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The Dose Transcript for February 27, 2025

Host: Dr. Brian Goldman

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BRIAN GOLDMAN: Hi, I'm Doctor Brian Goldman. Welcome to The Dose. Let's begin by saying that cigarette smoking is the main cause of preventable death in developed countries. Smokers use nicotine replacement products to quit tobacco. But lately, I've noticed some talk on social media about never smokers consuming nicotine gums, lozenges, and other products to boost cognition. They're doing so despite studies showing that nicotine is as addictive as cocaine and opioids. So, this week, we're asking: How does nicotine affect cognition, and what's the risk? Hi, Steven. Welcome to The Dose.

STEVEN LAVIOLETTE: Hi, Brian. Thanks for having me.

BRIAN GOLDMAN: If you could design the perfect cognitive enhancer, what would be its defining attributes?

STEVEN LAVIOLETTE: I think the perfect cognitive enhancer would be something that has as least dependance producing ability as possible, something that's not going to get you hooked on it, and it's not going to cause any symptoms of the drawl after you stop taking it.

BRIAN GOLDMAN: I'm assuming that that it doesn't exist.

STEVEN LAVIOLETTE: It does not exist that we're aware of anyways.

BRIAN GOLDMAN: Okay, well, which is why some people are turning to nicotine and why we've got you on the show. But before we begin, can you give us a, "Hi, my name is," tell us what you do, and where you do it.

STEVEN LAVIOLETTE: Sure. My name is Steve Laviolette. I'm a professor of neuroscience at the University of Western Ontario here in London, Ontario.

BRIAN GOLDMAN: Okay, here we go. What do we know about how common it is to use nicotine gums or lozenges to improve cognition?

STEVEN LAVIOLETTE: Unfortunately, we don't have too many hard statistics on that because there is, of course, the compound. A lot of people are using those products to sort of wean themselves off traditional cigarettes or, you know, other forms of tobacco, vaping, that sort of thing. And, you know, it's difficult to sort of draw a line between someone who was using those sorts of, sort of pharmacological nicotine enhancers to prevent the withdrawal from traditional nicotine dependance versus, you know, actually using it as a form of cognitive enhancement.

BRIAN GOLDMAN: Any idea who might be using nicotine for that purpose?

STEVEN LAVIOLETTE: Well, you know, sort of the typical population we think of would be, you know, like university students, college students who need to stay up late for, for an exam or get an assignment done, you know, maybe, maybe high school students and in the later years as well. People under high pressure occupations, people that have to work night shifts, for example, might be looking to some, some form of cognitive enhancement or some way to keep their, keep their minds alert during sort of long hours of work. Those sorts of groups of people would be most likely to be using them.

BRIAN GOLDMAN: What does the research show about how nicotine improves brain function, namely memory and attention? I guess to some extent, executive function?

STEVEN LAVIOLETTE: Well, I'll sort of start at the basics. Nicotine, like a lot of different compounds that, you know, have psychotropic effects, interact with a naturally occurring receptor system in the brain. And this is the nicotinic receptor system. They form this receptor on neurons, and they are excitatory. So, when acetylcholine, which is the brain's natural neurotransmitter that interacts with the nicotinic system, when it binds to the receptor, it opens up and excitatory ions flow into the cell, and it causes what we call depolarization. So, it excites the brain. So, the basic pharmacology of nicotine is that it's exciting these nicotinic receptors, and this causing the stimulatory effect on your nervous system. And because we see high concentrations of these nicotinic receptors in areas of the brain that are responsible for cognition and memory, areas like the frontal cortex or the hippocampus or the thalamus or the amygdala. When you smoke cigarettes or when you vape nicotine or even, you know, chew Nicorette or take a nicotine patch, you're stimulating that excitatory system. You're your stimulating pathway in the brain that has been there for millions of years, to help keep the mind alert and help us with memory and help us with higher order thinking and cognition. And so, it really makes sense from a, from a neurophysiological perspective, that nicotine would be a naturally powerful cognitive enhancer and memory enhancer as well.

BRIAN GOLDMAN: And are these receptors located in in the parts of the brain that we know are involved in learning things like the prefrontal cortex?

STEVEN LAVIOLETTE: Yes, absolutely. So, there's a lot of nicotinic receptors that are found in areas like the frontal cortex. Another area is the thalamus, which is sort of the sensory relay centre of the brain. And so, when you activate nicotinic receptors on the thalamus, you're also going to improve sort of the general baseline of stimulation and sensory processing, that sort of thing. And you know, we've known this for many years, and it's quite common in almost all mammalian brains to have these sorts of nicotinic receptor populations on areas of the brain that are responsible for these sort of cognitive functions.

BRIAN GOLDMAN: And I'm thinking about my neuroanatomy days, the amygdala and the hippocampus would be other parts of the brain that would be, that would be involved, that would have high concentrations of these receptors.

STEVEN LAVIOLETTE: Yeah, absolutely. And of course, the hippocampus is really sort of the, the central processing area for a lot of our memory, all sorts of memories. So, you know, episodic memory, working memory, these are all dependent on the hippocampus. And so, when you're able to sort of stimulate that nicotinic system in areas like background getting has cognition.

BRIAN GOLDMAN: You know, I've been doing health reporting medical stories for decades. And I remember a long time ago, you know, in which we interviewed an expert and that expert said, it's really important to understand when people attempt to quit smoking, what they may be losing or sacrificing by quitting smoking. And this expert said to me that, you know, many smokers say that they think better. If are accountants, they do figures better. They can keep more items or digits in their head when they're smoking. And one of the reasons why they're loath to quit smoking is that they think they're going to lose that cognitive edge. Have you heard that as well?

STEVEN LAVIOLETTE: Yeah, absolutely. And that's sort of a common theme. Again, it goes back to the one of the confounding issues in a lot of that research is that people tend to take those products and also continue smoking as a way of avoiding withdrawal. So, once you've become chronically exposed to nicotine for many years, for example, once you suddenly no longer have access to the nicotine, you immediately go in to say, a withdrawal. And that in and of itself, can cause problems with cognition. So, you have a depressed mood. You have sometimes confused thinking, because this is one of the well-known side effects of drug dependance withdrawal. So, it's critical to be able to tease apart the part in which the nicotine is improving cognitive, cognitive skills by alleviating the withdrawal versus just improving cognition in and of itself. Now, having said that, there's a wide body of evidence suggesting that even as someone that's not necessarily dependent on nicotine and a lot of these, of course, are animal studies as well, we know that if you give nicotine, you can improve memory performance. There's evidence as well that patients with schizophrenia, we know that over 90 per cent of patients with schizophrenia are heavily dependent on tobacco products. And a lot of those patients will report that the nicotine, the tobacco, will improve their cognition because one of the side effects of antipsychotic medication is, you know, a loss of memory, a loss of cognitive function. So, it's a way of counteracting some of the negative side effects of psychiatric medications, for example.

BRIAN GOLDMAN: So, you've mentioned schizophrenia. What about Parkinson's? What about Alzheimer's?

STEVEN LAVIOLETTE: Yeah. So, those are also great examples. So, it was somewhat controversial, it came out a few years ago that, you know, nicotine can have some neuroprotective effects in Parkinson's and also with, with Alzheimer's. And there's, there's, when you when you actually think about the neurophysiology, that makes a lot of sense because what Parkinson's is, is a loss of dopamine neurons. And what happens with Parkinson's patients is that these dopamine neurons start dying off. So, you're getting less dopamine. So, we know that nicotine can hyperstimulate the dopamine system. So, it makes perfect sense that nicotine can counteract some of that pathological, some of those pathological impacts of the, the death of these, these dopamine neurons in patients with Parkinson's. And at the same time, this would also counteract a lot of the other side effects of Parkinson's, like depression and lack of motivation. In the case of Alzheimer's, acetylcholine is the primary neurotransmitter involved in regulating cognition and memory function in the brain. And so naturally, we know that there's a loss of acetylcholine in patients with Alzheimer's. So, again, it links into this importance of this acetylcholine system in the brain, and the fact that nicotine can directly stimulate that system to counteract some of these pathological effects.

BRIAN GOLDMAN: What about people who have ADHD?

STEVEN LAVIOLETTE: Yeah, there's not as much research on that. And there is some evidence to suggest that there may be a dysregulated dopamine system in people with ADHD. So again, you could imagine that nicotine might be able to help sort of normalize dopamine levels, whether they're hyperactive or underactive in ADHD. And that might improve some mental clarity for people with ADHD. Another important impact of nicotine is that it modulates the release of glutamate, which is an excitatory neurotransmitter in the frontal cortex. And we know that patients with ADHD have, have some difficulty with glutamate transmission in areas like their frontal cortex. So, nicotine again might be able to help, you know, regulate some of those abnormal firing patterns in the brain.

BRIAN GOLDMAN: How long lasting would we expect the cognitive boost provided by nicotine to be?

STEVEN LAVIOLETTE: Right. Well, nicotine is a pretty fast-acting drug. It's usually sort of metabolized depending on the dose, of course, about, you know, a couple of hours. The other important thing about the nicotinic system is that those receptors are very easily desensitized. So, as soon as nicotine sort of hits that receptor, you start this desensitization process. And so, the receptors sort of shut down for a while. They could even become internalized inside them, inside the cell. So, you can get these desensitization and internalization, internalization effects following chronic exposure of nicotine. That can also mean that you're going to get tolerance, you're gonna need higher doses of nicotine to, to achieve the same effect.

BRIAN GOLDMAN: Of course, there are many ways to ingest nicotine. You know, we're talking about gums and lozenges and patches. You know, smokers inhale nicotine. And so, it passes directly from the lungs to the brain. Is there a difference in how long we would expect the nicotine to last, depending on, on how you ingest it?

STEVEN LAVIOLETTE: Well, that's right. I mean, smoking is going to be sort of the first hit that get right, gets right to the brain. If you're ingesting it, well, oral ingestion, such as the nicotine gum or even chewing tobacco, that gets into the bloodstream pretty quickly as well.

BRIAN GOLDMAN: Got it. Okay.

STEVEN LAVIOLETTE: And of course, the patch as well. So, that's going into the skin. That's going to take a bit longer because it has to go through all the subcutaneous fat and that it has, you know, different metabolic routes and that sort of thing. But you know, vaping and smoking are so certainly the fastest route to get to the brain.

BRIAN GOLDMAN: You've started to talk about this, but I want to move into the subject of addiction. We know that nicotine is highly addictive. What is it about nicotine and its effects on the brain that make it so highly addictive?

STEVEN LAVIOLETTE: Well, a lot of the evidence has suggested that once you start being exposed to nicotine for extended period of time, you get this very rapid sensitization of the dopamine system. So, the dopamine system is a complex pathway. It's not just involved in addiction or reward. It's involved in a lot of different emotional and motivated behaviours. But what we do know is that once you're exposed to nicotine over extended period of time, you get this long-term sensitization of the dopamine pathway. So, we've done studies where we've looked at chronic nicotine exposure. And what we found was that after just seven days of chronic exposure to nicotine, the brain's dopamine system is greatly sensitized to subsequent nicotine. So, nicotine after subsequent exposure causes like this hyperactivation of the brain, of the dopamine neurons that we've seen before. We've also more recently been looking at the impacts of neural developmental nicotine exposures. So, we give exposure to nicotine during adolescence. And what we found is that again, you have this hyperactive dopamine system, the lasts all the way into early adulthood. And if the dopamine system is overactive, it's going to be more responsive to subsequent drugs, drugs. And most, and most drugs that produce dependance interact with the dopamine system in one way or another. So, in that sense, it's certainly possible that chronic exposure to nicotine is sort of setting the stage for increased vulnerability to exposure to dependance from other substances that activate the dopamine system.

BRIAN GOLDMAN: Steven, what do you mean by sensitization?

STEVEN LAVIOLETTE: Well, sensitization is sort of the opposite of tolerance. So, rather than needing more and more, what happens is that over time, the system becomes hypersensitized to the same dose. So, for example, if we were to use this as an animal model, let's say we begin with 0.1 milligrams of nicotine injected into our rat, for example, on day one. By day 10, that same dose of nicotine is going to have a much stronger impact on, for example, the brain's dopamine system than on day one because the systems keeps ramping up. And that's why we use the word sensitized. It becomes more sensitive over time with repeated exposure to the same drug.

BRIAN GOLDMAN: And what impact would that have on the user? Now we're talking about a human being, not a rat.

STEVEN LAVIOLETTE: Well, it sort of depends. I mean, everyone's a little bit different and it depends on the exposure route, the frequency of exposure. In some cases, if you get a hyperactive dopamine system, you're going to be agitated, you're going to, you're going to have increased anxiety, loss of cognitive control, possibly memory problems. If the dosing is less intense, then it would be a much more subtle response. But you'd probably experience withdrawal as well from the nicotine over time.

BRIAN GOLDMAN: Wow. Now we've, you know, I think we're talking about smokers, but how does the risk of addiction to nicotine gums and puffers compare to nicotine cigarettes?

STEVEN LAVIOLETTE: Yeah. No, it's a great question. And there's, there's not too much research out there that's directly compared, you know, smoking or vaping versus people on the patch. There's no reason to suspect that they would be hugely different. So, I would expect that the, the ability to produce dependance and withdrawal would be faster with vaping and smoking, but the risk of dependance withdrawal would be very similar. Whether you're chewing Nicorette gum or whether you're using a patch, ultimately, it's going to have the same effect.

BRIAN GOLDMAN: You know, I, Stephen, I was shocked to see one paper on PubMed that was a case report of five individuals who were consuming nicotine gum. These were never smokers who were using it recreationally. It was a documentation of their addiction, of their dependance on nicotine gum. Compare that to many, many, many studies of nicotine gums and other nicotine replacement therapy use in smokers. Yeah, it seems as if there's a gap there in research that probably needs to be filled.

STEVEN LAVIOLETTE: Oh, absolutely. Yeah. I mean, there's a lot of gaps in the nicotine addiction literature. With the rise of e-cigarettes and vaping, for example, there's actually very, very few large-scale studies either directly compared vaping, sort of more purified forms of nicotine versus traditional tobacco cigarettes. You know, we don't even know too much about that in terms of the differences. So, there's a big gap in the literature that really needs to be filled and improve our understanding those differences.

BRIAN GOLDMAN: So, in your opinion, how risky is it for a never-smoker to start using nicotine gums and other forms of replacement?

STEVEN LAVIOLETTE: I think it's quite risky. Especially, and we now, we now know with a lot of genomic studies that there are definitely certain individuals with genetic predispositions to be more likely to get dependent on nicotine. But of course, if you don't have that information, you don't really know. So ultimately, you're taking a chance. And you know, at the end of the day, you don't really want to find yourself dependent on any substance that is going to cause distress if you decide to go off the substance.

BRIAN GOLDMAN: And, you know, one of the reasons why we're doing this is because we're hearing that there are people who are using nicotine recreationally. The other reason is that a few days ago, I, you know, I walked into a pharmacy and, and there, you know, in front of the dispensary, not behind the counter, but in front of the dispensary were all manner of nicotine replacement therapy products. You could just walk up there and buy whatever you want. So, you know, that, that kind of implies that it's safe when it's not. So, so thinking about that, Stephen, what's your advice that you want to give people who are listening to this conversation now, considering that some of them may be hearing about this and may be tempted to walk into a pharmacy and just pick up some nicotine replacement and start using it?

STEVEN LAVIOLETTE: Right. That's an excellent point. And you know, I would add to that also that, you know, the vaping industry is largely unregulated as well. I mean, you can go in and pick up nicotine vaping pods with relative ease. But my advice would be just, you know, avoid it. There's not enough research into this at this point. And there's probably healthier, healthier alternatives to look at. You know, there's a lot of people that are taking nutritional supplements, for example. There's some evidence that even choline, which is the precursor for acetylcholine, may have some pro-cognitive effects as well. And we know that these sorts of nutritional dietary supplements are, they carry very little-known risk associated with them. And they're not going to produce any dependance. So, the long story short is that I think there are, there are far healthier ways to improve your cognition. Safer supplementation, nutritional supplements, dietary changes and of course, exercise as well is probably the safest cognitive enhancement that we can, that we are even aware of right now.

BRIAN GOLDMAN: And while we're talking about risk, the risk is even greater for people who are young enough to still have developing brains.

STEVEN LAVIOLETTE: Yes, absolutely. That's a great point. There's overwhelming evidence that the adolescent brain in particular is highly sensitive to nicotine. And, and a lot of our studies have shown that nicotine really has a toxic effects on the adolescent brain that lasts all the way into adulthood. So, again, especially if you are in that sensitive time of brain development, this is certainly a point in your life where you would want to avoid exposing yourselves to high levels of nicotine.

BRIAN GOLDMAN: So, some good advice and some precautions to consider. Professor Steven Laviolette, thank you so much for speaking with us.

STEVEN LAVIOLETTE: Thanks very much for having me.

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BRIAN GOLDMAN: Stephen Laviolette is a professor in the School of Medicine at Western University. His research focuses on neuropsychiatric disorders, including addiction and schizophrenia. Here's your Dose of smart advice. Nicotine enhances cognition. That's been shown in animal studies and in human clinical trials. Nicotine can boost attention, working memory and fine motor skills. It can regulate cognition and improve executive function. The parts of the brain where nicotine acts to improve cognition include the hippocampus, amygdala, and prefrontal cortex. The effects, while measurable, tend to be relatively minor and last an hour or two. Unfortunately, nicotine is also addictive, something we know from studies of smokers. Nicotine activates receptors on dopamine cells in the brain, which causes a dopamine rush. Repeated consumption of nicotine over time leads to increased cravings and withdrawal symptoms that lead to more and more nicotine use. Withdrawal can include irritability, anxiety, and difficulty concentrating. Nicotine replacement products help smokers quit tobacco by replacing cigarettes with a safer form of nicotine. There is very little clinical research on how these products affect people who never smoked. If you use those products often enough and at a high enough dose, it's likely that sooner or later you will become addicted to them. The risk to teens and to young adults with developing brains is even greater. The fact that nicotine replacement products are readily available without prescription means non-smokers might be tempted to give those products a try. You need to weigh the relatively short-term cognitive benefits against the risk of long-term addiction. If you have topics you'd like discussed, or questions answered, our e-mail address is: thedose@cbc.ca. If you like this episode, please give us a rating and review wherever you get your podcasts. This edition of The Dose was produced by Sameer Chhabra. Our Senior Producer is Colleen Ross. The Dose wants you to be better informed about your health. If you're looking for medical advice, see your health care provider. I'm Doctor Brian Goldman. Until your next Dose.

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How does nicotine affect cognition and what's the risk? - Transcript

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