Deep Dive
Shownotes Transcript
When a body is discovered 10 miles out to sea, it sparks a mind-blowing police investigation. There's a man living in this address in the name of deceased. He's one of the most wanted men in the world. This isn't really happening. Officers finding large sums of money. It's a tale of murder, skullduggery and international intrigue. So who really is he?
I'm Sam Mullins, and this is Sea of Lies from CBC's Uncover, available now. This is a CBC Podcast. Hi, I'm Dr. 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, Stephen. Welcome to The Dose. Hi, Brian. Thanks for having me. If you could design the perfect cognitive enhancer, what would be its defining attributes? I think the perfect cognitive enhancer would be something that has as least dependence-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 withdrawal after you stop taking it. I'm assuming that it doesn't exist. It does not exist, that we're aware of, anyways.
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. Sure. My name is Steve Laviolette. I'm a professor of neuroscience at the University of Western Ontario here in London, Ontario. Okay, here we go.
What do we know about how common it is to use nicotine gums or lozenges to improve cognition? Unfortunately, we don't have too many hard statistics on that because there's, of course, the confound. 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 is using those sorts of sort of pharmacological nicotine enhancers to prevent the withdrawal from traditional nicotine dependence versus, you know, actually using it as a form of cognitive enhancement. Any idea who might be using nicotine for that purpose?
Well, you know, sort of the typical population we'd think of would be, you know, like university students, college students who need to stay up late for an exam or get an assignment done. You know, maybe high school students 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 form of cognitive enhancement or some way to 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.
What does the research show about how nicotine improves brain function, namely memory and attention, I guess, to some extent, executive function? Well, it sort of started the basics. Nicotine, like a lot of different compounds that have psychotropic effects, they 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 a depolarization. So it excites the brain. So the basic pharmacology of nicotine is that it's exciting these nicotinic receptors and is causing the stimulatory effect on your nervous system.
And because we see high concentrations of these nicotinib 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 we vape nicotine or even, you know, chew Nicorette or take a nicotine patch, you're stimulating that excitatory system. You're stimulating a 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 neurophysiological perspective that nicotine would be a naturally powerful cognitive enhancer and memory enhancer as well. And are these receptors...
located in the parts of the brain that we know are involved in learning, things like the prefrontal cortex? Yes, absolutely. So there's a lot of nicotinib receptors that are found in areas like the frontal cortex. Another area is the thalamus, which is sort of the sensory relay center of the brain. And so when you activate nicotinib 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.
And I'm thinking about my neuroanatomy days, the amygdala and the hippocampus would be other parts of the brain that would be involved, that would have high concentrations of these receptors. Yeah, absolutely. And of course, the hippocampus is really sort of the central processing area for a lot of our memory, all sorts of memory. 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 that you're going to get enhanced cognition. 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's
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 they're 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 loathe to quit smoking is that they think they're going to lose that cognitive edge. Have you heard that as well?
Yeah, absolutely. And that's sort of a common theme. Again, it goes back to 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 into a state of 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 dependence withdrawal. So it's critical to be able to tease apart the part in which the nicotine is...
improving 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% 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.
So you've mentioned schizophrenia. What about Parkinson's? What about Alzheimer's? Yeah, so those are also great examples. So it was somewhat controversial or came out a few years ago that, you know, nicotine can have some neuroprotective effects in Parkinson's and also with Alzheimer's. And 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 those pathological impacts of the death of 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.
What about people who have ADHD? Yeah, there's not as much research on that. There is some evidence that suggests 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
improves 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 some difficulty with glutamate transmission in areas like their frontal cortex. So nicotine, again, might be able to help regulate some of those abnormal firing patterns in the brain. How long lasting would we expect the cognitive boost provided by nicotine to be?
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 can even become internalized inside the cell.
So you can get these desensitization and internalization effects following chronic exposure to nicotine that can also mean that you're going to get tolerance. You're going to need higher doses of nicotine to achieve the same effect. A random influencer, a friend who read something somewhere, your doctor. It can be hard to know where to get trusted health information.
TED Health is a podcast that will help you focus on the stuff that you actually need to know to live your healthiest life. I'm Dr. Shoshana Ungerleider, a practicing internist, and I share weekly TED Talks from certified health experts that break down the questions you're always getting different answers to. Get the science-backed ideas for a healthier you with TED Health, wherever you get your podcasts.
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?
Well, that's right. I mean, smoking is going to be sort of the first hit that 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. Aha. Got it. Okay. 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 then 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.
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? Well, a lot of the evidence has suggested that once you start being exposed to nicotine for an 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 behaviors. But what we do know is that once you're exposed to nicotine over an 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 neurodevelopmental nicotine exposure. So we give exposure to nicotine during adolescence. And what we found is that, again, you have this hyperactive dopamine system that lasts all the way into early adulthood.
And if the dopamine system is overactive, it's going to be more responsive to subsequent drugs. And most drugs that produce dependence 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 dependence from other substances that activate the dopamine system. Stephen, what do you mean by sensitization? 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 dopes.
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 a 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 system 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. And what impact would that have on the user? Now we're talking about a human being, not a rat. 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 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. Wow. Now, I think we're talking about smokers, but how does the risk of addiction to nicotine gums and puffers compare to nicotine cigarettes? Yeah, no, it's a great question. And there's not too much research out there that's directly compared 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 ability to produce dependence and withdrawal would be faster with vaping and smoking. But the risk of dependence 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. You know, 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 dependence on nicotine gum. Compare that to many, many, many studies of nicotine gums and other nicotine replacement therapy use in smokers. It seems as if there's a gap there in research that probably needs to be filled.
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 few large-scale studies that are 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 of those differences. So in your opinion, how risky is it for a never smoker to start using nicotine gums and other forms of replacement? I think it's quite risky, especially, and 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. 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, you know, I walked into a pharmacy 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 kind of implies that it's safe when it's not. 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? 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 online.
with relative ease. But my advice would be just avoid it. There's not enough research into this at this point. And there's probably healthier alternatives to look at. 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, they carry very little known risk associated with them, and they're not going to produce any dependence. So the long story short is that I think 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 are even aware of right now. And while we're talking about risk, the risk is even greater for people who are young enough to still have developing brains.
Yes, absolutely. That's a great point. There's overwhelming evidence that the adolescent brain in particular is highly sensitive to nicotine. And a lot of our studies have shown that nicotine really has toxic effects on the adolescent brain that lasts all the way into adulthood. So again, especially if you are in a 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. So some good advice and some precautions to consider. Professor Stephen Laviolette, thank you so much for speaking with us. Thanks very much for having me. Stephen Laviolette is a professor in the Schulich School of Medicine at Western University. His research focuses on neuropsychiatric disorders, including addiction and schizophrenia.
Here's a 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 email address is thedoseatcbc.ca. If you liked this episode, please give us a rating and review wherever you get your podcasts. This edition of The Dose was produced by Samir 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 Dr. Brian Goldman. Until your next dose. For more CBC podcasts, go to cbc.ca slash podcasts.