The Liz Moody Podcast - Is Nicotine Actually...Good for You? New Research on Memory, Focus, and Mental Health

Episode Date: September 24, 2025

For decades, nicotine has been synonymous with smoking and disease but recently people are claiming nicotine patches have been improving their health—so what’s the truth? In this fascinating conversation, Vanderbilt neuroscientist and psychiatrist Dr. Paul Newhouse dives into the science to reveal the surprising ways nicotine impacts the brain, from Alzheimer’s and ADHD to depression and long COVID. In this episode, we unpack: Why nicotine is not the same as tobacco What the groundbreaking MIND Trial shows about nicotine and Alzheimer’s Whether nicotine can improve focus, memory, or ADHD symptoms How nicotine may regulate mood, depression, and anxiety Surprising effects on weight, hormones, and blood pressure The truth about nicotine addiction, delivery methods, and dosage ✨ This episode completely changed how I think about nicotine and its potential role in modern medicine. It’s a powerful reminder to question assumptions and dig into the science behind our health beliefs. ✨ Homework: Write down one “health fact” you’ve always accepted as true—then do a little research to see if the science actually supports it. For more from Dr. Paul Newhouse, visit his Vanderbilt University profile. Ready to uplevel every part of your life? Order Liz’s book 100 Ways to Change Your Life: The Science of Leveling Up Health, Happiness, Relationships & Success now!  Connect with Liz on Instagram @lizmoody or online at www.lizmoody.com. Subscribe to the substack by visiting https://lizmoody.substack.com/welcome. Buy our cute sweatshirts, conversation cards, and more at https://shop.lizmoody.com/. Use our discount codes from our  highly vetted and tested brand partners by visiting https://www.lizmoody.com/codes.  To join The Liz Moody Podcast Club Facebook group, go to www.facebook.com/groups/thelizmoodypodcast. This episode is brought to you completely free thanks to the following podcast sponsor: Seed (DS-01): head to Seed.com/LizMoody and use code LIZMOODY for 25% off your first month.  The Liz Moody Podcast cover art by Zack. The Liz Moody Podcast music by Alex Ruimy. Formerly the Healthier Together Podcast.  This podcast and website represents the opinions of Liz Moody and her guests to the show. The content here should not be taken as medical advice. The content here is for information purposes only, and because each person is so unique, please consult your healthcare professional for any medical questions. The Liz Moody Podcast Episode 367. Learn more about your ad choices. Visit megaphone.fm/adchoices

There are so many things that people online are saying this is like a miracle solution for. So tell me what the research shows at present. I have always thought that nicotine was terrible for us. On its own, is it bad for us at all? Or is it just when combined with tobacco? Well, this is a problem and a question that has bedeviled us for 150 years. Nicotine comes from the tobacco plant primarily, but it can be found in many different plants, including tomatoes. It has clear effects on the brain, and that's presumably why people find smoking to be reinforcing and habit-forming.

But nicotine by itself is a complicated chemical that has a whole range of effects. Many of us have been interested in can we use nicotine medicinally? Can we separate the effects of nicotine from the effects of smoking? And can we learn something about how the brain functions? I think there's evidence that nicotine can produce improvements in attention and memory for some patients with memory loss. I'm Paul Newhouse. I'm a physician and neuroscientist. I studied the brain for the last 40 plus years. I'm a professor of psychiatry and neuroscience and pharmacology at Vanderbilt University and Vanderbilt University Medical Center. And my focus is on chemical systems in the brain important for learning and memory and in the risks.

of Alzheimer's disease, particularly for older women. That's so interesting that it's in tomatoes and things like that, because our brain has nicotine receptors, right? And I've always been like, why does it have nicotine receptors? Like, for what purpose? So nicotine is an analog at a certain brain receptor or brain a signaling mechanism that involves a naturally occurring chemical in the brain called acetylcholine.

And acetylcholine is the normal signaling. molecule or neurotransmitter that communicates between nerve cells, including your muscles, including your spinal cord, and particularly the brain. Nicotine imitates the shape of acetylcholine at that receptor in much the same way that derivatives of the poppy imitate the shape of the opiate receptor. And so there are a lot of plant chemicals. And the reason we call it the nicotinic receptor was because over 150 years ago now, the two receptors for acetylcholine were separated into two basic types, muscarinic, nicotinic. So in the simplest terms, what does that receptor do in your brain? The area that my work has been focused on is trying to understand what that nicotinic

receptor does, that nicotinic acetylcholine receptor. We think it's very involved in modulating the brain activity in various brain networks and circuits. So what do I mean by modulating? I mean that it can amplify or dampen the effects of other neural circuits in your brain. It can ramp them up when it needs to. It can quiet them down when it needs to. It really depends on the particular environment that you're in. It depends on your particular state of mind, and it depends on your biology. But nicotine acts like an amplifier of different brain systems, both inhibitory and excitatory. Wait, that's so interesting. So is that why sometimes it will make you calmer, but sometimes it will make you more energized because it's amplifying the state that you're already in? Or is it

responding to the state that would balance how you feel? The brain and the body wants to be at a good point, right? And so if you're very anxious, nicotine may actually bring you calmer, but if you need to be more hyper-alert, nicotine may actually do that as well. So the brain has a lot of systems that are trying to produce a balance process. and nicotine can act on those systems to do that. And in fact, that's why I've called it in the past the perfect psychotropic drug. It makes you calm when you're agitated and it can make you a little bit more agitated if you're too calm.

And so I think that's why, in part, certain people are drawn to using tobacco or other nicotine products. Are all of the effects that one is feeling when they like smoke a cigarette or they vape the psychological or the physiological effects? Are all of those effects due to the nicotine or is there other stuff in there that's making us feel what we feel? The answer is not entirely clear, but I suspect that the majority of the effect is related to nicotine. In other words, it's been shown many, many years ago that smokers won't smoke if you have

the denikotinized cigarette, right? There's no reinforcing, habit forming, or pleasurable aspects to smoking without a little bit of nicotine in there. So nicotine seems to be necessary for smoking, but it's not sufficient on its own. And then going back to my original question, is there research that shows negative health effects of nicotine in absence of tobacco at this moment. That's a very controversial and very important topic, right? Because there are companies now marketing non-tobacco nicotine products, nicotine sprays, nicotine vapes, nicotine pouches. So the question of whether nicotine by itself is damaging to your health is currently under investigation. and we don't have all the answers to that yet.

Now, we've shown in our work that in therapeutic studies, we can give nicotine long-term to non-smokers, even elderly non-smokers, without negative health effects that we can detect. And in fact, you probably know about the mind trial that's soon to read out, and we will have the longest database of non-smokers using nicotine that's ever been published, We hope to have that result out early next year. And that will look at the health effects of long-term nicotine use in non-smokers. And we hope to know some answers at that point.

Right now, we think it's reasonably safe. So tell us about the mine trial. How long have you been studying people using nicotine for? So the mine trial was started before the pandemic. It certainly got put on the back foot because of the pandemic. but we started actually in 2018. And we've been studying the long-term effects of nicotine on memory and attention in patients that have memory loss.

Each patient in the study gets up to two years of treatment. A long time taking nicotine on a daily basis without cigarette smoke, without using tobacco. The FDA was okay with us going ahead with that trial because we were able to present. some long-term safety data from other studies that suggested that our, and our own previous studies that suggested it was safe. When you're doing trials, how are people consuming the nicotine? So in our studies, it's all transdermal. So it's with a nicotine patch worn on the chest or worn on the arm. That's a very slow way of absorbing nicotine. And in fact, it's so safe, it's sold over the counter. You could walk down to your local Walmart and buy

nicotine patches over the counter and no one would question you. You don't have to show ID. You don't have to, you know, it's so safe that there's just no abuse potential from nicotine patches because it doesn't produce any much of the sort of reinforcing or pleasurable effects of smoking or vaping. Is it addictive still, though, to have the patch? It doesn't appear to be in our hands. And so we've been able to take people off abruptly with no side effects, no withdrawal, no craving, nothing. Okay. Tell me about that because in my head, nicotine was the addictive part of vaping or smoking. Like that was the part that people were addicted to. You know, there's a lot of things we believe that just ain't so, you know. And it turns out that nicotine by itself doesn't appear to be

very addictive. It all, it depends, however. It depends on. It depends on. the speed of administration and the route of administration in terms of how habit forming it is. And so smoking is a very rapid way of depositing nicotine into your bloodstream, right? Within seconds, the nicotine is actually flowing to your brain. And so it turns out that the rate at which you administer this drug seems to have a lot of influence on whether people desire to continue using it. There also seems to be something about habit forming about the act of inhaling and chewing or chewing. That oral mechanisms seem to be very reinforcing, very habit forming. Whereas slapping a patch on your chest, you know, you don't see kids trading nicotine patches on the playground, do you?

You know, nobody wants to go out and use this stuff unless it's in a form that people can get rapid, essentially. eventually traffic up to the brain, rapid bloodstream effects. And so that seems to be important with nicotine, which doesn't seem to be the case with other drugs of abuse. Oh, that's so interesting. And are the patches you're using in your trial, like literally the ones that we could walk down to the store and get? Are they? Literally the ones. Oh, wow. The same ones. Okay. I'm going to share a number of conditions that I have heard that nicotine helps with. Okay. There are so many things that people online are saying, this is like a miracle solution for. So I would love you to tell me what the research shows at present. And also if you have any speculation, because again, you're the world's leading expert in this subject.

So if you think we're going to find something out in the future, I'd love just, you know, your opinion as well as an expert in this field. Let's start with the one that probably has gotten the most conversation, Alzheimer's. What does the research show at present about nicotine helping with Alzheimer's prevention or treatment? Well, that's the subject of my research really since the 1980s, actually. I started by giving intravenous nicotine to Alzheimer's disease patients in 1985. We didn't have patches. There was no gums. There was no nothing. We had to make nicotine on our own and actually give it by intravenous infusion. I think there's evidence that nicotine can produce improvements in attention and memory for some patients with memory loss. Now, is it specific to

Alzheimer's disease, I'm not entirely sure yet. There's evidence that nicotine improves attention and executive function and maybe memory, actually in a lot of different conditions. And so, is it specific to Alzheimer's disease? I'm not sure. But I think that there's reasonable evidence that nicotine could be helpful to patients who are experiencing memory loss from Alzheimer's disease and perhaps other causes as well. Is that just for treatment or if somebody, say, gets tested and they have the gene that increases their likelihood of getting Alzheimer's, would they maybe want to try a nicotine patch in order to help save that off?

It's a fascinating question, Liz. And one that we've begun to think about. In other words, could it be used as a preventative treatment? The word we use in medicine is prophylactic, right? Can we use it as a prophylactic treatment? That's never been tested. and the answer is we simply don't know. Epidemiologically, in other words, using real-world data,

people have looked at smoking as a way to prevent Alzheimer's disease. That clearly does not work. So smokers actually have higher risk of dementia, and that's probably because of all the negative effects of smoking. There hasn't been enough population use of non-examination use of non-tobacco nicotine yet for us to answer that question. I don't think there's going to be any big prevention trials with nicotine in Alzheimer's disease at this point.

I think that would be a tough cell to the NIH at this point, especially with the current administration. Based on your understanding of what's happening with nicotine on a mechanism of action level, though, and your understanding of what Alzheimer's is doing in your brain, would you speculate that it would be helpful? We know that the colonergic system, that's the system that nicotine is acting through, is one of the first systems to deteriorate an Alzheimer's disease. And so one might ask oneself, well, if that's the case, then would stimulating that system

with nicotine be helpful? And that was part of the reason we're doing the mind trial, right? And then could we actually prevent that? I think it's an interesting question and check with me in a few years and maybe I'll have the answer. I think it's a reasonable hypothesis that it could be helpful based on a mechanistic standpoint. Could we actually prevent or enhance the colonergic system to the point where it resists the effect? I don't think, what I don't think will happen is I don't think that nicotine would block the molecular damage that is causing Alzheimer's disease. That, part I don't think will have. Okay. What would that mean in layman's terms if it's not blocking the

molecular damage? What it means is it would enhance the system's ability to resist the effects of the molecular damage, right? So in other words, you're essentially pushing the symptoms back a little bit. I don't think it's going to interfere with the actual mechanism of the disease. Now, there are trials that we're doing now, which are aimed at actually doing exactly that, preventing the molecular events that lead to Alzheimer's disease. But that doesn't involve nicotine. As one of the world's leading researchers in Alzheimer's, how close do you think we are to being able to truly prevent it or truly cure it? I think we're closer than we've ever been in my career in 40 years, right? So I think we have the first real tools.

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Liz. I have two kind of nitty gritty questions and maybe a little bit silly questions and then we'll get back to my list of conditions that I want to know what the research shows about nicotine impacting. But for tobacco is tobacco in itself

bad for you or is it just when you burn it? Like if you just had tobacco in your mouth or you were drinking as a tea or stuff like that, is that bad for you? Probably, yes. Okay. Yes, it turns out tobacco itself is a product that we should not consume, right? I mean, there's no, there's no accident that nicotine was used as an insecticide a hundred years ago, right?

Nicotine was? So because, oh yeah, in fact, the original black flag was powdered nicotine. Wait, so I thought that nicotine was safe and tobacco is bad. So why was nicotine used as an insecticide? Because if you administer enough of it, it'll be, toxic, like a lot of other things, right? So, you know, those old English murder mysteries, there was the poison was nicotine in the garden shed, right? The liquid nicotine that was used on your roses. So tobacco, you're like, this has thousands of compounds. Many of them seem to be carcinogenic, no matter how much your dose is. Nicotine, you're saying this has a bunch of different compounds from what we understand. If the dose is correct, those compounds are not carcinogenic.

insofar as we know. Great. So nicotine by itself is not carcinogenic. And in fact, people have looked hard to see if it even promotes cancer and does not. So there's really no evidence that nicotine by itself is carcinogenic. But like many drugs, nicotine is poisonous if you take enough of it, right? So nicotine can overwhelm your system and it can produce all sorts of unpleasant side effects, which, you know, anybody who smoked a cigarette can attest to, right? So, you know, you might feel nauseous. You might vomit if you take too much of it or you might feel dizzy. And if you take even more of it, it can produce even more unpleasant side effects. So, you know, as we all know, there's a famous saying in Latin from the 14th century, the dose makes the poison.

My mom always told me that I wouldn't ever want to smoke a second cigarette, that I would never get hooked on smoking because the experience of smoking a first cigarette was so unpleasant. But I proved her wrong in college by becoming a pack a day smoker. Oh. I don't smoke anymore. I haven't smoked in decades. But question number two, that's potentially a little silly. But I am curious, is there any research on strangely positive effects in smokers just because there are millions of smokers all over the world?

And we know, again, that tobacco is carcinogenic. but if there are weird, positive things that are happening, would we be able to sort of backtrack and attribute those to nicotine? So there's been a story kicking around for 25 years at least that smokers have a lower incidence of Parkinson's disease than we would think that they would, right? That in some way, people who smoked have less Parkinson's disease. And people have been trying to figure this out for decades, right? Is it a nicotine effect? Is it something we don't understand about cigarette smoke? Why would cigarette smoking protect against Parkinson's?

So people have looked hard for evidence that cigarette smoking might have some beneficial effects. So, for example, for a few years, people were interested in why smokers seem to have lower incidence of ulcerative colitis. And as we know, in other patients with mental illness, smoking is very common. And why is that? Is there some beneficial effect of cigarette smoking or nicotine exposure for people with ADHD or other mental illnesses? And the answer is almost assuredly the answer is yes. And so there are beneficial effects for nicotine or cigarette smoking or perhaps nicotine pouches or something like that, right? And so I think the short answer is there are some beneficial effects for some people.

Yeah, but to be clear, don't smoke. Don't smoke. We're not recommending anybody smoke. I like to say nicotine is a good drug, but tobacco is a bad delivery system. That's great. Okay. Going back, you mentioned Parkinson's. What does the research show at present about nicotine's impact on Parkinson's?

Well, nicotine by itself does it. seem to help Parkinson's disease patients very well. So I haven't, I conducted some very early, like, acute trials back when I was in my salad days, you know, when I didn't have all this gray hair on Parkinson's patients. And we saw some potentially beneficial effects, particularly on thinking, because Parkinson's disease does affect your thinking. But studies that have been done trying to identify beneficial effects on motor function, haven't really found that much that's been beneficial. A colleague of mine who's now retired was a primate researcher, and what she showed was that nicotine seemed to reduce the excess movements that one gets with aldopat therapy, the what we call

discinetic movements, the abrupt, uncontrollable movements that one sometimes sees with aldopatotherapy. be my mom had Parkinson's disease and she got all these extra movements from her treatment, right, that were hard for her to control. And nicotine seems to improve that. We don't fully understand why the possible explanation gets very technical and I would bore you to tears by explaining it, so I won't. But just giving nicotine to Parkinson patients who are already ill, again, doesn't seem to have a whole lot of benefit. What is the research show right now about nicotine and ADHD? We did show ourselves in some experiments that we published about 15 years, 20 years ago now,

that nicotine improves some of the cognitive deficits that are particularly found with ADHD, mainly the kind of what we would call impulsive responding. So people can modulate or inhibit themselves a little bit better when they have nicotine on board. Now, by the way, amphetamine does the same thing. So actually, stimulant drugs do it as well as nicotine. So that's why stimulant drugs are helpful to people with ADHD. There has been a number of companies tried to develop nicotine selective agonists over the last 25 years. So I was involved with a number of companies that were developing sort of super specific versions of nicotine that would hit this subtype of receptor or that subtype of receptor because there was thinking that, well, nicotine is a kind of dirty drug.

It hits all the nicotine receptors, right? What if I just pick out this population of receptors? Maybe I'll get a very specific effect. And that was tried in ADHD, and we showed that it produced some benefit, but for a variety of reasons, the companies all ended those development programs, mainly because the benefit wasn't large enough, they felt for them to really market these as drugs. And so all of those development programs in which there were probably half a dozen companies that were pursuing subtype specific nicotinic agonists, all of those have closed now. And we're back to nicotine. A lot of biohackers are using nicotine to increase their focus in energy. Have you found that the research supports that? The way I've explained this to people when I speak in public or to podcasters is that it's very hard for nicotine to improve your focus or

attention if you're functioning at peak performance. You won't improve. In fact, you'll get worse. It's what we call baseline dependency or rate dependency. It all depends on where you are at the present time in whether nicotine is going to have an effect. So what do you think these biohackers, or I heard a famous neuroscientist say that he uses it? Do you think they're just at the lower end of the U-curve? And that's why they're experiencing these benefits?

I think that nicotine is unlikely to improve good performance in people. we've not been able to show that. Other people haven't been able to show that. It's not going to make your performance super normal. Now, you could argue, well, Paul, could nicotine help sustain my optimal performance? That I don't know. In fact, it's actually one of the fascinating questions with nicotine, because, and this is going back to the biology again, nicotine desensitizes those receptors we talked about, very quickly, right? So, in fact, because they're so sensitive, those receptors turn off very rapidly once you flood them with nicotine. And so the question you always get is, well, but what's the long-term effect of nicotine? You know, what if you just keep giving people

nicotine? What happens to them? Now, in our hands, in our studies, we showed long-term benefit. but that's in an impaired population. So in an impaired population, yes, we could see sustained benefit. In a normal population, I'm not sure you could. I just think the word normal is so tricky these days. Like, you're like, oh, it could increase energy if you're low energy. It could make you calm if you're anxious. And I'm like, everybody I know is low energy and anxious.

And I don't know if that's on a physiological level or if that's just because that's like the state of the world these days. Well, we do live in interesting times, no question about it. And we are all all searching for ways to modulate our anxiety or modulate our state of mind. But humans have been doing this for millennia, right? We've always been wanting to alter our state of mind. Nicotine can clearly do that, for sure. Do some people benefit from chronic nicotine?

I am sure that some people do. I don't know if it's biohackers or, you know, tech executives or neuroscientists. I did have a colleague who was a very prominent nicotine researcher who told me we met when he was a graduate student and I was a postdoc and he told me that he used nicotine in those days. It was just like dripping it on your tongue. But he was studying nicotine in the lab and he started to try using it himself late at night to get his dissertation written. I guess my question is, if you try it, if you put a patch on and you feel like you improve, does that mean you are probably on the lower end of the U curve? And that's why you're experiencing that benefit.

It depends if I tested you, like if I put a patch on you and I tested you pre and post and I control that with a placebo patch just to make sure we weren't both fooling ourselves. We would have to see. I mean, I think that some aspects of your performance could improve. Would you be able to detect that in your own life? I'm not sure. But if you were having trouble with focus because you have ADHD or because you have other emotional difficulties,

if you suffer from depression or anxiety, could nicotine help that? Yes. In fact, we're studying. we're studying the effects of nicotine on depression. What have you found so far? So this is work that I'm doing with my colleague Warren Taylor, who leads this research, but we have been using nicotine as an augmentation treatment in late life depression,

in patients, older patients with poorly treated depression. And we found a dramatic effect in terms of rapid improvement of moot. We're very excited about this. And he's a big depression researcher. that's really not my area. But he came to me when I prodded him to do this study years ago. And he came to him and he said, my gosh, this is the biggest antidepressant effect I've ever seen. And why is that?

We think that nicotine actually may enhance certain cognitive functions that are impaired by depression. And could this be extended to even people not in late life? I think it could be really interesting to find out. Are there different mechanisms for depression later in life than there are earlier in life? Is there any reason to think that it wouldn't extend? Well, we know that in late life, patients with depression, this is his work, not mine, suffer what we call executive dysfunction, right? So their ability to plan and to manage their attention and manage their cognitive function declines.

and nicotine seems to specifically enhance that function. Which is also why it would help with ADHD, right? Which is why it would help with ADHD, exactly. Yeah, you hit the mark with that comment. So we think that executive function may be specifically enhanced by nicotine, even in late life, whether this is as much of a problem in earlier middle life, unclear, but we think that there's executive impairment, even in younger people with depression as well. So could it be an augmentation treatment? Yes. How does nicotine compare with ADHD

treatments that currently exist, like Adderall or Ritalin? The dose is the devil in this, right? So what's the right dose? Is the effect as sustained as the effects of amphetamines or stimulants we don't know because it's never been given long term. I can tell you that some of the long-term nicotine agonist trials, the ones with these selective molecules, showed fairly modest effects compared to stimulants. And so it may not be the best treatment in terms of stimulant effects, which have just a whopping effect on ADHD symptoms.

but I think it's possible it could help certain cognitive difficulties that these folks have, that maybe the stimulants don't help. And then speaking of dose, do you need more nicotine over time to have it still work if you're using it for some sort of condition? That's what I initially thought. And in fact, years ago, we did our initial big pilot trial with 75, 72 patients that we did with mild memory loss. We did it at the highest nicotine dose,

like 20, you know, the highest dose we could patch we could get. And I had a colleague come to me who's a molecular guy, and he said, Paul, I think you're using way too much nicotine. Because in our studies in the lab, we can see all these effects at much lower levels. And I said, you know, you're probably right, but I don't have the human data to back that. My colleague, Warren Taylor,

has come back to me with his depression study and says, you know, I think less is more here. We may not need those high doses that smokers use to get beneficial effects. And I think he's going to turn out to be right. So I don't think you necessarily need a high dose. Our patches, this is, I'm sorry, I've not used nicotine, but are patches available in different doses? Yeah. So commercial patches in this country are 7, 14, and 21 milligram. So the idea there was to work people up to this highest dose because we really didn't know how much nicotine you need chronically.

It's one of those studies that's just never been done. But I think the data that I'm beginning to see makes me feel like we may have overshot the mark here. What dose are you seeing effects preliminarily at? Yeah, in the depression study, which we published, again, preliminary data. So to be that as it may. open label preliminary. We saw benefit at around seven and a half to 10 milligrams a day rather than 21. And in fact, we had more intolerance, of course, at the higher doses. You expect that. And people seem to get benefit at lower doses. If you take a seven and a half milligram dose for

a month or two months, is there any evidence that that would stop working and you need to go up to like a 10 and then a 14 and then a 21 because that smaller dose would stop working over time? No, there's no clear evidence on that either way, actually. So we don't, you know, people, what we call titrate themselves, right? So if you started to take nicotine, you know, recreationally or because you thought you needed it cognitively, you would kind of find the dose that your body could tolerate and you would probably stay there. And I think that's kind of where, you know, most people are, right? It turns out that there may be, you know, people who can tolerate much higher doses than you or I could.

But, and for them, they might need higher doses. I mean, we know this, right? That there are differences in doses. But the general rule is, is that with really higher doses, all you get is more side effects. You don't get more benefit. When you think about strength and resilience, like your ability to feel energized, to recover well, to stay strong as you get older, what do you think that actually comes from? Most people say working out or good nutrition, and yes, of course that matters. But there is a biological foundation underneath all of that that most people are completely

overlooking. I have been diving deep into this lately with the team at timeline and what I've learned has genuinely shifted how I think about my own health. Every single movement that your body makes, every step, every workout, every muscle contraction depends on energy produced at the cellular level. And at the center of that is your mitochondria. Here is the thing that nobody tells you, certainly nobody told me, starting around age 30, our mitochondria naturally become less efficient. More get damaged, more become sluggish, and over time that impacts your energy, your strength, your recovery, and your resilience. Most of us respond by pushing more. We're like noticing these things and we're adding in more protein. We're trying to fix it with

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Timeline has done over 15 years of research and testing on this one product, urolithin A, which, by the way, most of us lack the gut bacteria to synthesize naturally. That's why many of us need to supplement it to get the benefits. This has become a staple supplement for me. It is my top way to sport how I want to look and feel as I age. Support yourselves and how you age with mitopure gummies from Timeline. Visit Timeline.com slash Liz and save up to 39% on your mitopure gummies. That is timeline.com slash Liz. The number one rule of habits is to make the things that you want easier and the things that you don't want harder. Yet so many of us want to eat healthier, but so few of us actually take the steps to make eating healthier easier. That's where

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could be helpful to the cognitive difficulties, the mental and emotional difficulties that people have following COVID. There, of course, are large trials now that are studying long COVID with other drugs, particularly antivirals or drugs that affect the immune system. Nicotine is reported to be helpful from different cases. And as you know, on the internet, people report this. And I've been contacted frequently by people looking for answers regarding long COVID. We don't have any controlled data at this point. And so I think the answer will have to await some trials. anecdotally, people report it's helpful, but that's very inter-individual. I think some people will find it helpful. Other people may not, and we don't hear from those people. Yeah, that's true. Based on,

do we know what's happening from a mechanism of action perspective with long COVID in a way that we could speculate about why nicotine would or would not be helpful there? Or is that still more of a mystery? I think the answer is a qualified yes, because we know the mechanisms which people report that they have trouble with seem to fit with what we know about what nicotine helps with, which is executive function and attention and some of the emotional difficulties that people experience. People have reported these kinds of effects for decades, right? So I can remember even back in the day when we studied nicotine effects in Parkinson's, we had a few people come to us and say, look, it's not really helping my motor problems very much, but it really is helping me think clear. And so could

nicotine be for folks who suffer essentially COVID brain or brain fog? I think it's possible. Do the effects of nicotine ever last after people stop taking it? Like, does it ever actually rewire your brain in a way that you would see a lasting benefit? Or is it sort of symptom mitigation in the moment when you would be taking it? Well, we don't know the answer to that either, I'm afraid. some hints. So many years ago, there was a brief flurry of interest in treating children with Tourette's syndrome with nicotine. And Tourette's syndrome, as you may know, is this unusual neurologic syndrome where people have these sort of barking noises or cursing or motor movements. It's kind of related, have obsessive, kind of compulsive rituals and

things. It's a very debilitating problem for certain children. And there was a group at one of the Florida universities that got really excited about some potential adding nicotine to the other drug treatments and getting this like amazingly extended effect from like a single dose that lasted days or even weeks. We don't generally see that in other conditions. So we have not seen sustained effects. Now, I have to qualify this a little bit because when you take nicotine chronically, where anyone takes nicotine or smokers take nicotine, they actually change the number of nicotine receptors in the brain. So actually, the number goes up.

So nicotine has this weird effect of actually increasing the number of nicotine receptors in the brain. Now, that's different from other drugs, which often if you flog your brain with some other stimulating agent, you may actually decrease. The brain tries to adjust to that by saying, oh, no, no, I'm getting too much signaling. I'm going to ramp down the number of receptors. But in nicotine, it goes the opposite way, probably because of the desensitization effect that I mentioned earlier. And so a smoker has more nicotine receptors than a non-smoker. And could that have long-term benefits? Yeah, it's possible. But that doesn't mean that you need more nicotine to

stimulate all of those new receptors to get the effect? We don't think so. Now, we've argued for a long time, and we still are arguing about whether the effects of nicotine are due to long-term stimulation or long-term desensitization of these receptors. My answer is that it's actually a mix of both effects, that some receptors are desensitized, and that may have one set of beneficial effects. as well as the stimulation of the remaining sensitive receptors. And so I think there's no simple answer to this.

We actually have some colleagues that are proposing some studies to try to suss this out. But we still, even after all this time, don't know whether nicotine's effects are mediated through one or both mechanisms, actually. It's probably a mix. Do you need to build nicotine up in your system over time for it to work? or can you be like, I feel brain fog today. I'm going to slap on a patch and then my brain fog will go away. It's potentially true that you could have beneficial effects or negative effects of nicotine within a very short period of time. Now, again, it relates to what we talked about at the top of the podcast when we talked about everything's dependent on the rate at which it enters your bloodstream.

So if it enters fast, like through your lungs or something like that, then, the effects on the brain are going to be very rapid within minutes to an hour. But if it enters really slowly, like through a patch, then the effects aren't going to be instantaneous. But you would feel effects that day. You don't need to, like I just did an episode about creatine. And for creatine, you need to build up your creatine stores in your body before you start to experience positive effects of creatine. Nicotine isn't like that where you need to build up a certain amount. Not like that at all. again, it has a very rapid effect on those neurotransmitter receptors in your brain, spinal cord, your gut.

I mean, you can reflect back to your own days when you tried, started cigarette smoking. When you first had a cigarette, I'm sure the effects, the unpleasant effects, didn't take very long to appear. No, they didn't. And what I was addicted to there was the smoking of the nicotine, not the nicotine itself. Right. So there's something so reinforcing about holding a cigarette in one's hand and inhaling it. I mean, it's a habit forming procedure, if you will.

How does nicotine impact our hormones? So I did publish a little bit on this back in the day. It's been many years since we've looked at this. It will stimulate the adrenal glands and to release adrenal hormones like cortisol. It probably does this both directly affecting the adrenal glands itself, but also indirectly through stimulating the secretion of signaling molecules to the adrenals. So we did study this a little bit, and nicotine does affect those hormones, at least acutely. Now, chronically, I'm not so sure. I've never looked at the question of how nicotine affects stress hormones chronically.

I suspect that it probably has some effect, but that effect may fatigue or disappear after a while. Because, again, the body tries to establish an equilibrium. Does it affect sex hormones? Not to my knowledge, not in a big way. I don't think there's much evidence that it affects estrogen or testosterone. Or if it does, the effect is only at the margins. it does affect stress hormones acutely, but I don't know about chronicly. Yeah, it's interesting because a lot of the symptoms that we've talked about nicotine alleviating,

I would imagine are pretty common in perimenopause and menopause, and that's a huge conversation that's being had these days. Are people using nicotine for that? That's one I have not heard. I have not heard of women saying, oh, I'm using nicotine to alleviate vasomotor symptoms in perimenopause, for example. Not heard that. Yeah, that's really interesting. I just feel like that conversation is just really ramping up.

And so people are acknowledging the symptoms and trying to research different ways that we can potentially alleviate those symptoms. How does nicotine impact sleep? So nicotine is not beneficial for sleep, as far as we can tell, actually. And in fact, in the mind trial, we actually have people take the patch off before they go to bed. because if people have a lot of circulating nicotine, or at least non-smokers, if they have a lot of circulating nicotine, they report either excess dreaming

or just interrupted sleep. So we think that nicotine is not good for sleep. The colonergic system as a whole is kind of an alerting system, right? So if your colonergic system is going 100%, you're going to have trouble going to sleep. And so we actually don't think it's good for sleep. Even if we are excited and then nicotine is trying to balance us out.

Like my grandma used to always say that she needed a cigarette to fall asleep because she was overstimulated. So the idea is that, as you said, I believe it would balance us. If we're overstimulated, would it balance us for sleep? I mean, it is true that smokers, chronic smokers, maintain nicotine levels actually throughout the 24 hours, right? So, but you know that it drops in the night because people will start smoking in the morning, right? And I, but I don't think that there's good evidence that nicotine by itself is

soporific or has, you know, helps one fall asleep. In fact, our anecdotal data and our side effect data report that people actually complain about it at night. In fact, that's true with other cholinergic drugs as well, interestingly. So the ones that were developed 25 years ago for Alzheimer's disease, like Denepazil, we also tried to not have that drug given close to bedtime because it just keeps people. Have there been any studies on nicotine and heart health, either positive or negative? Well, there have been huge studies looking at smoking in heart health, and they're all negative, right? So particularly all of the carbon monoxide that's in cigarette smoke and all of the other chemicals that are just noxious for your heart. So smoking 100% bad for heart health.

Nicotine by itself, there are always worries about it, right? Like would it be overstimulating to the heart? But in practice, we've seen very little effect on chronic heart disease or heart health. And we've been giving it now, like I said, in the mind trial for up to two years and we have not seen an excess of heart problems in our treated patients thus far. I will tell you a funny, interesting piece of data. In our initial trial that we did for six months, it was six months of nicotine treatment. We actually saw blood pressure go down in our nicotine treated group. In fact, I had somebody look at this and they

said, well, geez, nicotine looks like a good anti-hypertensive here because it actually reduced blood pressure. Now, it's fascinating. We don't really fully understand why that would be the case. And in fact, I remember presenting this at an FDA meeting and this cardiologist said, she said, I don't believe this data. And I said, well, I can't help you with that. This is the data. You can, I mean, these are the numbers. I mean, you know, it is what it is. some people you know this we have thought that maybe the weight loss that nicotine produces and nicotine does produce weight loss has something to do with blood pressure effects i'm not sure but you know that's one of the most reliable effects of nicotine is to actually reduce weight and why is that

again it's not fully understood but it seems to suppress appetite um people eat less when they when they smoke. And in fact, in our studies, our initial study, people lost about five pounds on average, but it plateaus very quickly. So what we found was that in our initial study was that people lost about five pounds over the first three months of using a nicotine patch, but then they plateau. And so it's not like the GLP1 drugs where people lose sustained amounts of weight and keep going. So it's never going to compete with all those GOP-1 drugs. But there is a definite effect on appetite. Are there any other positive effects of nicotine that we haven't touched on yet?

One of the most interesting questions, again, is mood regulation and stress and anxiety regulation. I think I have some colleagues who are launching a big study of non-tobacco nicotine use. in the real world, like people who are just using it. And I have asked them to really focus on mood and anxiety. And they're actually going to be tracking people using smartphones, right? In real time, like, how do you feel right now? They're going to be sending them messages like two or three times a day. Just tell me what your mood is right now and what your stress level is right now.

and then counting the number of times they use a pouch or a vape or something like that. And because I think people are using this for their emotional regulation. And I think we need to understand that a lot better than we do now. Because even if you aren't suffering from full-blown depression or clinical depression, maybe people are successfully using this to regulate their emotional state. Interesting. How do you think we would be talking about nicotine if it were discovered right now and it didn't have the whole tobacco association? I think it would be regarded as a drug and we would be exploring it for a lot of different things. Although, in a sense, we actually are benefiting from its long history because now people, there's, you know, billions of humans have used nicotine, right? In one point, form or another. And so we know all these fascinating effects on mental illness, on emotional

regulation, on cognitive function, on everything from ulcerative colitis to Parkinson's disease. I mean, we would have none of that data if people didn't use nicotine, you know, for thousands of years. There's some concern that I've seen that nicotine companies are seeding nicotine online and in the wellness world, similar to how cigarette companies tried to get people hooked a long time ago. And that's why all of the sudden we're talking about it is this really healthy thing after not talking about it for years. Have you seen any evidence of this? A drug company is never going to develop or sell nicotine as a drug because anyone can make nicotine. It has no IP left.

And so when we approached the patch companies years ago about helping us co-sponsor treat long-term treatment studies for memory laws, they were like, nah. Because there's no, you know, even if the drug, even if it got a FDA approval for this, anyone could sell it. And so they're not going to invest money in something that has no intellectual property value. So it was never going to be developed as a treatment by a company, which is what you have to do to get FDA approval. Yeah, that's interesting. How have you gotten all of your research funded then? My funding has come from the NIH through the National Institute on Aging, specifically through their Alzheimer's Disease Research Program and their clinical trials program. They've been the ones that have funded this.

I've never gotten any funding from tobacco companies or anything like that because none of the, them are interested. If somebody wanted to experiment with nicotine for any of the conditions that we talked about today, they're like, I have executive dysfunction, I have depression, I have anxiety, what advice would you give them specifically? Like, what type would you say to use? What dose would you try it for two weeks and then take a break? What would you recommend?

Well, first of all, I will say what I say to everybody who sends me an email about this, which is do this with a doctor, under a doctor's supervision or with a doctor. If you think you might benefit from it, go to your physician or your practitioner and say, look, I think this is reasonable based on XYZ. That being said, I think the lowest, low doses are helpful start even lower than a full patch with a half a patch or even a quarter patch. I think, you know, the effects can be quite unpleasant if you start with a full dose because you and I as non-spo, well, you may be as an ex-smoker may have less sensitivity, but me as a non-smoker or other non-smokers are going to be very sensitive to even small amounts of nicotine in terms of the adverse effects, the side effects. And so I think people should be careful with it. And, um, and, uh, try to be thoughtful in their use, use it for a brief period of time, see if it helps under certain circumstances. But I really do think that it should be done in conjunction with one's clinician. It is a powerful drug. We shouldn't forget that. What is the single biggest misconception

about nicotine that you want to clear up for everybody listening today? I think nicotine is not a poison. It's a drug. It can have toxic effects if it's used at high doses are in the wrong way, but I think there is a potential for therapeutic benefits. And I think that it has to be separated from tobacco. That's the problem. People say, well, nicotine is addictive. Well, actually, by itself, it's really not. And I challenge anyone to show me that nicotine by itself is addictive. It all depends on how it's given and what form it's given and the way it's given. And I think that we need to be able to separate the nicotine from the tobacco.

That's the myth. Amazing. Well, thank you so much, Dr. Newhouse. I really appreciated this conversation. Well, I've enjoyed it. And you've given me a lot to think about, actually, in some of your questions. Because I realize when you ask them how little we still know. about this. Yeah. I honestly love, I feel like one of the ways you can tell if somebody's a real

scientist is if they're willing to say, we don't know, we need to do further research on this. I love being comfortable with asking more questions because that's the core of what science is all about. Right. Beware someone who knows all the answers. 100%. Thank you so much for tuning in to this episode of the Liz Moody podcast. If you enjoyed the episode, go ahead and follow on Apple or Spotify or subscribe on YouTube and hit that notification bell so you never miss a new episode. And if there's somebody in your life you think would benefit from this episode, send them a quick link. It is the best way to support the podcast, and it is so, so appreciated. And if you're watching this, drop me a comment. I would

love to hear your thoughts and what resonated most with you. Thanks again for being here. I feel so lucky that I get to grow and learn and share with you, and I will see you on the next episode of the Liz Moody podcast. Oh, just one more thing. It's the legal language. This podcast presented solely for educational and entertainment purposes. It is not intended as a substitute for the advice of a physician, a psychotherapist, or any other qualified professional.