was a delay of you know, maybe a month when men would start masturbating to when they actually had their first orgasm. So there's something really scary about this. Your body is going.

Yeah.

taking you somewhere where you've never been before, you have no idea what it is. You anyway, I thought I was broken. My dad sort of, I I asked my dad about it, and he patted me on the back and said, Well, that's an orgasm. I said, what's that? He says, well, it's just something that happens during sex. And I was like, like, what is that? And that really started me on a quest. I mean, I was young, and that started me on a quest to try to figure out why did it feel good? Because all you could find, even when I became, you know,

Yeah.

was able to read Masters and Johnson like when I was 14, 15, it was a release of tension. And I'm like, what tension? Sexual tension. What's what's sexual tension? Like what are they even talking about? What is this release? And it really wasn't until 1981 when a paper came out in rats by an Israeli group who had found that whole brain bed endorphin when male rats ejaculated was through the roof.

Yeah.

Yeah.

And this was like endorphin. Wait a minute, that's that's opioid, that's a pleasure peptide. Like what the my god, now I figured it out, right? So I really kind of went in when I went to grad school to try to figure out how opioids are acting in both the male and female brain and what's going on there. What is it doing to dopamine? How is it interacting? And this was at a time when people were really beginning to study, you know, how opioids would sensitize dopamine and sensitize

Yeah, yeah.

you know, essentially dopamine as a as a attentional mechanism to cues that are associated with reward. And I remember thinking, that's really circular. But of course it's circular because that's how we think, you know, and especially, you know, we think we get rid of this egocentrism, but no, we always say, you make me feel this way, you make me feel good, you make me feel bad. And you know, to give that to a partner during sex.

In fact, it's your own brain and your own body that are making you feel good or bad, as the case may be. I mean, the partner might be inept or the partner might be totally like, you know, into your sexual landscape, but it's like regardless, it's your brain and your body and your interpretation of what's going on that's actually making that happen, making it be pleasurable or making it be less pleasurable, not pleasurable, you know. And I find that really intriguing that I was never able and nor

Are we able to really study this well in humans? Right. So, you know, I mean, I started out in a rat lab when I was an undergrad and I worked actually in NIH doing work on, you know, looking at delivery of drugs into the brain of rats. but it was it was really, you know, I thought about okay, what am I gonna do in my basement? Could I play guitar in a punk rock band in my basement, or should I follow that and not go to grad school? Or should I go to grad school because there's no way I can have a lab in my basement?

Yeah. No

But even then, the idea of studying this in people, everybody said, you know, well, we know everything. This is like, you know, in the early 1980s. Well, we know everything. Like there's nothing else to understand about sex. We, you know, the share the height report had come out. Everybody was like, wow, look at how wonderful we are with our sexual revolution, why we know everything. And then the pendulum during the Reagan era swung right back, right, to people not.

Yeah.

Yeah.

knowing anything and not wanting to know anything and having sex that that didn't tell you anything, say no to everything. Be afraid, be very afraid unless you're married. Right. And and I just want like to me it was a mystery how all this had come together and then fallen apart and come together and fallen apart. And so I realized that the way people were studying sex in humans was to study pictures.

Just say no to everything. Just say no to everything. Yeah.

You know, like the IAPS set of validated pictures, which, you know, nowadays nobody finds interesting at all. Like the porn pictures in IAPS are black and white. You can't really tell what's going on. There's like so much pubic hair. You don't know what's in what. And and it and it's interesting because students now say, my God, those are my parents.

Okay, and and they can't wrap their head around how anyone could have ever found those pictures sexually attractive or interesting or arousing or anything like that. So I think to understand human sexuality is best studied in humans, but I can't take brains out. I can't I mean I can I can take blood to analyze for hormones like prolactin, for example, after orgasm, but that's about the extent of it. I can't watch people have orgasms.

Yeah.

And if we do, if we put people like Barry Barry Kommissarek does in a magnet, right, and have them either have their partner stimulate them to orgasm or them stimulate themselves to orgasm, you're always fraught with problems with ethics committees where they are like I mean, Barry was lucky because he kind of put himself on the ethics committee and was the most conservative person on the ethics committee for like two years before he even proposed his project. So the committee would be like, Well, it's it's Barry and he's conservative.

Yeah. Yeah.

Yeah.

So clearly he's not going to do anything untoward. But, you know, I I tried to even get a prolactin pull from women who could give themselves orgasms without touching their genitals when I was back in Montreal. And it's like nobody would let me do it. Not my not my own ethics committee, not any of the four universities' ethics committees. They were like, my wow, you you women poking with, you know, taking blood after orgasm. you can't.

Yeah.

You does that mean you're gonna watch them have orgasms? And it was just this big conundrum. So this is really why I turned to rats, because I can watch them have sex. They don't mind me watching them have sex. I'm irrelevant as far as they're concerned. So it's much easier to do these neurochemical, neuroanatomical, and even molecular studies on them to try to find out, for example, when you've had certain sexual experiences, what genes are being activated, what genes are being unpacked.

Yeah, yeah.

You know, so you can look at the epigenetics of different kinds of sexual responses and different kinds of sexual learning. Yeah. So that's really why that was the that's the road.

Yeah, that's gr that's awesome.

Yeah. I mean what are you what are your some of the top things that you think as humans we could actually take a lesson from from ra from the rat from the rat population? There's so many, right?

my god. Well that's a that's actually the that's actually the topic of my book. right. I mean so the book's gonna be called, you know, sex lives of rats and what they and what they teach us about ourselves. And what's truly interesting is that yeah, well here's a here's a good example. Female rats, yeah, when they don't want to have sex, even though they're half the size of the male, if the male tries, they beat them up.

That's what I want you to talk a little bit about.

Mm.

Yeah.

Yeah.

There's no, they have any agency issue. They don't have a they have a their their bodily autonomy is complete 100% all the time. And if they want to have sex and the male isn't doing it, they'll even go to him and mount him and then hop in front of him, showing him what to do. I mean, dogs do this too, right? but I find

Yeah.

Yeah. They don't have government regulating their sexual reproductive. Right.

No, they don't have government regulating anything. I mean, I had I had the author, the author Naomi Wolf in my lab like 15 years ago because she had had a problem with her spinal cord, she was losing all her sensation in her clitoris, she didn't know why. And people were telling her, even G OBINs were telling her, It's early menopause. Deal with it, right? You don't have sensation anymore. Well, you know, you're not gonna make babies anymore either, so

Mm. Yeah. Yeah.

Who cares? Right? Learn to learn to play bridge. Abject dismissal. And then she was at a party and she said some doctor noticed a slight curve in her spinal, in her in her spine, and just the way she was standing. And he asked her, and she had had spina vivid as a kid. He said, Well, I mean, I wonder you need to get an MRI. You need to s get a spinal MRI and see if, you know, see if there's any kind of nerve crush going on. And sure enough, there was.

Huh, yeah. Dismissal.

Yeah.

Yeah.

Yeah.

Right where the prudental was entering, right? And so she got it fixed and all of a sudden her sensation came back. Now, for somebody who is a dyed-in-the-wall social constructionist and there is no biology, and you know, there's no, you know, all this, you know, kind of biological determinism is wrong and everything is socially constructed. This was a revelation for her. And she wanted to know why this had happened, why this works, right?

Yeah. Yeah. Yeah.

So she's in my lab and she's watching the rats are doing. And one male rat had had like five ejaculations. He was done, but the female wasn't done. So she actually hopped out of the cage that she was in, this big bilevel chamber. She actually jumped like, you know, three times her height to get over to another chamber where the male was still copulating. And and she looked at this and said, She just, she just took it. Okay. And I remember.

Like I didn't thought about this before, but the words that came out of my mouth were exactly this. I said, Well, of course she did. And they were What do you mean, of course? And I said, Well, she didn't grow up in a culture that slut shamed her for having desire. This is real female desire. You want to know what female desire is, here it is. Right. So there's no I mean, her autonomy is complete. And the females are the ones who initiate and control everything.

Yeah.

Yeah.

Yeah.

Yeah, yeah.

You know, and as much as you know, the patriarchy can say, well, we're in control because we're the big strong men. No, no, no. It's like yay or nay. And if it's nay, they ain't nothing you're gonna do to make it yay. It's just not gonna happen. There's no yeah, it's it's well, it's already tipped in the other direction. Yeah, it's like you're not gonna untip that, right? And I think I think we don't realize that. Like we like to kid ourselves thinking that we have some

There's no sexual tipping point.

It's already tipped. It's not gonna untip.

degree of control. I mean, yeah, it meets 50-50, but still it's like I mean, the gatekeepers are not men. And they're not men in other species, but other species don't even think about it. It's not, there's no political issue, there's no socialization issue. Female rats want what they want when they want it, and they don't want what they don't want when they don't want it, and there's no in-between. And I find that really intriguing. So that's one thing. If we could be more like them,

Yeah.

Yeah.

we wouldn't have a problem, right? I mean another thing, another thing we learned was that, okay, so so alcohol, disinhibition, right? By 1977, alcohol researcher, very famous one, Terry Wilson, said that, well, you know, you can't study disinhibition in animals because they lack the cognitive capacity and cognitive control of sexual behavior that that humans have. Okay. And every, you know,

Yeah. Too bad society gets in the way of it. Right. Culture and social.

Uh-huh.

You you you get this I mean I get this in my psych classes all the time. Rats aren't people. Why are you studying rats? Like what has that got to do with psychology? Well, turns out you have to train male rats to be inhibited. And we gave them sequential access to sexually receptive females, then non-receptive females, then receptive, then non-receptive. And over time, it took about five trials for all the males' attempted mounts to go down to zero.

Yeah.

Okay, so they knew when they were with a non-receptive female, don't even try because A, yes, she will beat you up and bite you. And B, you're still not going to get anything out of it. So, you know, I mean the males in the first trials would would suck. They would actually kind of go off in the corner and look away from the female and you know, my god, they had like little temper tantrums. It was really funny. It was really funny. And then they just donated it. So now they make they learn to differentiate. We give them alcohol in the inhibitory condition.

wow.

And we get this amazing disinhibition where now they're trying to mount her. They're even ejaculating, despite the fact that they get no vaginal penetration whatsoever. So they're getting fraudage, so like rubbing their erect penis against her backside, but nothing's going in anywhere because she's not holding a lower dosis crouch. So but the same dose inhibits when they're with the receptive female. So isn't that interesting?

interesting. Huh. Yeah.

Right, that the alcohol can disinhibit, but inhibition has to be there present, has to be there before you you ever get disinhibition. And you go back into literature, and people have talked about this for hundreds of years, right? You know, you wanna, you know, the right one, if you want to apply alcohol to a person, don't get somebody who's uninhibited, get somebody who's inhibited. Then the alcohol will disinhibit and you can manipulate that into

Yeah.

You know, into sexual activity, but it's like the one who's not inhibited, alcohol is just gonna give you drunken sex, which is not gonna be fun.

Right. Yeah, that's true. Yeah. that's so interesting. Yeah, so it's more than than than mitzai, I guess, in that respect. Tell me a little bit about what our understanding around dopamine too. I was thinking about this, that sometimes I feel like, you know, we think about dopamine, we think about the pleasure pathway, we think about its wanting and liking. Can you like take us inside the brain of an animal to see

Yeah.

That sees a potential partner, like what's happening? Is there a sexual stimulus all the time? Where's dopamine come into that play? How does that work out?

Mm.

Well, that's coming in early on. I mean, we think of when you think of dopamine, just think of a petitive be you know, when you want something and you're gonna go get it, dopamine is the energizer of that. It's not necessarily the energizer of pleasure, it's the energizer of attention and kind of movement towards something that you're interested in. So you see someone who's attractive, you attend. So you look at that person, you make eye contact, you do things that might resemble, you know, synchrony.

Yeah.

Right.

with that individual, that's all dopamine acting, right? And opioids are are being released bit by bit by bit. The closer you get, the more reward it you feel from that. But what's interesting is that dopamine by mediating attention and movement toward things that you like or away from things you don't like, once you have an orgasm, dopamine, because of the opioid release and the serotonin release,

Dopamine plummets. Boom. It goes way down. Okay? Now it's different for different people, obviously, but what's interesting in rats, at least in male rats, it the downtime is actually the time that the male is refractory. So decreased dopamine actually produces a refractory period. And now we find when we do clitoral stimulation with a paintbrush in females, yeah, they have a little downtime too. Male rats downtime can be five minutes.

interesting.

Female rats downtime can be like 30 seconds, right? And then they're back for more. And they have another little ratty orgasm. Dopamine goes down. It's down a little bit longer each time, like it is in male rats. But the timing is much shorter in females than it is in males. So we could look at females and say, gee, you have multiple orgasms. Well, males do too. Male rats do as well, but they don't have nearly as many. So there's much more inhibition in that brain.

Mm. Yeah.

Okay.

Then then

So you think someone that has more of a dop like response with dopamine is more likely to have sort of more orgasms as well? Yeah.

Probably. I I would think so. And of course, orgasm is a sympathetic event, right? So so and dopamine and noradrenaline are drivers of sympathetic outflow. Yeah. So probably the more you have that now. On the other hand, you know, if you're doing tantra, you might actually wait it out. You might edge. And what's happening to dopamine when I mean animals don't edge, they just do what they do. But what's happening to dopamine when you edge?

All right.

Yeah, yeah.

Right.

is a really interesting thing because probably you're making it go up and down and up and down and up and down and up and down until you let until you actually let it happen. Right. And then of course the opioid release is much greater under those circumstances, right? And and we found a similar kind of thing in rats where if males and females have to wait, and it's a very easy to impose that by putting a divider in that only the female can go across.

Let it happen, right?

yeah, yeah, yeah, yeah.

Uh-huh.

Right, so the male actually has to wait. And if there's only one hole, he has to really seriously wait for her to come back. And she'll come back, get a vaginal penetration, leave, come back, get a vaginal penetration, leave. And the male, of course, you know, he follows her. He wants to get close. Sometimes he gets his head stuck in the hole. It's it's pretty funny. You gotta he really has to learn. And he also shows this begging posture, which is really interesting. But he has to learn. Now, under those circumstances, when they have to wait.

That's when we generate partner preference. Okay? Which we don't if it's too easy. So if instead of one hole, you have four holes. So the female can go in and out, in and out, in and out, in and out. There's no waiting. It's like swiping left or swiping right. There's no waiting. Off you go. Bip, bif, ma'am, thank you, ma'am. You're done. And they don't learn a partner preference. But it turns out that the opioid effect when you wait is much greater.

Mm-hmm, mm-hmm.

Right.

Yeah.

And activates a s activates not only a serotonin activity, but also activates oxytocin much more.

That's so interesting. Because you think about how, you know, with all of our technology and our you know, we have our phones in our hand and the technoference that happens with sexual relationships, like how, you know, of those dopamine hits that people get by, you know, doing whatever scrolling they're doing or whatever, that how it then would down the downstream would have such an impact on their sexual function.

Sure, sure. And and because it's so immediate. And even rats like it when it's immediate, right? But but they don't learn very much from when it's immediate. Right. So it's it's always this weird balance between, well, you know, if you have to wait I mean, think about our ancestors who had to write letters, you know, and had to travel, you know, long distances to go court one another. It's like this involved a lot of waiting.

So I mean yeah.

Right. Yeah.

Yeah, that's true. Yeah.

Yeah.

You know, and you didn't get this immediate, you know, I sent a letter. I know I'm gonna have to wait now a week before I get a letter back. So all that anticipation is massive, is massive dopamine release. Right? I mean it's yeah.

Yeah.

Yeah.

That's amazing. Yeah, that's so interesting. Simpler times could have been better better for sex, maybe. Maybe, you know. So when we talk about dopamine, you know I always think about serotonin. I think about, you know, patients I have who are SSRIs and, you know, maybe their anxiety's better, depression's better, but they don't want sex anymore, they can't have orgasms.

Yeah, maybe.

Mm-hmm.

What do we think serotonin is doing to the sexual response? Is it suppressing desire? Is it mitigating dopamine? Is it affecting general response? Is it doing all of that? What do you what do you think from a scientific?

It's do it it's it's doing all of that. I mean the in nineteen sixty-four there was a paper put out by a Swedish pharmacologist, Bank Meyerson, who basically talked about dopamine and serotonin always being at war with each other in the brain, everywhere they look, from the striatum to the nucleosacumbens, right, part of the reward center, but also in the f in the frontal lobe, right? And now we know at the level of the spinal cord, there's

Uh-huh.

If serotonin is up, dopamine is down. If dopamine goes up, serotonin goes down. And at the level of the prefrontal cortex, which is where your executive function comes from, that's really the I mean, if you think about it, serotonin up, you've got a lot of inhibition going on. And that inhibition, behavioral inhibition, is part of what you get with SSRI treatment. It's a good thing because it's going to inhibit depression, it's going to inhibit.

Yeah.

Yeah.

anxiety. So hopefully these are things that aren't gonna aren't gonna be things that that the dopamine system has to focus on. Now when dopamine's up and serotonin's down, you have a br in the frontal lobe, you have a brain that can't show executive function. You have a brain that you know is likely to spend your savings, okay? And is likely to do more drugs and is likely to do all sorts of things that are

Yeah, yeah.

impetuous that are that you might think would have some kind of you know impulse control problem and the impulse control problem is because dopamine's up and it's inhibiting serotonin you need this balance between the two to be able to you know learn how to play piano you need it to learn how to throw a football or kick a soccer ball or drive a car or ski or do anything you need that balance between the two so that

Yeah.

when one goes up and the other goes down, it doesn't plummet. Right? Well, at the level of spinal cord, that's also true. Serotonin helps to regulate the parasympathetic tone. So once the blood is in the genitals, it's in the clitoris, it's in the labi, it's in the penis, whatever, serotonin helps keep it there. Okay? So serotonin is activating parasympathetic arousal. Orgasm activates sympathetic arousal. So

Yeah, yeah.

You have a whole network, a system there where you gotta disinhibit the so you gotta inhibit the serotonin, which then disinhibits the sympathetic outflow, now allows you to have an orgasm, but then allows blood to move back into the core from the periphery. And you know, again, if you're taking an SSRI, it's acting systemically at all these levels at the same time. Right? So, you know, arousal issues occur, desire issues occur, but

And no orgasm happens as well, if depending on the SSRI. So no notice it's really interesting. So here's your here's your dose of fluoxetine. You give a dose of bupropriate, right? Which is of course a it's an DNRI, it's a dopamine and adrenaline reuptake inhibitor. So now there's going to be more dopamine and noradrenaline, but give a quarter of the dose, not a full dose, give a quarter, okay? Reduce this by a little, and sure enough.

Yeah.

Mm.

People can have their orgasms back in addition to still getting their depression and anxiety and OCD treated. Right. So it's a it again, it's this balancing act between the two. And everybody's different. Right. That's right. That's right. Right. So it's a so you know, when it's there, people need to understand the system and how it works to be able to tighter the and tweak the doses properly. Yeah.

Exactly. Yeah.

Right, because not everybody on SSRIs have these problems.

To tweak it.

And it's interesting what you said about how serotonin keeps the blood and the genitals and all the things. Because I think about my PGAD patients who come off of SSRIs too quickly, or you know, sometimes I know it's from region five because, you know, they came off of that medication so quick, or they didn't, you know, you know, one of the medications they were more sensitive to, and because of it, they developed or got into this PGA cycle, you know.

Absolutely. Absolutely. Well, you know, and you think about it, if serotonin has been keeping dopamine down and tolerance occurs, a withdrawal effect from that is going to be dopamine's now up, up, up, up, up. And one of the things dopamine in a region of the little bit in front of the hypothalamus called the medial preoptic area does is it it essentially sends the signals t to increase or to make it feel like you've increased.

Yeah.

genital blood flow. Right. So if you if you knock dopamine in this MPOA out, not knock it out completely, but you reduce it or take over, take it over, like a drug like varenoclein does or zolpidem, like both of those end up treating the PGAD feelings of the the feelings of PGAD. They're not, you know, if you still have a tarylov cyst, you have a taryl of cyst. You need to get that, you want to get the PGAD removed, you got to remove the cyst, right? But

Yes.

Yeah.

Yeah.

Dr. Sameena Rahman (27:29.492)

You have to you have to look at all the regions, right.

This some not somehow, it by knocking that out, the brain is no longer telling itself, I feel engorged, I feel engorged, I feel engorged. Despite the fact that down the spinal cord, you still have this tarlov cyst that's irritating the nerve. So that's going up to the brain, but now boom, you've got like the Great Wall of China here that's knocked out the system that says, I'm aroused? Okay, here's blood, right?

Yeah, yeah.

Right. Yeah.

Yeah.

So that system isn't knocked out because that system also tells the frontal lobe what you're feeling. So yeah. So it's a really interesting neural circuit.

Yeah, yeah, that's real cool. Well, tell me tell me what you think about how the you know, we have those case reports of people taking GLP ones and you know, there's some people and as happened to for a few of my patients too, who I think that the signal for their PAD, their persistent genital arousal, is coming from the brain. And, you know, of course we treat the pelvic floor, of course we look at region one and you know, we rule out spinal stuff. But like, you know, I've done this with some patients who like

Right.

Remove parametopausal, they had some weight gain. Well let's see what happens when you go on a GLP one and their PGAT symptoms come down, right? Because you're the same way I think it's, you know, reducing that food noise and reducing all the dopaminergic response. Where how do you think that like scientifically works? Is it attenuating your dopaminergic response or what do you think?

Well, it's probably it yes, it is. And it's attenuating even the response of to food in regions like the nucleus accumbents when people are very food driven. Okay. And and food driven for many different reasons. It can also be because the flavor of food is really good and things are high sugar, high starch, and we tend to like high sugar and high starch, even though it dysregulates us. GLP one is reducing that. Now what's interesting.

Yeah.

Right.

In the hypothalamus, everything that reduces food intake stimulates sexual desire and orgasm. And it and it does so by this diff by this regulate by this regulation. In the nucleus accumbens, though, a Q for food and a Q for sex drive dopamine. So it's this driving is in different regions, and the GLP is likely doing this in the hypothalamus and not.

in these other regions and then the output of that is what's shutting down or reducing the dopaminergic tone. Right? So but but everything like like the melanocortins, right? They're there's a good one like like like Bremelanotide or Vilezi now it's called right in the hypothalamus melanocortons inhibit feeding and they facilitate sex. Where

So yeah. Huh.

Mm-hmm.

Other things like ghrelin, which activates feeding, inhibits sex. Because I I think you know, despite the edible panties back in the nineteen seventies and eighties, you you actually can't eat while you're having sex. Peop people don't do animals don't do this. They they regulate it. They eat after, right? But they, you know, it's not like and even if they have the ability to timeshare, and people have done these studies. Well, here's food.

Mm-hmm.

Ha ha

Right. Yeah.

Yeah. Yeah. Yeah.

Here's a receptive partner. What are you gonna do? They'll go for the receptive partner first. And then and then male rats, when they after they've had like three or four ejaculations, so now you've got more inhibition on the sexual system, then they start going and nibbling. Right? And f female rats too. It's like once they get pregnant, they immediately go into the burrow, they start making their nest, and they start hoarding food and eating food, because you know, this little mutant is gonna be.

And then

basically taking over 40% of their of their metabolism, right? So you need to eat when this happens, right? so yeah, so it's a it's an interesting thing, but then you have people that say, well wait a minute, I have a patient who experienced a decline in desire and a and a decline in in orgasm capability. This is really interesting. So there's a principle. It's called the inverted U-shaped curve.

Right, right.

A hundred percent, yeah.

Yes. I was gonna talk to you about that. Yeah. Yeah.

Right. And we've heard about this, you know about it's an optimality curve, right? The original one from 1909 was the arousal performance curve. Okay, so as a as per as arousal goes up, performance goes up. It reaches optimality at some level of arousal. But then as arousal continues to go, performance goes down because you can't focus, you're too nervous, you're whatever it is, right?

Uh-huh.

Yeah. Right.

So there's an optimal amount of arousal that leads to an optimal amount of performance, right? And you can draw your line over to optimality. People's response to drugs, their response to cues follows the same pattern, right? So, and we could think of reward following the same pattern too, right? When things are too rewarding, it's too much. When things are not rewarding enough, it's too little. So there's an optimal amount of reward that you want.

Right. Yeah. Yeah.

For certain things. If the food tastes too much, now that's hard to understand that, but imagine that the a flavor would be too robust in your mouth, right? It would actually hurt and probably would turn on pain. And you know, Barry Commissark has tried has talked about this idea that you know you need you need excitation and inhibition together to stop genital stimulation from being aversive.

Robust.

Right. Yeah.

Right. Right. It could be painful, yeah.

Because it could very well be aversive. And it af after you've had an orgasm, it can be if somebody continues, you know, Mr. Snake tongue continues being snake tongue. It's like you whoa, whoa, whoa, wait a minute. I need a little bit of time to calm down. Just just whoa, Sparky, wait a minute, cuddle with me for 30 seconds and I'll be back. Right? But you know, you need that downtime because it's too aver it's it's aversive. Yeah, it's too much, right? And I mean the same thing goes with the penis. If somebody's

Right.

Yeah, yeah.

It's it becomes painful, yeah.

continuing to manipulate and stimulate, especially the glands, after you've ejaculated, it's way too much. It's just way, you know, so whoa, whoa, whoa, whoa, whoa, wait a minute. Okay. So that inhibition has to, you know, it's going to override that and then come back down so that you can experience it again and go up and come back down. It's very natural for that to happen. And I think that when these things are happening to people, some people have too much inhibition.

Yeah.

Some people have too little. And so that's going to define how this curve works. So for some, you know, this may be where the curve is for me. And for somebody, the curve may be over here. It's still the same curve, but for them, even the hint of vanilla is enough to it is too much, right? So and and for somebody over here, right? Well, they may need way more stimulation to get things going.

Too much. Too much I'm done. Yeah.

Yes, yes.

Right. And so, you know, spanking, p hair pulling, something of that nature, or even drugs, right? Drugs that stimulate the system, like cocaine, for example. So this person may tell you, my god, the sex I had on cocaine was amazing. And and when this per of course, me neither, but this person who who hears it might try, and for this person, it's a dysfunction.

I'm not advocating for that. Yeah.

Whereas for this person it's something that makes them come alive.

That's why in medicine we really look for nuance, right? Not there's not a once that everyone tries to make everything in women's health and sexual health algorithmic. And it simply is not that way, right? We can't algorithm our way into treating patients. This is and and with the GLPs, what I tell patients when I tell them, you know, I want to address how you might feel and what's your sexual response could be changing, you know, I and maybe it's simplistic, but I'm like, I'll ask my you know, because I only treat women, do do you find sex rewarding?

Right. No, that's right.

And you know, most of my midlife patients are gonna say no. So I'm like, Well, your sexual function may not be affected by this medication, right? But if you do find it very rewarding, then your reward pathway is gonna be right. Do you think that's a r I mean that's kinda how I explain it to

Mm-hmm. Yeah.

Exactly.

Right. I I but I I think that's true. And I again I think the sensitivity is such I mean and this is not static. This is how you might be when you're a teenager and this is how you might be when you're older, right? 'Cause because the sensitivities change with age, right? And so and people just have to understand that that if this shifts, it doesn't mean you're weird, it doesn't mean you're not functional.

Yeah.

Yeah.

It just means you might need a little bit more stimulation in order to in order just to generate the arousal. And so, you know, you see people that have turned to porn to do it, that turn to kink to do it, and and they're just like, well, I don't know what's wrong with me. I didn't used to be that way. And it's like, there's nothing wrong with you. You just need a little more. Right? And

Yeah.

And you know, people's in you know, physiology change, they get diabetes, they get, you know, blood pressure issues, vascular issues, all these things that affect your arousal, you know, that's why we say sexual health is health, right? 'Cause it's the first indicator of so much so much of a bigger picture that might be happening. Yeah.

Yep, yep. Exactly.

That's that's absolutely right. Yeah. So

You know, Jim, what I I enjoyed another lecture you gave at Ishwish and you know, this is so timely because just yesterday, I don't know if you caught it in the news that the FDA had this meeting about testosterone for women, where there was a big discussion around, you know, like the research and why we need to be able to like, you know, deregulate it and why we need to

you know, offer women government approved testosterone. And so, you know, a lot of our Ishwish colleagues were there, Rachel and and Jim. but you know, and you get a you gave a great lecture, I think it was last year at Ishwish when we talked about the estrogen testosterone tango and how, you know, we're very simplistic when we think about some of these things, right? Like testosterone, low testosterone, it must be your libido. Can we talk can you talk to

Yeah, yeah.

Right, right.

you know, like in a simplistic way where our listeners can understand some of the big take-home points I think that you made from that lecture and how it's not, you know, that these that, you know, testosterone really, okay, yes, it's for sexual function, but it has a bigger picture that there's more to testosterone than just sex. And the same with estrogen, like there's more to estrogen than, you know, reproductive. We we know that. But I I liked how you kind of like went into that during that lecture. Can you kind of talk to the audience about that?

Mm-hmm.

Well, there's there's a lot of overlap between the two, right? I mean, you know, and and they work on similar systems. Here's a good example. Estradiol can activate the rate limiting enzyme that makes dopamine. So with estrogen, with estrogen z binding to the estrogen receptor, you're gonna make more dopamine. Okay? Doesn't mean you're gonna release it, but you're gonna make more.

Mm-hmm.

With test so that's the first punch. The second punch is testosterone. And of course, you think over the cycle, estradiol goes up, then it begins to go down, testosterone goes up, and actually goes up quite a bit, right, from the ovaries, and then and then comes down, and then the corporal lutea, once you release the egg, starts to secrete progesterone, so you're getting progesterone all toward the end of the cycle. Now, what's the estrogen and testosterone doing? Well, the testosterone is activating.

It's cycle, yeah.

Genes that make proteins that facilitate release. Like nitric oxide synthase that makes nitric oxide that then facilitates it. So the one-two punch is that estradiol makes more dopamine, and testosterone comes along and makes you more likely to release it in the presence of a cue that you find attractive and interesting. Okay? And that's just the two of them working together. Testosterone, of course, in the brain.

Mm-hmm. Right.

Huh, yeah.

Can be converted by the aromatase enzyme system into estradiol. And the one thing I pointed out in that talk was that you know, everybody thinks, testosterone is blue and estradiol is pink because women have estradiol and men have testosterone. Women have testosterone too, they just don't have a steady state of testosterone. Over the cycle, it cycles mid, it goes up mid-cycle, okay, around the time of ovulation.

Yes.

Yeah. Right.

Right.

Yeah. Right.

For men, yeah, we have steady state, relatively steady state. I mean, we have more in the day and less at night. We have relatively steady state testosterone, but our brains are acting like big ovaries, which are taking the testosterone that we secrete and converting it in very important brain regions into estradiol. Okay? So the the idea that men should be afraid of estradiol because, my God, it's going to give me breasts.

Yeah.

And it's gonna give me, you know, it's gonna, it's gonna take my penis and turn it into a vagina. It's like, no, it's it's not gonna do any of that. What it's gonna do, very similar to estradiol, it's gonna help with osteoporosis, it's gonna help with all these things. And so, but testosterone is anabolic. So, as an anabolic androgen, it becomes a scheduled drug as far as the FDA.

Yeah, yeah.

Right.

Yeah.

And yeah.

and the d and the DEA are concerned in the US, right? Because men will take it and stack on steroids, stack on those steroids, androgenic steroids, to bulk up. Because it does help put muscle onto so women are taking it too to bulk up. One thing that happens though, interestingly enough, is that because women only have this at a one time during the period, and they don't have it at these other times,

You don't get the negative feedback. So women will have increased size of clitor of their clitoris, for example, who are taking testosterone, a lot of testosterone, not a little bit that you might take to amputate, but a super physiological dose. Whereas for men, it does the opposite, right? I mean, you know, again, it's the inverted U-shaped curve. We're we're starting out here. So our more testosterone because of negative feedback.

Yeah, yeah.

Right, that's super physiologic, yeah. Yep.

It's like sweet. yes. Yeah.

Is now shutting down the ability of dihydrotestosterone to function, and your penis starts to look like you're pinky, right? And you know, you see this in men that work out. It's like they get atrophy, but the atrophy is because your testes are no longer making dihydrotestosterone, which is keeping the genital tissue normal, right? So you we get shrink you get shrinkage. Whereas women get increased size, right?

Yeah. Yeah.

Right, right. Yeah. Yes.

What you know, which is it which is very interesting. So they said, Well, why does that happen to women? Well, 'cause women are not up here with steady state as men are, right? Because women are lunar. You know, right? Our whole everything is yeah. So they work together, they can work differently depending on sex. And when they work together, they're not only working on the sexual system, but they're working on the body to maintain muscle mass, to maintain muscle.

Yes, yeah, yeah, yeah.

to fat ratios, to maintain bone, to maintain all this. I mean, honestly, I fully intend to go on testosterone and estradiol when I get much older to just maintain my body. You know, and and and the doses don't have to be this huge dose that gives you, you know, gynecomastia, for example. You don't, you're not going to get gynecomastia by I I mean, I know people that worked with rats who were injecting estradiol, and I I remember this one guy

Who inadvertently pierced his finger while he was injecting females with S with estrogen, and he f completely freaked out. It's like he thought this one, I mean, there was no estrogen that it went into his system, but he was completely freaked out that he was gonna turn into a woman. And it's like, it's like, dude, that's not gonna happen. Like, calm down, you're okay, right? But we have these preset ideas about, you know, females are estrogenic and males are.

Androgenic and okay, the names come from that, but it's not that way. They work in our bodies and our brains convert. In fact, without estradiol, yeah, my my brain and body would never have had a male phenotype because it's the conversion of testosterone to estradiol that actually masculinizes the brain and masculinizes the body. So it's like it's like we need estradiol. Estradiol is

Right. Yeah. You need yes.

Just as manly as testosterone is. And yeah.

Yes, yes. And a postmenopausal woman has less estrogen than her partner probably. So

Well, certainly in the brain, that's that's true. And that's and that's why hormone replacement then becomes a really important issue for people for whose hormone levels have gone down. Right? Because that's shi in that u inverted U-shaped curve, that's now shifting them from here, boom, down to down to less. And you go down to less, well now you want to go back up, right? Yeah.

I mean in right. Yeah.

Yeah.

Yeah, yeah, no, that's true too. do you think I know you've done a lot of work on, you know, can we learn what turns us on overall? Like is this something that you know how does someone who's sexually neutral become more sexually salient in that respect? so I guess I wanna know what you've learned. What w what are these like the experiments that you've done learn about our fundamental capacity for our brain?

To learn what turns us on.

Well again, rats don't live in the culture that says, well, that shouldn't turn you on. You shouldn't be turned on by that. it's very easy to pair something, you know, that's neutral with sexual reward and get them to focus and twig on that and make them think that they need to have that for them to become aroused, right? So we did a s we did a study with a little tethering jacket that we had put on the males and

Right.

Yeah.

Right.

Mm-hmm.

Sure enough, once the males in their early sexual experience had associated that with their orgasm, now you take the jacket off and it's like, Where's my jacket? I need my jacket. I can't here's the female. I might mount her a couple of times, but I need my jacket on in order to have my full experience, right? So it's it's a I mean, they looked as if I'd given them fluoxetine. It was really interesting, right? So they just had a big, huge, massive delay.

interesting. Yeah.

The the ones that ejaculated had a massive delay. Most of them didn't, because now this little jacket, which is i it's not like a leather jacket. It's not got studs and all. So it's a it's a stupid little shell jacket that's got, you know, a thing that attaches a ring on the back. But it's like they couldn't generate arousal without without the jacket on, right? And and I mean this lasted all their lives.

It's not Yeah. Like the

Interesting. Yeah.

Yeah.

So it's a it's a so first experiences are really important for this. And I think they're important in humans as well. We don't think about it, you know. So, but I I like I've known people whose first sexual experiences, you know, older people than you and you and I, whose first sexual experiences were like in the backseat of a 57 Chevy. Okay. Okay, well, what the back seats were were leather, and the smell of that leather was very peculiar. And people are like

Yeah, yeah.

Yeah, there's something about the smell of that leather. I don't know what it is, but it really turns me on. And you're like, well, what it is is that you had your first experiences with that, right? So it it has become very naturally a salient cue for you. It hasn't necessarily become a fetish, but it can in individuals that are more sensitive to that. Right? And I I mean it's a perfectly natural thing. We probably are attracted to people with the same mechanisms.

Associated with it, yep.

Right.

Right.

Right, that is the first people that you masturbate and fantasize about, the hair color of these people, maybe the the chin dimple, whatever it is, right? It becomes a thing that you know now begins to focus you. Yeah. And it activates your dopamine and focuses, you know, out of an array of possibilities that are out there. Things pop out, things pop out at you, right? And we call that a gestalt, but the gestalt is what pops out at you, right?

Whatever that's the

That's what you associate. Yep.

Yeah. Yeah, yeah.

Is the thing that's more salient. So the good thing is that's what keeps diversity in our species. That's why we all don't look the same. Right? You know, we look we look different because of this level of early experience being essentially chaotic. Right? Because, you know, I mean, I mean, Bem wrote about the idea that exotic becomes erotic.

Yes.

That's true. Yeah. Yeah.

Yeah.

Okay, and how does that work, right? But it works because when you've done something with somebody absolutely brand new, like doesn't look like anybody you've ever been with before. If the sex is good, you're gonna start to say, my god, I've never I mean I've never had a blonde before, but now I think I like blondes better. Okay, why? Because the sex is better. Why was the sex better? Just because the association, yeah.

Right.

Yeah. Your association, yeah.

That's so interesting. And in the same respect, I feel like I'm thinking of my patients who have like, you know, lifelong vestibulodenia, they're in pain the whole time. Like say they have, you know, congenital under a proliferative, we remove their vulva or vestibule. We think this is gonna be the solution. They get the pelvic floor PT after. But I think, you know, what becomes so hard and why they so many times have to go through so much therapy and EMDR or whatever, is that pain association is always there, right?

Mm.

Mm-hmm.

And so I I can actually literally show a patient, like, look, your vestibule is not there. Remember that was where I and they say, Yeah, it doesn't hurt when you touch me. But when they go into a sexual encounter, boom, they can't do it. Like and this happens and and for some people, you know, something like an EMDR might work, but I still struggle to like can we unlearn that response is the question really.

Yep, yep.

You're never gonna unlearn it. All you're gonna do is suppress it. Right? So, so I mean, we find the same thing in female rats. We very serendipitously, so when we were doing clitoral stimulation, we were using a number four camel hair paintbrush, which is really beautifully smooth and very soft, okay? And my grad student, well, you know, hair come natural fiber hairs.

Process, you

Yeah.

come off the brush. So she had to get a new brush. She knew to get a natural fiber brush. So she went to an art store, got a natural fiber, number four natural fiber brush, and didn't think about what the hairs were. But these were hog hairs. And so she she went to do the clitoral stimulation because we we kind of we got to touch the clitoris the way the male pelvis touches the clitoris, right? And so we do the clitoral stimulation and the females are like,

screaming, they're turning around, they're trying to kill her. Yeah, like she has no idea what she's doing wrong. And this lasted for about a week before she came to my office, like in tears, saying, I don't know what I'm doing wrong. I'm so frustrated. I have no idea what's going on. And when we looked at the paintbrush, it said hog hair. And I I touched it and it was prickly. Okay, because the fibers were thicker. You know, I mean think of the Von Frey hairs that you might use to test clitoral sensitivity or something like that.

Hm.

Yeah. Yeah.

vulvae sensitivity. So so they were thicker. And you know the thicker hair on the Bon Frey hair hurts. Yeah. So these females get and it doesn't go away. You can get them to have control over we can almost do CBT in female rats in the sense that we can give them an experience with a soft paintbrush, associate that with an odor, put the odor on a male, and now

Okay.

Because she has control over picking which male she's gonna have sex with, she goes with the scented male because he has the odor that's now been associated with our therapeutic intervention with this now soft camel hair paintbrush. All it takes, though, so so she'll do this and she'll have sex and everything's cool. All it takes is one prick, one painful experience again, subsequently, and now she's back in rejection mode. Right? So

Interest yeah. You never remember. Yeah. Your body remembers as they say, the keeps score or

You never unlearn it. You simply you simply superimpose inhibition over it.

Always, always, right? And when that inhibition gets removed, it just takes one painful penetration. Right? Or, you know, if they have clitoridinia, one painful thrust to the clitoris and you're back in defensive mode. Yeah.

Yeah. Back to the square one. Yeah. That's why it's kind of a lifelong battle for so many of them that they have to really like you know, even with people with primary vaginismus, I think they can easily fall into this category over and over again, but they have to kind of like, you know, there's a lot of prep work that has to happen as they always tell me. So yeah.

Of course, of course.

Well and a lot of control. You know, the put things in her control and you're and you're gonna get you're gonna get better. Yeah.

Yeah, yeah, it's true. okay, I wanna also just talk about another area of your work that fascinates me, and that's around psychedelics. And so, how did you become interested in studying psychedelics and w what do you think is happening to our processing, sexual processing with psychedelics? I know it's complicated.

Mm.

Well, psychedelics are weird because they're of course ag serotinergic agonists. So they're gonna act like SSRIs in a way. So I mean I mean I think having sex under the influence of direct influence of psychedelics is I mean, I I I don't think it's conducive. You you can try, but you're gonna be like looking at call my god, that's so red. And you're not gonna be focusing on, you know, on your partner. You're gonna be having a hallucination.

Yeah.

Yeah. Right.

But the cool thing is the because I mean even MDMA, ecstasy, methylene doxine, methamphetamine, has hallucinogenic properties, right? Especially at higher doses. So what's going to happen is your brain, you don't rewire your brain. You simply have an experience that now makes you feel a greater connection, not only with your own body, but with things that are outside in the external world.

like one experience having done LSD, I can tell you that I r I remember of course not, but I remember thinking one time that houses looked like they had faces. That is, the door was a nose, the picture windows were eyes, and the stoop was a mouth. And even though I'm not hallucinating, I can look at a house and immediately transfer

And I'm not recommending this for my podcast, so to say. Yeah.

that memory into that and say, look at that face. Because I can see the face on the house. I can see the the face on an airplane. I can see the face on a car. Right. Now that I'm not hallucinating when I do that. It's just it's a memory of what I experienced when I saw that. So I feel a connection that's very different. Cause I feel like houses are much more organic that way, right? Because they have they resemble us in some way. Okay.

I mean I feel the same way about and the entry into churches, which look very much like a labia to me, right? With the the little gargoyle on top looks like a clitoris. So, you know, it's like an and you're walking into a long tube that gets you into an inner sanctum. So it's very feminine to me in in terms of that. But so the connection that you make afterwards, and this is why it's so important, is something that diminishes depressive symptomology.

Okay.

Microdosing is not turning out to be the thing that does it. Having the full experience and then learning from that experience seems to be what does do it. And there are papers now, right, where people have had like a full experience on psilocybin, okay, over the course of a three of three months, all completely controlled. Doctors are there, so people don't jump off roofs thinking they can fly. It's like

it's the completely controlled circumstance. And in the three to six months after, so they're not doing psilocybin anymore. They they're not only does their is their depression whoppingly reduced, okay, if they have it at all, but the connection they feel to partners now is increased such that they feel like they have more arousal, more desire, and their ability to have orgasms is much better.

Right. Because all the things that were driving them to be spectatoring and you know, looking at their bodies and thinking they're not good enough and this and this and this, it's like it's all gone. It's like, now I feel like I could have a connection with you. You know, it's like, it's like, your face and my face. Where where does one end and the other begin? It's like you just have this holdover from the experience and this melting into each other, which is something you can experience at orgasm, then becomes a real thing.

Vale.

Yeah. Huh.

Right.

Yeah.

And it's like, wow, I've never felt that before. I feel so close to you. Right? And of course, you're activating oxytocin, you're activating all these things at the same time. So yeah. So I think I think what we're gonna find is that mescaline, psilocybin, LSD, you know, some of the other, you know, cathanones that produce this kind of an effect, all these things are their value is gonna be in experiencing the full psychedelic experience.

Right. Huh, that's interesting.

And the and what then the residual from that is gonna reduce depression, but without SSRS. So imagine your depressive your depressive symptoms go, you want to have sex, you can have sex, and you've got this experience that's like, wow, when I touch, I feel I feel things differently. I I I feel the Yeah, it's exactly, it's exactly like that. It's but you're but you're immersed in it.

Yeah. I it's like sensate focus, right? Like you're focused on your senses. Yeah. Yeah. Yeah.

You know, so imagine sensei focus with a blindfold on, which doesn't only involve touching the other person's body or touching your own body, but also involves just touching substances, touching a peach, an apple, or a r you know, raisins, putting your hand in raisins and what are they? And you don't know, but it's okay. Describe the feeling, you know, and that's what I think that's the value of psychedelics is that you're you're put into that, you're thrust into that.

Yeah, yeah, yeah, yeah.

Yeah.

Yeah.

And then you then you remember the experience and then you're able to

And you remember the experience and it and it feeds forward. So you're, you know, you the the connection that you have with all these things. You know, I was in I, you know, I I hugged a tree. Well, okay, how did it feel? Well, I felt I felt like like I was part of that tree. I mean, it's it's hard for people to be to maintain depression on the or even anxiety under those circumstances, because you can just go and hug a tree and calm down. You know? Yeah. Yeah, it is interesting.

Yeah.

Yeah. How to feel, yeah.

Yeah.

Yeah, yeah. Interesting, huh?

I think I think the science is very evolving and I and I do, I think it's almost like 'cause I think with sensei focus it takes time to get through, you know, to really eliminate the barriers that per you know, allow you to connect with that partner. But this kind of pushes you into it.

Sure. Absolutely. And if you I think you I think if people do it together, you know, even with a guide, I mean I highly recommend if people are gonna do this, that they have a guide who's not only done it before, but who isn't doing it at the time, so that you can, you know, if you begin to you know, you go into the bathroom and you can't see your pupils and you think you have no soul because you can't see your eyes, you need the guide to kind of calm.

Yeah.

Top.

Calm you down from that and put you into some because stuff like that happens and people freak out, right? And then they have a bad trip, as it's called. Whereas if you have a guide and the guide is guiding you both, not in a sexual way, but just in a, you know, here's the experience of have you know, you're gonna have this experience the next three or four hours, and we're gonna go into a park, or we're gonna go into the woods, or we're gonna go to a mountaintop, and what do you see, and what do you smell, and what is it, you know.

Yeah, yeah, yeah.

Yeah.

And the guide guides both of you. Now both of you had this experience. So, what happens sexually when the partners have the same experience at the same time? And I I mean, this is what happens at Raves when people take MDMA and they feel like you know they're touching each other's aura. It's it's sexual, but it's also romantic and it's also bonding, and it's also everything, and people get together.

Yeah, interesting.

Who never would have gotten together if they hadn't done MDMA at the same rave and danced with each other and touched each other's auras. Okay? I I mean it's astonishing how that works. You know, and I I know well, I know people who've gotten together who got together with that 15 years ago, and they're still together. Right? Because they had to they had a I mean it's interesting because they had a drug-induced activation of the same systems.

Yeah. Yeah. Yeah. Sounds great.

interesting. 'Cause I connect.

that normally get activated when people date and you know, the turns t it's yeah. Yeah. Yeah. And they're st and they're still together, which is I I find that utterly astonishing.

Yeah. Ex accelerated, yeah. Tutally, yeah. Yeah. In some ways, right.

Something with the connection may have happened. I don't know. Who knows? It's so interesting. Yeah. Well, there you go. I mean I'm kinda too straight laced to do that, but you know, it's nice to hear

I think so. I think so.

Well again, this is the thing. I mean, you know

I mean meaning that I'm too scared, honestly.

Here's the inverted U shaped curve and where you are, you know. Do you need it? If you don't need it, then you don't need to do it. If you if you want to do it, okay, do it and find out what it's like. And if you, you know, and if you might need to do it because your arousal levels are suppressed, then finding some degree of disinhibition and then learning how to incorporate that yourself. Because it's all your it's all about your own brain. Your own brain can do all this stuff.

Right.

Yeah.

Your own brain. Yeah. Yeah. Yeah. Yeah.

Your own brain can do this. Your own brain can do mindfulness. You don't need a drug like phlebancerin to put you into a mindful state of disinhibition. Your own brain can do that. But do you as a professional person have time to do, you know, a whole host of mindful, and then not just a whole host of mindfulness therapy, and I'm not dissing mindfulness, I think it's amazing, but to do it all the time.

Yeah. Yeah.

Yeah.

Yeah.

Yeah? I mean, can you do it all the time to be in the moment when things get sexual? Or would being on phlebancerin produce ultimately the same neurochemical effect in your brain that the mindfulness therapy is doing? Maybe even to the point that you can get off the phlebancerin and have achieved your brain's own way of doing it. Yeah? Because drugs don't drugs only affect tr you know.

Right, right.

Yeah.

Yeah.

That's really cool. Yeah, yeah, that's really cool to think about actually.

They affect receptors that are in your brain for your own endogenous neurotransmitters. If if you don't have a receptor, here's a drug, it's not gonna work if there's if the drug isn't mimicking what your own neurotransmitters are doing. There's no way. It just won't have any effect. Yeah.

Right.

Yeah. It's fascinating. Yeah, people always ask me why different and I'm like, You're only as good as a receptor that that's t at that organ, right? Like it's like, you know, that's why people respond so differently when they go on, you know, hormone replacement or, you know, testosterone or whatever. You know, I think it's it's very much like, you know, I don't know what your receptor in your hair is gonna do when you go you know, when you go on those vents or whatever, you know. So

That's very true.

Sure.

Yeah. So yeah, I'm it and again, it's important to then be able to know what the individual's baseline is. And and this is something in research that we never know unless we're unless we really get in there and say, okay, what is your baseline sexual response? Like, what do you like? What do you not like? What do you do? How do you do it? How does it work for you? yeah, we just go in with an intervention and say, okay, you're in the control group, you're in the experimental group.

Yeah.

Yeah.

Yeah.

Yeah, yeah, yeah.

Yeah.

Where does all the variance come from? Well, because these different inverted U-shaped curves are all part of your I mean, you know, you saw this with with both phlebancerin and Bremelanotide. You had responders and non-responders, right? And I'm completely convinced that the Bremelanotide non-responders would would very likely be, yeah, the Vilesian non-responders would likely be the phlebancer and ADI responders. Right? Because in one case you're amping

Yeah. And non responders, right.

Violation.

Huh. Interesting.

Excitation with Bremylanotide. In the other case, you're diminishing inhibition with phlebancerin. Okay. So if somebody comes who's too inhibited, I can't be in the moment. I'm thinking about who's going to take the kids to soccer tomorrow and who's going to cook dinner on the weekend and everything, everything. It's like, wow, we're having sex and you're not in the moment. Like, what's happening, right? That's not somebody, you know, that person has perfectly good arousal.

Right.

Yeah, yeah, yeah. Yeah.

Yeah.

But everything is all inhibited because it's like, what do I do? What do I do? What do I do? It's like, it's like ADD sex. You have no idea what to concentrate on. Yeah. So flip phlebanthrin works well for that. But there's no problem with excitation. Whereas other people have a problem with excitation. Right? So they need that that kick with the dopamine that the melanocortins produce. So they're not, they want to be in the moment.

Yeah, yeah.

Yeah, they need that dopamine hit. Yep. Right.

And they have no problem like hoping to be in the moment. Like, wow, we're cuddling, we're in the moment. Where's my desire? Where did it go? Well now ramp that up. Now you're now you're fine. So I think the responders and the non responders are people who could maybe be helped by the other by the other drug.

Yeah. Yeah.

You know, I've had some patients who try the bromolitide my Lesi and they get this like peagatty feeling for like twelve hours because they're like maybe super responding. Right? 'Cause they they feel like okay, I think

Mm-hmm. Yeah, yeah. Sure. Well well well and again, it's it it's like we have one dose, but maybe half the dose, or maybe half the dose, right? Would have been better. You know? Well, I mean it's like it's we we see this with THC as well. Right? It's like there's a very with with people that do cannabinoids, some people do it and they swear the orgasms that they have and the fact that they're

Yeah.

Would have been better. Mm. Yeah, it's so interesting. Yeah.

In the moment, they have desire, but it's a really narrow dose window with THC, right? So you go from nothing to something, but the something can go to nothing really quick if you increase the dose and start to activate the motor effects. Because the motor effects of THC are gonna suppress all that. It'll be like you're too d you're too drunk, you know, or you're gonna fall, you're gonna fall asleep, kind of thing. So it's a very narrow dose window, but for different people who are tolerant to different doses.

Dr. Sameena Rahman (01:07:39.848)

Right. Yep. Yeah, yeah, yeah.

Some people's dose windows are going to like this, and some dose windows are going be like this. And you just need to know, right? So, you know, you try two gummies, and if that doesn't work, try one. And if that puts you out, try a half. And if that puts you out, try a quarter, right? You know, because you have a known dose in there. But people are like, well, I took two and I get really horny on two. And somebody else takes two and they fall asleep. You know, because

Yeah.

Yeah.

Yeah, yeah, yeah, that's

Huh. So interesting.

Again, these these differences in sensitivity.

It's so true. Well, this has been great, Jim, and I really enjoyed this conversation. I love getting into the neuroscience. I hope people like were able to follow along and try to like, you know, really understand some of this stuff. I mean, obviously we'd love to have more research on women and women's sexual response and stuff. and I always say like women are not rats, but like we can learn stick things from like basic science perspective from these things as well. 100%.

Yeah, great. Yeah, me too.

Of course, of course,

absolutely. Absolutely. Yeah. So yeah. Well I'm really glad you had me on. That's cool.

Yeah, it's cool. so it so thanks Jim to everyone listening, your sexual response isn't one hormone or one neurotransmitter or one body part, it's really a full system. So I thank you for giving us a better understanding and you know when your book comes out I'll have you back on and we can actually like get into the nitty-gritty of it.

Sure.

Perfect. Perfect. Thank you, Samina. Take care.

All right, thanks. Thanks everyone for joining me today for Guido Girl Presents Sex, Drugs, and Hormones. I'm Dr. Smeena Rahman. Remember, I'm here to educate so you can advocate for yourself. Please join me next week.