Chapter 1: The fears around vaping
Hi, I’m Wendy Zukerman and you’re listening to Science Vs. This is the show that pits facts against fumes. On today’s show: Vaping…
Before we get any further, I need to introduce you to our first guest.
NO: Hello, my name's Nina Oyama. I'm a comedian, writer, actress, an inspirational vapress.
This inspirational vapress first started vaping several years ago when she was in the US
[MUSIC IN]
NO: I was in Los Angeles and somebody gave me a vape there and it was just so much yummier than the Sydney ones at the time. Like, you know how there's different flavors? Um, in Sydney there was mostly just like, you know, pineapple or like berry or whatever, but in Los Angeles they had like, Lush ice and like aloe vera mango sorbet ice…that were quite enjoyable
WZ: What did it feel like in your mouth?
NO: Um, it just like felt like a flavoured puff of smoke
[MUSIC OUT]
So Nina got into vaping. She used to smoke ciggies but the hangovers after a night of drinking and smoking just got too nasty. With vapes, she says, it's nice to have something in your hand. It's fun to pass them around at parties.
And some people get a head rush.
NO: My partner is like, oh, I do it for the head rush. And i'm like, I don't even get a head rush. Like I do it. I think it's really funny. Like if you are in a conversation and say something really dumb – and then you punctuate a bad joke by blowing a vape or like WZ: Wait, Of how like a vape could punctuate a joke.
NO: I don't know like if you say something stupid and then you just kind of raise your eyebrows and like blow vape out of your mouth - I don’t have anything that's coming to mind currently… There's just a lot of fun stuff you can do with vapes
And there’s a lot of people doing stuff with vapes[1][2][3], particularly kids - about 1 in 10 middle and high school kids are vaping, that's according to the FDA and CDC.[4][5] And us adults, we’re doing it too..
NO: Yeah, it's everywhere. We actually would say most of my friends dabble, at least.
WZ: Have you ever worried about the health effects of vaping?.
Be honest.
NO: Nah.
WZ: Nah?
NO: No! Like vapes are vegan right?? Like, vapes are vegan!
Ok but jokes aside… a lot of people are worried about vapes... Governments, Health Officials… We're hearing that this is actually a crisis… an epidemic amongst our youth… [6][7][8]
WZ: Do you want to hear some scary news reports about vapes?
NO: Yeah, let's learn about vapes.
[MUSIC IN]
NEWS CLIPS
Vaping could be more dangerous than first thought
Kids don't know just how bad it is for them
Concerned parents one of their classmates taken to hospital after vaping
Teens who vape are more likely to report symptoms of depression and anxiety
Once you get it you want it more and more and more
Today on the show… how dangerous are vapes really? It felt like for years scientists were just grappling with what vapes were doing to our brains and bodies. But we are finally getting some answers.
[MUSIC OUT]
When it comes to vaping, luckily, there's lots of...
NO: yeah let's learn about vapes
And then there’s science.
AHHHH
Science Vs Vaping is coming up… after the break.
PREROLL BREAK
Chapter 2: Could vaping make you sick? [03:41]
Welcome back. Today on the show, Vapes or E-Cigarettes…
WZ: comedian and vapress. High vapress, is that what we decided to call you? Nina Oyama is joining us as well. Hey, Nina.
NO: Hello
OK so for the uninitiated….vapes are battery-powered devices that heat up a liquid, turning it into an aerosol that you can inhale.[9] So actually what you are inhaling is, is an aerosol. So they should be called aerosolers.
WZ: Did you know this? You're not actually breathing in vapor.
NO: Oh, so it's like a deodorant.
WZ: I mean you could think about it like that because vapor is just a gas, but an aerosol is like little particles inside a gas like little bits of crap[10][11]
NO: Oh wow
WZ: which is what is in a vape…but obviously vape sounds cooler than aerosol.
NO: Yeah Love that.
So they were introduced more than a decade ago[12] in the hopes that they would help people quit smoking[13] and that they would be safe.[14] But, to find out if that's true, we called up, is Dr. Michael Chaiton. He's a senior scientist at the Centre for Addiction and Mental Health in Toronto, Canada.[15]
WZ: Have you, have you tried a vape?
MC: Yeah, so I've definitely tried vaping. It's, you know, just to, you want to be able to see what it's like. Certainly in the ’90s when I was a teenager, I was also, tried cigarettes as well. It's new, it's novel. It's like, what is this, exactly?
WZ: So Michael, scientist, but just like us!
NO: I don't know man, he sounds like a nerd.
WZ: Pfft, okay, I snorted! You just made me snort! No nerds around here - wouldn’t know them. Never met them. So…
NO: nah man.
So one of the big fears around vaping has always been that you're breathing crap into your lungs… and that it could damage them…. But for a long time, we didn't really know if this was a big issue or not. So Michael did this study[16] to find out. It started with some ads on Facebook and Instagram.
WZ: in your paper, um, it just notes that you recruited, uh, the people in your study via social media. How are you trying to capture the youth?
MC: one of our earlier studies, … we were doing research on food and, uh, we just put…disgusting pictures of food….like gross close ups of, of meat. And, you know, it's like… one weird trick to, uh, you know, understand, uh, your food habits
WZ: And it was like, fill out this survey. That's the weird trick?
MC: Yeah, fill out the survey. Exactly. Exactly. The ethics, the ethics board was, uh, uh, it was, you know, it was encouraging us to be more boring, but, uh, um, you know…
WZ: Not such a nerd now.
NO: laugh
Okay, so he just did this boring ad over over Facebook and Instagram saying like can you fill out this survey about vaping… just over 3,000 people took the bait.
[MUSIC IN]
They were between 16 and 25. Some of them were ciggy smokers, others stuck to vaping, some used both. And they answered questions like, “When you vape, how many puffs do you take?”... “How old were you when you first tried vaping?” And then he also asked them questions about their health.[17]
MC: Whether they were coughing or wheezing…or they had…colds regularly…difficulty breathing
Other questions were like, were they coughing up phlegm regularly? Did they have, um, shortness of breath, like did they run out of breath from simple chores?
WZ: Nina, how would you have answered any of those questions?
NO: Um, yeah, I think I pretty much do have a cold all the time.
WZ: Really?
NO: Yeah, but do you think that's from vapes? Or do you think that's... From something else.
WZ: Just asking questions.
[MUSIC OUT]
So, in Michael's study, he checked in and asked people these questions every three months for up to a year. And he saw a very clear trend: for the people who vaped,[18] the more puffs they took, on average, the more likely they were to have some respiratory symptoms. Stuff like a cough, coughing up phlegm.[19] Which to Michael, he said, was worrying, particularly considering how young the people in his study were.
MC: If you think about, like, a 19 year old who's complaining of wheezing…that's not a normal thing…you know, that, that having a sort of a, a chronic cough also, it's, that's not a normal thing either. And that’s what these youth were reporting.
It’s not just Michael’s study that’s found this … other research is picking up similar things… yknow seeing that vapers have higher rates of wheezing compared to non-vapers.[20][21][22][23]
Now a lot of the symptoms in Michael's study, they weren't that scary - no one likes a cough, but you can deal with it…. But Michael is worried about what happens next – because his study was only for a year or so[24]... and Michael says that from other research that we know, respiratory symptoms are often the starting place….
MC: You know so I think respiratory symptoms are one of the canaries in the coal mine[25]
And so one of the things he's worried about is this lung disease that you see with cigarette smoking, which is called chronic obstructive pulmonary disease, or COPD.
WZ: What, what is it? What, what happens?
MC: Just can't breathe. You can't breathe. And so probably if you've seen people go around with oxygen tanks, um, it is, that's, that's likely COPD.[26]
NO: Uh huh
SO this is where we start getting into, like, scaremongery land. But COPD kicks in when your lungs are really screwed. We know it is linked to cigarette smoking.[27] We are already seeing some data that it is like, vaping ups your chance of getting it, also increases your risk of asthma.[28]
NO: Damn.
WZ: But obviously, early days here.
NO: Yeah.
And also, not everyone in Michael’s study said they had symptoms on his survey. In fact, about one-third of the people who vaped daily, and stayed off ciggies, had none of the respiratory stuff he was talking about.[29] One third.
NO: Mmm
Chapter 3: Are vape flavors dangerous? [09:45]
So our next question is, what is it about vapes that's causing these symptoms? Uh, because one culprit... That's been getting a lot of attention[30][31][32][33] are flavors.[34][35]
NO: Not my lush ice! No, don't take away my lush ice! It's like the best bit of vaping.
Well so then you won't be surprised to hear then that one survey showed that 85 percent of kids who vape are using vape flavors.[36] But, in crackdowns around the world, governments, including here in Australia,[37] are trying to ban flavors. So, let's look into the science. Are flavors really the bad guys here? To know that, we have to take a trip to Flavortown.
NO: Oh yeah, flavor country.
[FLAVORTOWN SFX]
Um, and our tour guide is Ilona Jaspers.[38] We spoke to her a few years ago. She's an inhalation toxicologist and professor at UNC Chapel Hill in North Carolina. And she studies flavors in vapes.
WZ: If we were going to do a personality quiz… that was asking what vape flavor are you? What vape flavor would you be?
IJ: I love meat products, I love blood sausage, I love baloney, probably say I would be one of those
NO: That's freaking gross, man. Imagine hitting like a meat flavored vape
So Ilona told us that one way to find out if these flavors are safe, whether it's your blood sausage or mango, is you have to know what's in them. So we asked her about a very popular Flavor. Mango…
WZ: You’re a kid, you’re thinking like they boil up a mango and save the essence of it.
IJ: Yeah, well I can guarantee you that is not the case. You’re making a different mixture of chemicals that basically then taste like mango. The food industry does this all the time.
Yeah, so just like your favorite ice creams and sodas, these vapes are all flavored with like this hodgepodge of flavor chemicals.
NO: Oh yeah, duh. I don't think it's a strawberry that's for sure
No… They use stuff like cinnamaldehyde, benzaldehyde, and isoamyl acetate,[39] which is rebranded as Cinnamon, cherry almond, and banana.
NO: Oh, delicious.
WZ: So a lot of this stuff had been approved for use in food – but what's safe to put in your gob isn’t necessarily safe for our lungs – so for example, Nina— have you heard of popcorn lung?
NO: Yes. Doesn't your lung, I don't know, get little growths on it like popcorn?
WZ: Do you know when I heard this, that is exactly what was going on, but it’s not so…[40]
[MUSIC IN]
Our story of popcorn lung begins with a chemical called diacetyl,[41][42] which is used to give things like popcorn and vapes a buttery flavour.[43][44][45][46] So here's Ilona.
IJ That's always our example as to why something that's perfectly safe to eat is not perfectly safe to inhale.
So as far as we know, diacetyl is fine to eat,[47] you can keep eating your popcorn - but two decades ago, a bunch of workers in a popcorn factory inhaled this stuff in very high doses and they got really serious lung injuries. A few even needed a lung transplant.[48] And back in 2015, uh, there was a case report of someone who used vapes that had diacetyl in it and it damaged his lungs.[49][50]
[MUSIC OUT]
So, that's just the example that researchers use to say, like, just cause something's safe to eat, it doesn't mean it's safe to inhale.[51]
Which makes a lot of sense when you think about it because the stuff that you eat goes into your stomach and is hit by acids in your stomach ….gets broken down, filtered out, all that good stuff[52][53] — but that stuff doesn’t happen with your lungs—they don’t get that industrial-style cleaning.
IJ: Yeah, so the lung is really not well equipped to detoxify. The lung is really there to take oxygen in and CO2, carbon dioxide, back out.
So this popcorn lung… it portends trouble for the other flavors, but science being science…. You have to test each flavor because it has its own concoction of chemicals[54]. And this is what Ilona does. She tests flavors one by one…she’ll put them on little plates, like Petri dishes. And one of the first, uh, flavors that she looked at was cinnamon…
IJ: We basically took different, uh, cinnamaldehyde containing e-liquids and just put it in a Petri dish and walked away for, for two and a half hours. And it corroded the plastic.[55]
WZ: Wait the flavoring...in cinnamon corroded plastic??
IJ: Yes. Yes it did. Yes. it did. Yes. If this is what it does to plastic … it's probably not going to be good to inhale this into your lungs
NO: Well, I have one question, which is who is, who is smoking cinnamon flavored vapes? And what is wrong with you?
WZ: Ninaaa!
NO: I like that instead of me being like, This is very concerning as it's a result of vape flavoring, And I'm like, It's not even my flavor. That sounds gross.
WZ: I think you've gotten the right message from this
NO: I think I'm listening pretty well.
[MUSIC FADE IN]
To see if this cinnamon flavour does anything for human lung cells, Ilona got a dish, doused it with cinnamaldehyde, And then put little human lung cells into the dish. And she found that it affected these bits of the cells called the cilia. So cilia are like little hairlike structures that help sweep gunk away in your lungs.[56]
IJ One of the things we saw was that the cinnamaldehyde completely abolishes the cilia from actually working the way they’re designed to work.
And so if that's happening in human lungs … it could make it harder for us to clear away the gunk in our respiratory tract.
Now in a different group of experiments,[57] Ilona put immune cells on a petri dish. So this is actually really cool. If you take immune cells out of a body and then put them with bacteria in a petri dish, the immune cells will still work, they will still gobble up that bacteria.
[MUSIC OUT]
But, Ilona found that if you add that cinnamon flavor into this mix …
IJ When we expose it to Cinnamaldehyde we see it can no longer do that[58]
She's seen similar stuff with vanilla flavor.[59] We don't know yet if this stuff is happening inside a human body, inside your lungs, because all of these studies that Ilona does are in stuff like petri dishes.[60] but the fact that we don't know what they're doing inside a human body - that is very frustrating for Ilona.
IJ when you have a new product the safety testing is first done in the petri test and mice, and if that fails it never makes it into a human.
WZ Wait, but that's bonkers cause in this case everyone's … like tried it already and now you're back tracking
IJ I know, I know…It is kind of wild…
WZ: And you know, it's not just the flavors that might be mucking up your lungs.[61][62] There are other chemicals that scientists are worried about.[63]
NO: Wait, there are more chemicals?
WZ: Yes
uh, and a big one[64] is called propylene glycol.[65]
WZ: So this is the chemical that's used in those machines in clubs and on theatre stages to make it look like smoke…
NO: Oh, like a, like a fog machine.[66]
WZ: Yes, that, so that is, that is propylene glycol. [67]
NO So it really is a tiny smoke machine?
WZ: Yeah yeah
NO: That's wild.
WZ: It is cool as a chemical. But when people breathe it in, it has been shown to cause some respiratory symptoms.[68][69]
And I think zooming out – so we don't go through all of the chemicals one by one, I mean for a lot of the stuff you end up sucking in when you suck on a vape…it’s these teeny tiny particles. That bounce around in your delicate lungs, like teeny tiny wrecking balls – causing damage- causing stuff like inflammation. And in fact one study just came out - it was just a small study -but they actually found more inflammation in the lungs of vapers than cigarette smokers.[70] So in general here's how Michael thinks about vapes.
MC: It's like breathing in really small pieces of dirt Like the, the particles themselves are essentially, you know, like small pieces of dirt. You can imagine them in that way tiny grains of sand, uh, that are, are entering your lungs and uh, and potentially damaging them
NO: Huh
WZ: How are you feeling, by the way, with all that lung talk? I mean, was any of it surprising?
NO: Um, it's like, I have always suspected that vapes are bad for me, and um, now I just know a little bit more about why that's true, I guess.
[MUSIC IN]
WZ: And what do you think about the immune system stuff? Does that make you wonder about all those cold symptoms you've been having?
NO: Yeah. Well, that actually makes sense to me. Maybe it's the vape use. Ooh, spooky. WZ: Oooh Science.
Okay, so that is our lungs, but with vapes, some scientists are worried about something else altogether. How vapes could be messing with your brain.
[MUSIC OUT]
And that’s coming up after the break.
BREAK
Chapter 4: Nicotine and depression [20:17]
Welcome back. We just looked into the science about what vaping might be doing to your lungs…and now we’re moving north to what vaping is doing to your brain.
With us is comedian and high empress of vaping - Nina Oyama.
WZ: Hey Nina
NO: Hello!
To find out if vapes are screwing with your brain, we called up Melissa Herman— Associate Professor in Pharmacology at UNC Chapel Hill.[71] And before we dove into the science I had to ask her this burning question of mine ...
WZ: I saw a video on your Twitter of an elf in your lab fridge.[72] Uh, can you explain what was going on there?
MH: Yes, that is Rigsby. Uh, he's our holiday elf. Uh, the lab members position him around the holidays doing different scientific things. Uh, his name is from… uh, an electrophysiological recording rig, which is our favorite piece of equipment in the lab. Um, but he has dabbled in immunohistochemistry. I don't think he's been in our vape chambers, but maybe that's for next year.
Okay, there's one chemical that Melissa is studying in her vape chamber, above all else, and it's nicotine.
NO: Yeah.
So, for a long time, people thought nicotine was pretty safe. It's addictive, of course.[73][74] It's the thing that makes you want to keep vaping. But that doesn’t mean it’s dangerous necessarily. But just to start I asked Melissa about the amount of nicotine in vapes.
WZ: as a general rule, if I took like your average vape, versus your average cigarette, puffed each of them….which one would give me more nicotine?
WZ: Oh really?
MH: By far. Yes. Yes.
MH: And there are companies that are actually designing it with that in mind.
WZ: Oh, of course! This is a huge benefit, right? I mean…that’s why they’re putting all this nicotine[77][78] in there, right? So that we keep using their products.
MH: Yes[79]
Yes, so vapes can have a lot of nicotine in them. And studies have found that you can't really trust what's on the packet to know just how much.[80] So some studies have looked at vape products that were labeled as nicotine-free and found nicotine in some of them.[81][82][83]
NO: That’s terrible!
And Melissa is worried about this. Yes, because nicotine is addictive,
[MUSIC IN]
but also because of this pattern we’ve been documenting since the 1980s, and it’s this, it’s this link between depression and nicotine.
So we started seeing that people with depression were more likely to be smokers, and people who smoked were more likely to later be diagnosed with depression.[84][85][86][87][88] And we're actually seeing the same pattern with vapes[89][90][91][92][93] — so vapers are more likely to be diagnosed with depression and to even have suicidal thoughts, compared to people who don’t vape.[94]
[MUSIC OUT]
WZ: Is this something that you've been worried about or your friends have talked about? I guess I was never aware of this link before.
NO: I was not either. I think that I have had a pretty rocky mental health consistently. Like, I think... especially when I was younger, I was like so depressed. Like I dropped out of school because I was like too depressed to function. Like I flunked the first year of uni because like I couldn't get out of bed. Like I was pretty much in the wars, um, well before I started smoking cigarettes. And so I kind of, um, obviously like this is just my personal journey, but I personally don't think smoking cigarettes or vaping has made my mental health worse because it's only gotten better since I was a teenager.
WZ: I mean I think for researchers in this space who are seeing that connection, there's always been this question of whether the ciggies or the nicotine caused the depression or whether people who were feeling crappy then started smoking.
NO: Yeah.
WZ: I mean even if you just think of that cliche of a ’90s teen smoker… yknow tough baddies sneaking a ciggy behind the high school gym...I guess how many of those kids were already depressed, or were already going to develop depression....and then picked up a cigarette to cope[95][96][97][98][99][100][101][102]
And so Melissa actually tries to use rodents, like mice, to study this[103]
MH: I don't work with humans, I work with preclinical rodent models because they're free of all the cultural baggage… expectation…they don't, rodents don't have any understanding of the ’90s. They don't, like, none of that culture comes into play. It's just biology.
NO: That's funny. That's like, yeah, they just don't, they don't remember like when Britney Spears had free will.
Exactly! So Melissa uses rodents to try to get at this question of whether nicotine might be contributing to people’s depression[104]…or if we’ve just kind of got correlation and causation all mixed up. Now interestingly, with using rodents and cigarettes to try to answer this question….that is difficult partly because of this fun fact about rodents.[105]
MH: You don't see rats or mice voluntarily smoking cigarettes. They won't do that because they understand smoke is toxic…. So they would do everything they could to get away from it….Humans had no problem.
NO: hahah
Yeah. so rodents don't smoke – but they will vape. Now they don't hold a vape. They don't have the little, the little like handsies to hold a vape. So this is where the vape chambers come into it. She has mice in plastic boxes, and then on one side of the box, there's this little hole, and then if the mice poke their nose into that hole, it triggers a release of the vape and oh boy, oh boy, do they love it.
MH: they literally will go over to the hole and very, very intentionally just, mm,
WZ: Okay, so here's where the video that I sent you comes in. Do you wanna, you wanna see it right?
NO: Oh yeah!
NO: Dude, they're like hotboxing these rats with vape juice.
WZ: Oh my god, that is exactly! And so using these chambers, Melissa has been seeing what it does to the mousy brains.
NO: Oh yeah.
Like there’s one study she did with male mice[108] and she gave them these clouds of vape once a day for five days. And then her team dressed up the mice like Mickey Mouse and they all sang together.
NO: Wait.
WZ: No, they, they killed them and sliced up their brains instead.[109]
NO: Oh. Okay, you know, you've just said that I just watched some rats vape and so I was like, you know what, that's completely plausible.
WZ: I didn't, I didn't know if the joke would land given the context, but
NO: you know what would have made that joke way better?? if you had a vape.
WZ: ok haha
So.
[MUSIC IN]
What Melissa has found in these, in these mice is that over time there's this particular area of the brain called the central amygdala
NO: Uh huh
So it does stuff like processes emotions[110][111][112]
Melissa finds that when you give mice nicotine, at first that part of the brain kinda lights up and gets really excited. But after five days on nicotine - that's not what happens. It doesn't react how she'd expect.[113] And Melissa is now wondering if something similar is happening in humans…and whether basically nicotine might be affecting this region of our brain and might be affecting how we process our emotions…
NO: Yeah.
That research is really new, still just in rodents…but there's this other research -that's more established - that suggests that nicotine might be messing with another part of our brain which is called the reward system.[114][115] So basically there's these neurons in a part of our brain that will release dopamine, when you do something nice, like have great sex …
[MUSIC OUT]
WZ: Or umm..smelling a flower, that's nice and G-rated
MH: sure, yes. Very nice, you smell a flower, there's a, there's a spike of dopamine, you'll remember the flower, you feel good about the flower…and most importantly, you encode the idea that that flower smelled good and that that was an enjoyable experience.
Now when you smoke or vape, or get nicotine in your system your brain kind of does something similar.[116][117] That’s why when you take a puff of vape, it might feel good in the moment. So far so good.[118][119][120]
MH: If you, and this is where nicotine and the flower are very different, you smelled the flower, you presumably went on about your day and remembered that that was a nice thing you did. Um, nicotine has immediate actions in the brain … and particularly as people continue administering nicotine, it stays there[121][122][123]
Yeah so if you’re a regular vaper…all that puffing throughout the day would keep nicotine circulating throughout your blood and brain.[124] And it becomes so much for your reward system that it ends up being like WHOA whoa whoa this is too much, this is too much dopamine.[125] Melissa says nicotine is like a speaker blasting music in your brain.
MH: that system is not designed to be switched on and left at full volume.
So from what we can tell - the reward system starts to adapt to this loud noise… [126][127][128] Like, in rodents - the brains will become a little less responsive to nicotine.[129][130][131] Then the idea is that as this happens, you get less dopamine - which could mean you don't get as much enjoyment from smoking, or vaping…as you used to, and maybe other stuff too..
NO: Is it is it just so like when you you know puff on a cigarette…you don't feel as good as you used to as the first time when you puffed on a cigarette? or is that like… when you smell a flower, um, you know, if you've had cigarette use for two years, your flower enjoyment will go down?
WZ Such a good question, some researchers, like Melissa, think that these changes in the brain … could mean you don't get as much enjoyment from the flower, either.[132][133][134][135][136] Now, a lot of the basis for that - that piece in the puzzle - comes from rodent studies – and we're still working out what this means in people.. Because clearly not everyone who vapes ends up getting depression… but we do see that people who vape are more likely to get depression than people who don't vape, and we also know that one of the symptoms of depression is feeling less joy, from things that used to give you joy[137]
So bottom line, when Melissa looks at the evidence and hears people saying nicotine is safe it's just addictive… she's like…
MH: it is not free from concern.
WZ: Yeah, it's not an innocent bystander here.
MH: No!
Chapter 5: Is vaping worse than smoking? [32:03]
Our last question is, does all of this new science around vaping suggest that it is actually worse than cigarettes?
NO: I wanna know.
So for this one, let's go back to Dr Michael Chaiton. So remember he did that study that found that two thirds of people who vaped daily… had some respiratory symptoms? Yeah. Well, in his study… it also captured people who smoked cigarettes…and he found something else in his data…
MC: our first finding was that, uh, cigarettes aren't good for you.
WZ: What?! What?!
MC: so it's, I know it's a shocking finding.
So even though the people in Michael's survey were relatively light smokers, they reported more respiratory symptoms than anyone else, average.[138] So, cigarettes are just so bad for you. One researcher we spoke to described smoking cigarettes as putting your mouth over a car exhaust pipe.
NO: Damn.
Yeah. Estimates reckon that in the US - about a third of the deaths from cancer - are caused by ciggies. One in 3 people who died from cancer - that's from cigarettes. That's huge. [139] Around the world.. we're talking millions of people dying each year.[140][141][142] So even when we say vaping is bad, That doesn't mean it's worse than cigarettes. Here’s Michael:
MC: it's clearly harmful. It clearly has harms. but when you look at it in the context of cigarettes, most people feel that it's very likely to be much safer.
I think after we just spent about half an hour explaining to people the dangers of vaping, we just really need to stamp on this point - that at least according to most of the data out there right now, vaping is still considered better than cigarettes.
NO: Great…So it's healthy!
WZ: DAAA! So, uh, here's my analogy. Smoking cigarettes is like getting run over by a car and dragged for ten miles. So when we say vaping is safer than that.
NO: It's like just getting run over by a car.
WZ: That's right! And you're not dragged for ten miles. Exactly. Exactly.
NO: No, that makes sense.
WZ: Did hearing all the science - did it change—has, are you thinking about vaping differently at all?
NO: I think about it differently - but I'm also like UH! if the question is am I gonna stop - the answer is no
WZ: Does everything we've done together mean nothing to you, Nina??
NO: I can grapple if you want I'll be like... "Yeah, when I - I thought I'd keep vaping, but when I saw my vape sitting on my shelf I threw it in the bin because of the way that it affects my lungs
WZ: Wait, but don't lie!!
NO: WHAT DO YOU WANT FROM ME, WENDY???
WZ: Why wouldn't you quit? Why isn't the science enough to make you or other mates who know the science go— alright, alright I'm done? Is it not bad enough? Is the research too early?
NO I think vapes are bad, But I also think alcohol is bad, and I do think vapes to me are sort of normalised in the way that they are a vice. It's like having a glass of wine with dinner… but for your lungs. And I guess when all this information that’s presented to me is like don't vape - it's like duh…
WZ: If I told you that eating vegetables everyday was actually harmful…
NO: Oh yeah, I'd never eat another vegetable again. But maybe I'm making excuse for myself to keep vaping
WZ Thanks!
NO thank you for having me
That’s Science Vs.
CITATIONS
Science Vs is a Spotify Studios Original. Listen for free on Spotify or wherever you get your podcasts. On Spotify, follow us and tap the bell for episode notifications. And we're also on all the social stuff.. science_vs on Instagram, I’m on TikTok @ wendy zukerman – come say hello!
Credits: This episode was produced by Nick DelRose with help from me, Wendy Zukerman, Joel Werner, Rose Rimler and Michelle Dang. Our original vaping episode was produced by Kaitlyn Sawrey with help from Lexi Krupp and Meryl Horn. Editing by Caitlin Kenney and Blythe Terrell. Fact checking by Erica Akiko Howard. Mix and sound design by Bumi Hidaka and Peter Leonard. Music written by Peter Leonard, Bobby Lord, So Wylie, Bumi Hidaka, and Emma Munger. A huge thanks to all the people we spoke to for this episode including: Dr Jamie Harmann-Boyce, Prof Charlotta Pisinger, Prof Neal Benowitz, Dr Emily Stockings, Dr Mohammed Al-Hamdani, Prof Nancy Rigotti, Dr Elizabeth Stevens, Dr Matt Springer, Prof Paul Kenny, Dr Yasmeen Butt, Dr Sean Callahan, Dr Travis Henry, Professor Irfan Rahman, Christopher Harvel, Alex Sandorf, Dr James Pankow, Dr Konstantinos Farsalinos, Professor Lorraine Martin, Professor Moon-Shong Tang, Dr. Kevin Davidson and Myron Ronay. Extra thanks to Conor Duffy, the Zukerman Family and Joseph Lavelle Wilson.
[1] Michael Chaiton’s Manuscript: A longitudinal analysis of e-cigarette consumption in youth and the associated effect on respiratory health, by smoking status. “Currently there is only a small body of research surrounding e-cigarette consumption and its impact on respiratory health. Most of this research is cross-sectional, involves adult participants, and does not consider smoking status when assessing for respiratory effects.”
[2] “E-cigarettes were the most commonly used tobacco product overall (7.6%; 2.06 million), followed by cigarettes (1.5%)...” (US middle and high school students in 2021)
[3] 2015: “Among youth aged 15–19, 20% have tried vaping, compared to 11% who smoke tobacco, states the Canadian Tobacco, Alcohol and Drugs Survey.”
[4] “In 2021, youth e-cigarette use remains a serious public health concern, as approximately one in nine high school students (11.3%, 1.72 million) and one in 35 middle school students (2.8%, 320,000) had used e-cigarettes during the past 30 days.” Note: the source mentions changes in survey methods between 2020 and 2021 due to the pandemic.
[5] “In 2022, about 1 in 10 or more than 2.5 million U.S. middle and high school students currently used e-cigarettes (past 30-day).” Note: “Due to changes in methodology, including differences in survey administration and data collection procedures in recent years due to the COVID-19 pandemic, the ability to compare estimates from 2022 with those from prior NYTS waves is limited.”
[6] “Although the numbers of EVALI cases dropped dramatically during 2020, cases are still occurring.” [EVALI = e-cigarette or vaping use-associated lung injury]
[9] “Electronic cigarettes (ECIGs) are battery-operated devices that deliver nicotine to users via an inhalable aerosol mist.1−5 They have an electrical heating coil that physically contacts a liquid-saturated wick. When activated by the user, the coil heats and vaporizes the nicotine-containing liquid, which is composed primarily of propylene glycol (PG) and vegetable glycerin (VG). Available in hundreds of flavors,6 and particularly appealing to youth,7 this increasingly popular and diverse class of tobacco products8 has undergone continuous, major design developments ever since its introduction to the US market in 2007.”
[10] “Even though the term ‘vapor’ is normally used, vape devices do not produce water vapor. Vaping produces an aerosol mist. Unlike water vapor, the aerosol mist includes ultra-fine particles that are breathed into the lungs.”
[11] “Aerosol generated from an e-cigarette is commonly but inaccurately referred to as ‘vapour.’ Vapour refers to the gaseous state of a substance; in contrast, an aerosol is a suspension of fine particles of liquid, solid or both in a gas. Both the particulate and gas phases are mixtures of chemical substances in e-cigarette aerosols.”
[12] “...e-cigarettes have only been on the U.S. market for a relatively brief time—first imported in 2006, most have entered the market much more recently…” p2
[13] The US patent application describes "An electronic atomization cigarette that functions as substitutes for quitting smoking and cigarette substitutes..." (see also https://patents.google.com/patent/US7832410B2/en).
"The first device in the recent innovation in e-cigarettes was developed in 2003 by the Chinese pharmacist Hon Lik, a former deputy director of the Institute of Chinese Medicine in Liaoning Province. Lik’s patent application described a kind of electronic atomizing cigarette (Hon 2013). ... The product gained some attention among Chinese smokers early on as a potential cessation device or an alternative cigarette product. The e-cigarette was part of the U.S. market by the mid-2000s..."
[15] https://www.camh.ca/en/science-and-research/science-and-research-staff-directory/michaelchaiton
[16] This study has so far resulted in at least one published retrospective paper and an unpublished manuscript by Chaiton et al. looking at (largely) the same people longitudinally over time.
[17] “The outcome variable was the self-reported occurrence of adverse respiratory symptoms. Data on five respiratory symptoms were collected…”
[18] “The primary exposure variable was pack-equivalent years. This novel measure combines self-reported assessments of number of times the respondent takes a puff on a vape per day they vape (‘When you vape, how many puffs do you take?’), number of days vaped in the past month (‘On how many days, of the past 30 days, did you vape?’), and number of years since vaping started, calculated as current age subtracting reported age when the participant first vaped (‘How old were you when you first tried vaping?’). The pack-equivalent years measure is equivalent to the pack-years calculation for cigarettes.”
[19] Michael Chaiton’s Manuscript: A longitudinal analysis of e-cigarette consumption in youth and the associated effect on respiratory health, by smoking status. “Participants completed a baseline survey, and were followed up to complete additional surveys every 3 months for up to one year. It was found that with every unit increase of vaping consumption, there was a 15% increase in the risk of developing respiratory symptoms for non-smokers, a 6% increase for smokers, and a 9% increase overall.”
[20] Meta-Analysis: “Epidemiological studies, both cross-sectional and longitudinal, show a significant association of e-cigarette use with asthma and COPD, controlling for cigarette smoking and other covariates.”
[21] “Use of e-cigarettes is an independent risk factor for respiratory disease in addition to combustible tobacco smoking. Dual use, the most common use pattern, is riskier than using either product alone.”
[22] “Former e-cigarette use was associated with higher odds of developing any respiratory symptom (adjusted odds ratio [aOR], 1.20; 95% confidence interval [CI], 1.04–1.39) and wheezing in the chest (aOR, 1.41; 95% CI, 1.08–1.83) in multivariable adjusted models. Current e-cigarette use was associated with higher odds for any respiratory symptom (aOR, 1.32; 95% CI, 1.06–1.65) and wheezing in the chest (aOR, 1.51; 95% CI, 1.06–2.14). Associations persisted among participants who never smoked combustible cigarettes.” [aOR = adjusted odds ratio]
[23] “Compared with never e-cigarette users, past 30-day e-cigarette users reported increased odds of wheeze (OR 1.81; 95% CI 1.28, 2.56), bronchitic symptoms (OR 2.06; 95% CI 1.58, 2.69) and SOB (OR 1.78; 95% CI 1.23, 2.57), adjusting for study wave, age, sex, race, lifetime asthma diagnosis and parental education. Effect estimates were attenuated (wheeze (OR 1.41; 95% CI 0.99, 2.01), bronchitic symptoms (OR 1.55; 95% CI 1.18, 2.05), SOB (OR 1.48; 95% CI 1.01, 2.18)), after adjusting additionally for current cigarette use, cannabis use and secondhand exposure to e-cigarettes/cigarettes/cannabis.” [OR = odds ratio; SOB = shortness of breath]
[24] Michael Chaiton’s Manuscript: A longitudinal analysis of e-cigarette consumption in youth and the associated effect on respiratory health, by smoking status. “Participants were then followed up to complete an online survey every 3 months for up to one year.”
[25] Michael Chaiton’s Manuscript: A longitudinal analysis of e-cigarette consumption in youth and the associated effect on respiratory health, by smoking status. “…our analysis addresses the development of respiratory symptoms, which can serve as a precursor for such diseases, and poor respiratory health overall”
[26] ”Supplemental oxygen is a well-established therapy with clear evidence for benefit in patients with COPD and severe resting hypoxemia”
[27] “COPD is usually caused by smoking.3 Smoking accounts for as many as 8 out of 10 COPD-related deaths.6 However, as many as 1 out of 4 Americans with COPD never smoked cigarettes.5”
“Cigarette smoking is the most important risk factor for COPD [3]. In the U.S., approximately 80% of COPD deaths are linked to smoking, and 20% of smokers are expected to be diagnosed with COPD [4].”
[28] “A recent review of the literature found that on average studies showed a significant association of e-cigarette use with asthma and COPD, controlling for cigarette smoking and other covariates. For asthma (n=15 studies), the pooled adjusted odds ratio (AOR) was 1.39 (95% CI: 1.28–1.51); for COPD (n=9 studies) the AOR was 1.49 (95% CI: 1.36–1.65)21,22. Any use of vaping in short- or long-term was associated with asthma in youth aged 15–16 years23.”
[29] From baseline survey: See Table 2— 34.2% of the “Daily vaping, non-daily/never smoking” group have 0 symptoms
[30] A larger percentage of young adults (18-29) report that their first e-cig (71%) and usual (82%) were flavored compared to older adults (age 30+) (first 44%, usual 69%): “Young people used flavored e-cigarettes more than adults, especially at onset.”
[31] Survey (n= 1125) found that US adolescents 13-17 believed that fruit-flavoured e-cigarettes were less harmful to health than tobacco-flavoured e-cigarettes (p<0.05).
[32] Twitter analysis from 2012 and 2015 of vaping motivations “By 2015 the reasons for using ENDS cited on Twitter had shifted. Both quitting combustibles and use indoors significantly declined in mentions to 29% (95%CI 24–33) and 12% (95%CI 9–16), respectively. At the same time, social image increased to 37% (95%CI 32–43) and lack of odor increased to 5% (95%CI 2–5), the former leading all cited reasons in 2015. Our data suggest the reasons people vape are shifting away from cessation and toward social image…. Three of the 7 most cited reasons for vaping focused on evading policies, such as novel flavors (e.g., cherry) that have been banned in cigarettes” [ENDS = electronic nicotine delivery systems]
[33] US survey, ages 14–20: "Flavored product use predominated among past 30-day e-cigarette users. Ninety-two percent of users reported using flavored e-cigarettes in the past 30-days (Table 2). Past 30-day e-cigarette users most often endorsed fruit (61%), fruit-ice (47%) and menthol (45%) as flavors used in the past 30 days (Table 2). The majority (58%) endorsed ≥2 flavors; 32% endorsed ≥3 flavors. Combined, 76% endorsed a sweet flavor, and 70% endorsed a menthol flavor (Table 2). ... Flavored use was near universal regardless of device type or use frequency
[35] “the use of these vaping products can also introduce young adults to nicotine products and over 7000 flavors and other chemical constituents identified within these delivery systems.”
[36] “Among current e-cigarette users overall, 84.9% used flavored e-cigarettes; of these, the reported flavor types, in descending order of use, were fruit (69.1%); candy, desserts, or other sweets (38.3%); mint (29.4%); and menthol (26.6%).” (in US middle and high school students surveyed in 2022)
[37] “The move also includes a ban on all single use disposable vapes, restrictions on flavours, a shift to plain packaging, and a reduction in the concentration and volume of nicotine permitted in the devices.”
[39] “we investigated the effects of four common flavoring chemicals, cinnamaldehyde (cinnamon), ethyl vanillin (vanilla), benzaldehyde (almond or cherry), and isoamyl acetate (banana)” (NML version of full text)
[40] “Popcorn Lung Disease (Bronchiolitis obliterans) is an inflammatory disorder affecting the bronchioles, the smallest airways in the lungs. The scarring caused by swollen and irritated bronchioles creates airway obstructions.”
[41] Aug 2019, FDA is considering to add Diacetyl as a harmful and potentially harmful constituent (HPHCs) in tobacco products.
[42] “Diacetyl was detected above the laboratory limit of detection in 39 of the 51 flavors tested, ranging from below the limit of quantification to 239 μg/e-cigarette. 2,3-Pentanedione and acetoin were detected in 23 and 46 of the 51 flavors tested at concentrations up to 64 and 529 μg/e-cigarette, respectively.”
[43] (2018) “Currently, the most common flavoring chemicals in cigarettes and e-cigarettes in the market are menthol, diacetyl and 2,3-pentanedione (Table 1).”
[44] Recent 2018-19 study still found diacetyl and diacetyl alternatives (2,3-pentanedione and acetoin) in approximately half of samples tested (n=277);
[46] Obliterative Bronchiolitis pathogenesis “The use of diacetyl (and related chemicals, including 2,3-pentanedione) in the manufacture of food flavorings has been reported as a cause of obliterative bronchiolitis. The first case reports included workers from popcorn-processing plants in Missouri and Nebraska that were producing a butter flavoring”
[47] “In accordance with § 184.1(b)(1), the ingredient is used in food with no limitation other than current good manufacturing practice. The affirmation of this ingredient as generally recognized as safe (GRAS)...”
[48] “In 2000, a physician reported that eight former microwave-popcorn factory workers had developed a rare and disabling lung disease, bronchiolitis obliterans. Four of the eight workers were ill and put on lung transplant waiting lists.”
[49] “A 60 year old cigar smoking male was admitted with weakness, chills and cough. “ https://journal.chestnet.org/article/S0012-3692(16)35992-X/fulltext
[50] “the patient suffering from inhalation injury and suspected acute hypersensitivity pneumonitis used tobacco and an unspecified “sweet flavoring containing diacetyl” “ https://www.sciencedirect.com/science/article/pii/S2211335516300523
[51] “As noted by the Flavor Extracts Manufacturers Association (FEMA), flavors are safe for ingestion,
and not for inhalation. Many tobacco flavoring ingredients labeled ‘Generally Recognized as
Safe (GRAS)’ are intended for foods, but have not been evaluated for inhalation toxicity. The
composition of flavors differs as these are not FDA regulated”
[53] “Your liver’s biggest role is to filter your blood … Blood coming from your digestive system enters the liver through the hepatic portal vein carrying nutrients, medications, or toxins.”
[54] “These data suggest that some flavors (i.e., Banana Pudding Southern Style and Kola) tend to inhibit cell proliferation” "All flavored e-cig liquids (e-liquids) were purchased from The Vapor Girl (https://www.thevaporgirl.com/). The tested flavors were ... Banana Pudding (Southern Style) ... " See Tables 2 & 3 for the chemical constituents identified.
[56] “hBE cells were exposed to diluted cinnamon-flavored e-liquids and vaped aerosol… Both cinnamaldehyde-containing e-liquid and vaped aerosol rapidly yet transiently suppressed CBF, and exposure to cinnamaldehyde alone recapitulated this effect.” [hBE cells = human bronchial epithelial cells; CBF = ciliary beat frequency] …”Particles deposited on the epithelial surface during inspiration become trapped within airway mucus and motile airway cilia beat in coordinated metachronal waves to propel mucus particle aggregates toward the larynx (54).”
[58] Three cinnamaldehyde-containing e-liquids exhibited dose-dependent broadly immunosuppressive effects. Quantitative mass spectrometry was used to determine concentrations of cinnamaldehyde in each of the three e-liquids, and cells were subsequently challenged with a range of cinnamaldehyde concentrations. Cinnamaldehyde alone recapitulated the impaired function observed with e-liquid exposures, and cinnamaldehyde-induced suppression of macrophage phagocytosis was reversed by addition of the small-molecule reducing agent 1,4-dithiothreitol.
[59] We have previously shown that cinnamaldehyde impairs neutrophil phagocytosis.12 Here, we show that other aromatic aldehydes are also capable of impairing neutrophil phagocytosis. Ethyl vanillin, benzaldehyde, and benzaldehyde PG acetal significantly decreased neutrophil phagocytosis
[60] Technically, in petri dishes, plastic plates with multiple wells, or other labware. For example: "Neutrophils were seeded at a density of 1 × 105 in 100 μl volume/well of a cell culture-treated 96-well plate ... Neutrophils were seeded on 13-mm round glass coverslips (0.15 mm thick) ... Neutrophils isolated from venous blood were seeded at a density of 1 × 105 cells/well of a black clear-bottom 96-well plate ... Alveolar macrophages obtained from BAL fluid were seeded on black clear-bottom 96-well plates ... Alveolar macrophages were seeded on 13-mm round glass coverslips (0.15 mm thick) at 2 × 105 cells/well of a cell culture-treated 24-well plate. ... ETC." https://journals.physiology.org/doi/full/10.1152/ajplung.00452.2016
[61] “...e-cigarette liquids contain not only propylene glycol and glycerin but may also contain numerous contaminants, including polycyclic aromatic hydrocarbons, nitrosamines, endotoxins, diacetyl, and a wide variety of other organic and inorganic chemicals and flavoring compounds that may not be entirely inert.” (Supplementary Appendix, p10)
[62] “Major declared constituents in nicotine-based e-cigarettes include propylene glycol and glycerin,19 in addition to nicotine. Identified contaminants include polycyclic aromatic hydrocarbons, nitrosamines, volatile organic chemicals, and inorganic chemicals such as toxic metals.19,20 Endotoxins and flavoring compounds such as diacetyl and 2,3-pentanedione have also been detected. … In addition to nicotine, e-cigarette devices can be used to deliver a variety of other recreational drugs, including THC-based oils” (p913 in PDF version)
[63] https://link.springer.com/article/10.1057%2Fjphp.2010.41 labs have found (from table 1): propylene glycol (PG), glycerin, nicotine, tobacco-specific nitrosamines (TSNAs), diethylene glycol (DEG), 1,3-bis(3-phenoxyphenoxy)Benzene, 3-Isopropoxy-1,1,1,7,7,7-hexamethyl-3,5,5-tris(trimethylsiloxy)tetrasiloxane, α,3,4-tris[(trimethylsilyl)oxy]Benzeneacetic acid, acetaldehyde,1-methoxy-2-propanol,1-hydroxy-2-propanone,
acetic acid, 1-menthone, 2,3-butanediol, menthol, carvone, maple lactone, benzyl alcohol, 2-methyl-2-pentanoic acid, ethyl maltol, ethyl cinnamate, myosamine, benzoic acid, 2,3-bipyridine, cotinine, hexadecanoic acid, 1’1-oxybis-2-propanol
[64] “A high percentage of the liquid is composed of carrier solvents, such as glycerol and/or propylene glycol.”
[65] “Thermal degradation of e-cigarette solvent carriers glycerol and propylene glycol can also produce
carbonyls, such as formaldehyde, acetaldehyde, and acrolein (Tianrong, 2013; Hecht et al., 2015), that may cause pathophysiological changes once broken down into reactive oxidant species (Lerner et al., 2015a; Goel et al., 2015; Zhao et al., 2017; Lerner et al., 2015b), potentially contributing to cardiomyopathy (Henning et al., 2017).”
[66] “Exposure to PG mist may occur from smoke generators in discotheques, theatres, and aviation emergency training.”
[67] “Artificial fog is commonly employed in the entertainment industry and indoor household celebrations. The fog is generated from glycol-based solvents, which can also be found in e-cigarettes and personal care products. … Specifically, we targeted artificial fogs generated with common glycols, including propylene glycol (PG)...”
[68] “After exposure to PG mist for 1 minute tear film stability decreased, ocular and throat symptoms increased, forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) was slightly reduced, and self rated severity of dyspnoea was slightly increased.”
[69]Also inhibits lung cell division in petri dishes: “Exposure of SAECs to PG significantly inhibited proliferation (1%, PG, p = 0.021; 2–4% PG, p < 0.0001) and decreased cell viability (1–4% PG, p < 0.0001) in a concentration-dependent manner.” [SAECs= small airway epithelial cells; PG = propylene glycol]
[70] “We found preliminary evidence EC users had greater pulmonary inflammation than cigarette smokers and never smoke/vape controls, with a positive association between pulmonary and peripheral measures of inflammation.” [EC = electronic cigarette]
[73] “Nicotine is what keeps people using tobacco products. However, it’s the thousands of chemicals contained in tobacco and tobacco smoke that make tobacco use so deadly. Some of these chemicals, known to cause lung damage, are also found in some e-cigarette aerosols. This toxic mix of chemicals—not nicotine—cause the serious health effects among those who use tobacco products, including fatal lung diseases, like chronic obstructive pulmonary disease (COPD) and cancer.”
[74] “Approximately 50 million people in the United States alone are addicted to tobacco products (Creamer et al., 2019), resulting in tremendous public health, societal, and economic costs. Nicotine is the main addictive component of tobacco products”
[75]Elf bars- very popular disposable vape- can have up to 50mg/ml nicotine (5%) “Nicotine Strength: 0%/3%/5%”
[76] “One study estimated 68% transfer efficiency to the aerosol, measuring 28.8 mg nicotine per JUULpod. The other studies reported nicotine values ranging from 72 to 164 µg/puff. At 200 puffs, this is 14.4-32.8 mg of nicotine per pod with equivalence to 13-30 cigarettes.”
[77] “One JUULpod appears capable of delivering the nicotine equivalent to smoking about a pack of cigarettes, with variability….Minimising harshness and adaptive to user experience, JUUL’s design facilitates initiation to a high nicotine, and ultimately, highly addictive vaping product.”
[78] “Liquids differ from those of previous generations insofar as they contain high concentrations of nicotine (∼50–60 mg/mL) and an acid that protonates the nicotine and makes the aerosol less harsh [24]; the combination of high nicotine concentrations in an acidic aerosol may increase the potential for addiction in inexperienced users.”
[79] “Our study documents that JUUL’s success in the e-cigarette marketplace has spurred a variety of new pod-based products with exceptionally high nicotine. Despite the cleverness of its design features, a historian 20 years from now may conclude that JUUL’s most consequential impact was that it introduced markedly higher nicotine concentrations to the e-cigarette market. … JUUL is not intended as a means of weaning off of nicotine addiction, but rather has a business model based on ongoing sales of consumables (JUUL pods). In 2015, Ari Atkins, a JUUL engineer, commented: ‘We don’t think a lot about addiction here because we’re not trying to design a cessation product at all.’ ”
[80] “There is no consensus in the way nicotine strength is reported on labels of products or in studies. The nicotine strength on the label of some products is qualitative (e.g., zero, low, medium, high, super high) or quantitative on others.”
[81] 2019 Paper: “We purchased ten “nicotine-free” e-liquids of a variety of brands and flavours, online and over the counter from Australian suppliers. None disclosed ingredient information beyond vague reporting of the excipient mix and the absence of nicotine. … Nicotine was detected in six e-liquids; the levels in three (1.3, 1.4, 2.9 mg/mL) were comparable with those of commonly available low dose nicotine e-liquids.”
[82] “The results from the testing found that (1) the nicotine content labeling was not accurate with some manufacturers … Some products were found to contain high concentrations of nicotine when labeled not to contain nicotine.”
[83] “These data demonstrate that DIY flavouring products, which are marketed for the purpose of flavour enhancement, may contain substantial amounts of nicotine. … These products, which are presented to the consumer as ‘nicotine free’ … could lead to unwanted addiction, poisoning, or even death.”
[84] 1986: “In our study the prevalence of smoking was higher than expected among those with schizophrenia, mania, depression, anxiety, and personality disorders.”
[85] 1990 “The cross-sectional analysis of the first National Health and Nutrition Examination Survey showed that the prevalence of current smokers increased as the Center for Epidemiologic Studies Depression Scale score increased, whereas the quit ratio (former smokers/ever smokers) decreased as the Center for Epidemiologic Studies Depression Scale score increased.”
[86] 1990 “Depressed subjects are more likely to have ever smoked, and they are less likely to have been successful in their efforts to stop smoking (Table 1)....Once the adverse impact of a history of depression on smoking cessation became apparent, it seemed reasonable to ask whether these smokers failed to quit because they developed depressive symptoms during nicotine withdrawal.”
[87] 1998 study: “Results of our study confirm a relationship between depression, negative affect and cigarette consumption and, especially, in the subjects with a consumption of 31 or more cigarettes daily…The first report on the association between smoking and psychiatric status was published in 1986 (Hughes et al., 1986). It reported a significantly greater smoking prevalence among subjects with major depression, anxiety and schizophrenia.”
[88] 2003: “Table 1 shows that, at all ages, those with major depression had significantly (P<0.001) elevated rates of both daily cigarette intake and nicotine dependence….[E]ven after extensive control for fixed and confounding factors there were still small but detectable tendencies for major depression to be associated with increased risks of cigarette smoking. The adjusted risk ratios show that major depression was associated with a 19% increase in average daily cigarette intake and a 1.75 times increase in the odds of nicotine dependence.”
[89] 2022 Review: “Five of the seven studies included depression as a primary outcome. Lechner et al. (2017), discovered that continued use of electronic cigarettes (EC) with or without concurrent use of CC worsened depressive symptoms, resulting in a deterioration of the individual’s mental health.9 Lechner and colleagues showed a bidirectional relationship between EC use and depression and noticed that adolescents who were depressed were more likely to initiate EC use and dual-use than non-users. ….These findings were reinforced by many other studies (i.e., Lee & Lee, 2019; Chadi et al., 2019 and Jee, 2016), all of whom reported finding higher levels of depression in EC users.10–12” [CC = combustible cigarettes]
[90] “Overall, 3.7% and 11.2% of the participants were current and former e-cigarette users, respectively. A significantly higher proportion of current e-cigarette users reported having depression (32.4%) than former users (27.3%) and non-users (16.0%).” (US adults)
[91] “Overall, in the multivariable modeling, e-cigarette use was consistently associated with poor mental health among non-smokers and women, a finding that persisted after adjustment for additional covariates.” (in Canadians)
[92] 2017 Paper—”A bi-directional association of depressive symptoms with e-cigarette use onset across mid adolescence was observed. Further research on the causal nature, etiological underpinnings, and intervention implications of mental health and tobacco product use comorbidity is warranted.”
[93] 2021 Paper— “Greater depressive symptoms at age 14 years old were associated with a faster rate of e-cigarette escalation. However, e-cigarette use was not related to the development of depression symptoms over time.”
[94] “EC past-30-day use was, however, associated with suicide ideation (aOR= 2.49, 95% CI =1.82-3.42),
suicide planning (aOR= 4.63, 95% CI=3.22-6.67), and suicide attempts (aOR=6.17, 95% CI =6.17, 95% CI=4.13-9.24).” [EC = e-cigarette; aOR = adjusted odds ratio]
[95] “Supporting evidence for this relationship comes from longitudinal investigations in which both depression symptoms (McKenzie, Olsson, Jorm, Romaniuk, & Patton, 2010) as well as a diagnosis of major depression (Breslau et al., 1993, Breslau et al., 1998, Dierker et al., 2001) have been shown to be associated with increased risk of future smoking, the progression to nicotine dependence among adolescents (Fergusson, Lynskey, & Horwood, 1996) and adults (Breslau, Scott, & Kessler, 2004) and a decreased likelihood of successful smoking cessation (McClave et al., 2009).”
[96] “The prevalence of depression among those with a high nicotine dependence level, as assessed by the Fagerstrom Tolerance Questionnaire, was about twice that of people with a low nicotine dependence level. … The cross-sectional nature of the data represents another limitation of this analysis, as directional causation cannot be addressed. The extent to which smoking may influence the development or persistence of depression, as opposed to an effect of depression onsmoking initiation or persistence, cannot be fully determined…”
[97] 1-year longitudinal study: “For the nondepressed, multivariate modeling revealed that current cigarette smoking was the strongest predictor of developing high depressive symptoms in all models (final model odds ratio [OR]: 3.90; 95% confidence interval [CI]: 1.85,8.20). … In contrast to common dictum, depression does not seem to be an antecedent to heavy cigarette use among teens. However, current cigarette use is a powerful determinant of developing high depressive symptoms.”
[98] 2020 Mendelian Randomisation study: “There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001).”
[99] “Women smoking more than 10 g of tobacco per day were at significantly increased risk of
depression compared to women who did not smoke. The adjusted risk of depression among women
smoking 11-20 g per day was 1.74 (CI:1.33-2.27) and 2.17 (CI:1.45-3.26) among women smoking more
than 20 g per day. For men, there was an increased risk of depression for those smoking more than 20 g
[100] “Five studies involving 1193 people with a history of depression (307 quitters) found there was no increased risk of depression following smoking cessation.21,31–34 Two of these five studies found an improvement in depressive symptoms among the abstainers. Kahler et al. found significant reductions in depressive symptoms among continuous abstainers, at 1 and 12 months after quitting.21 Blalock et al. found an association between prolonged abstinence from smoking and an increase in positive affect, and a decrease in depressive symptoms.33”
[101] “In the current study, depressed smokers who were able to abstain were more likely to experience positive changes in depressive symptoms and PA than were those who were unable to abstain. These findings could be viewed as supportive of the hypothesis that chronic exposure to tobacco smoke induces depression. These findings could also be viewed as evidence that nicotine is ineffective in alleviating depressive symptoms, which is inconsistent with the self-medication hypothesis. However, it is important to note that the direction of the affect–abstinence effect cannot be discerned within the current study because it was not designed to evaluate the nature or direction of the relationship of these variables.”
[102] “The quit ratio increased among individuals with (28.61% to 39.75%; AOR=1.036, 95% CI=1.021, 1.052) and without depression (47.65% to 53.09%; AOR=1.013, 95% CI=1.009, 1.017), yet quit ratios were consistently lower for those with depression than those without depression.” *These results were for adults: “respondents aged ≥26 years were included in analyses of quit ratio (n=131,412)”
[103] “Although the co-morbidities between cigarette smoking and depression have been well documented, the mechanisms leading to these associations remain controversial. There are two general explanations of the association: confounding and selection; and causation.”
[104] “Nicotine use may increase vulnerability to depression as nicotine influences several neurochemical systems, such as acetylcholine and catecholamine systems (Pomerleau and Pomerleau, 1984), which may play an etiologic role in depression (Carmody et al., 2007)”
[105] “In previous studies nicotine has been administered through experimenter-delivered injections (Kasten et al., 2016) or subcutaneous minipumps (LeSage et al., 2002). These models provide the benefit of standardized serum nicotine levels; however, these have limitations related to surgery and/or injection induced stress. A voluntary route of nicotine delivery is oral consumption with bottle choice which showed nicotine-induced hypothermic and locomotor effects (Kasten et al., 2016; O’Rourke et al., 2016; DeBaker et al., 2020). However, this model of nicotine exposure does not replicate human consumption of nicotine and raises questions regarding taste preference when paired with other substances like sucrose. Nicotine administered via inhalation of vapor has become an emerging route of human consumption thus, preclinical studies should aim to reflect this route of administration.”
[107] “...self-administration of nicotine vapor has recently been demonstrated in rodents (Smith et al., 2020; Cooper et al., 2021; Lallai et al., 2021) and it has been shown that self-administration of nicotine vapor can be enhanced with the addition of e-liquid flavors such as green apple and menthol”
[108] Relevant studies from Melissa’s lab: Zhu et al 2021 looks at males only, Echeveste Sanchez et al. 2023— both males and females (note: results differ by sex)
[109] “Immediately following acute electronic vapor exposure (PG/VG N = 6, Nic N = 6) or the last session of repeated electronic vapor exposure (PG/VG N = 6, Nic N = 6), mice were rapidly decapitated, and brains were extracted and placed into an ice-cold sucrose solution containing the following: 206.0 mm sucrose, 2.5 mm KCl, 0.5 mm CaCl2, 7.0 mm MgCl2, 1.2 mm NaH2PO4, 26 mm NaHCO3, 5.0 mm glucose, and 5 mm HEPES. Coronal slices (300 μm thick) containing the CeA were prepared”
[110] “The central nucleus of amygdala (CeA) mediates positively-valenced reward motivation as well as negatively-valenced fear. … Indeed, amygdala neurons are activated by both positively and negatively valenced stimuli [8,9]. It has been suggested that amygdala integrates affective significance with internal physiological state to coordinate actions [10].”
[111] “Cold Spring Harbor Laboratory neuroscientist Bo Li has brought us several important steps closer. His lab recently made a series of discoveries that show how neurons called somatostatin-expressing (Sst+) central amygdala (CeA) neurons help us learn about threats and rewards.” “Scientists have discovered that somatostatin-expressing neurons in the amygdala help distinguish between good and bad stimuli, responding differently to rewards versus punishments and even different types of rewards. Inhibiting these neurons in mice resulted in an inability to learn to associate sounds with rewards or punishments”
[112] “In this context, the CeA has been implicated in numerous adaptive behaviors (feeding, fear learning, stress; Ciocchi et al., 2010; Gilpin et al., 2015; Douglass et al., 2017) and maladaptive conditions (anxiety, depression, chronic stress, addiction; Koob et al., 1998; Kenny et al., 2009; Gilpin et al., 2015; Bolton et al., 2018).” [CeA = central amygdala]
[113] “In contrast to what was observed with acute exposure, following 5 d of repeated electronic nicotine vapor sessions, there was no increase in CeA activity observed by either electrophysiological or immunohistochemical evaluation” (in male mice only)
[114] “The mesolimbic system, also known as the reward system, is composed of brain structures that are responsible for mediating the physiological and cognitive processing of reward. … Dopamine plays a critical role in mediating the reward value of food, drink, sex, social interaction, and substance abuse”
[115] “Our data support the hypothesis that smoking and nicotine exposure have an impact on reward processing in DArgic pathway terminal regions that mediate motivational processing. They also extend previous observations regarding smoking-related reductions in anticipatory activity by delineating state- and trait-specific effects of nicotine/smoking on dissociable reward processes.” [DArgic = dopaminergic]
[116] “The mesocorticolimbic dopamine system (Figure 1), comprising cell bodies in the ventral tegmental area (VTA) and their projections to the nucleus accumbens (NAc) as well as other forebrain sites including the dorsal striatum and the prefrontal cortex (PFC), is regarded as the major substrate of reward and reinforcement for both natural rewards and addictive drugs, such as nicotine”
[117] “Once nicotine enters the pulmonary venous circulation, it then enters the arterial circulation and rapidly moves across the blood–brain barrier into the brain (Benowitz, 2009). Nicotine then diffuses readily in brain tissue and (S)-nicotine, the predominant form, binds stereoselectively to nicotine cholinergic receptors (nAChRs)...Nicotine-induced stimulation of central nervous system nAChRs results in the release of multiple neurotransmitters in the brain, dopamine being dominant”
[118] “In the case of tobacco products, the principal addictive component is nicotine, which interacts with specific membrane receptors in the nervous system known as neuronal nicotinic acetylcholine receptors (nAChRs).”
[119] “Once nicotine has entered the body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within 10–20 sec after inhalation (Le Houezec 2003). Once in the brain, it binds to its target, the nicotinic acetylcholine receptors (nAChR)...”
[120] “A common feature of many addictive drugs, including nicotine, is that they increase dopamine (DA)
[121] “Nicotine levels in chronic smokers measured during the day, however, revealed blood nicotine concentrations ranging from 10 to 50 ng/ml (60 to 300 nM) (Benowitz et al., 1989); thus, the sustained elevated nicotine levels experienced by chronic smokers throughout the day could result in cycles of both nAChR activation and desensitization. The desensitization, in particular, may be related to receptor occupancy given the higher affinity of desensitized nAChRs. Furthermore, recent reports suggest that nAChR occupancy is nearly complete after 1 cigarette (Brody et al., 2006).” [nAChR = nicotinic acetylcholine receptors]
[122] “Nicotine has an average terminal half-life of two hours. With regular dosing blood nicotine levels rise over 6-8 hours, then plateau throughout the rest of the day during smoking. The pattern of human exposure is a combination of intermittent peaks and troughs throughout the day, with gradually declining nicotine exposure overnight. Typically average blood nicotine concentrations are 10-40ng/ml. Levels in the brain or heart are 2-3 fold higher.”
[123] “As nicotine enters the brain more gradually and is cleared more slowly than endogenous ACh, nicotine has the ability to induce more sustained desensitization of nAChRs (DeBry and Tiffany 2008). In this regard, exogenous nicotine can potentially exert a more profound inhibition of nAChRs than endogenous acetylcholine, leading to a potential decrease in release of various neurotransmitters.”
[124] “Cigarette smoking in amounts that are typical for daily smokers maintains near-complete saturation — and thus desensitization — of the α4 β2* nicotinic cholinergic receptors.27”
One Ad-libitum study, See Figure 2: “participants vaped intermittently throughout the 90-minute session. This led to a gradual rise in plasma nicotine levels which peaked at the end of the session.”
[125] “The sustained elevation of extracellular dopamine for 60–120 min after a single injection of nicotine is characteristic of the response [40,48], and subsequent injections of drug in the 90 min period following a nicotine injection have little additional effect on dopamine overflow”
[126] “While chronic nicotine exposure leads to receptor desensitization, it also leads to compensatory changes such as up-regulation of nicotine binding sites. Chronic nicotine exposure has been shown to lead to robust nAChR up-regulation in both human smokers and in animal models. For instance, in post-mortem brains, increased high affinity nAChR binding has been observed in several regions including the cortex and hippocampus (Benwell et al., 1988; Perry et al., 1999).”
[127] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554201/
“Chronic nicotine exposure results in numerous neuroadaptations, including the upregulation of particular nAChR subtypes associated with long-term desensitization of the receptors.” “In addition to altering nAChR expression levels in specific brain regions, repeated nicotine exposure can also produce a variety of additional neuroadaptations throughout the brain”
[128] “Repeated or chronic exposure to nicotine induces a decrease or loss of the N-like response and increases the number of nAChRs, rather than reducing their number [77]. This response may result from the ability of nicotine to desensitize or inactivate nAChRs [62], [93]. Indeed, prolonged incubation with low levels of nicotine, such as that which occurs when smoking, results in little receptor activation; however, it effectively blocks the nAChRs by stabilizing the desensitized states of the receptor”
[129] “With agonist binding, receptors rapidly activate by opening the ion channel through the receptor. Activation is a metastable event. If the receptor remains bound by agonist, activation is quickly followed by a second conformational change into a nonfunctional state termed desensitization in which the channel is closed [74]. Normally, receptors rapidly recover from the desensitized state and enter the resting state when nicotine is removed. Several lines of evidence indicate that chronic exposure to nicotine causes some of the nicotinic receptors in the brain to undergo long-lasting state changes. These conformational changes are distinguished from activation and desensitization by much slower kinetics (on the order of hours to days).”
[130] “Our results indicate that the concentrations of nicotine obtained by smoking can acutely excite dopaminergic VTA neurons to fire action potentials. This activity would initiate dopamine release in the NAcc and, in that way, is likely to be an important cellular mechanism for nicotine’s rewarding effects3–7,10. A smoker, however, maintains a rather steady low-level background of nicotine throughout the day5,16, and our results indicate that longer exposures to nicotine can cause severe desensitization of VTA nAChRs.” ….”The effects suggest a cellular basis for reports that the first cigarette of the day is the most pleasurable, whereas the effect of subsequent cigarettes may depend on the interplay between activation and desensitization of multiple nicotinic receptors”
[131] “While somewhat modest in size, the literature on chronic tolerance to nicotine in humans is reasonably consistent in showing clear evidence of tolerance to subjective mood effects but little or no tolerance to cardiovascular, performance or other nicotine effects, within the limitations inherent in most human research on tolerance.”
[132] “Our results indicate that elevations in ICSS reward thresholds observed in rats during nicotine abstinence may be a useful model of the affective aspects of nicotine withdrawal in humans. These results also demonstrate a profound perturbation within brain reward circuitries produced by chronic nicotine administration that may contribute to nicotine addiction.” [ICSS = intracranial self-stimulation]
[133] “Dysfunctional reward processing leading to the undervaluation of non-drug rewards is hypothesized to play a crucial role in nicotine dependence.”
[134] “desensitization of nAChRs by low concentrations of nicotine lead to reduced release of GABA and dopamine in mice brains (Grady et al. 2012). These effects may underpin observations in human studies of depression, where nicotine and other cigarette components altering neurotransmitter system may partially explain development of depressed states (Dome et al. 2010).”
[135] “Since the ordinary role of this brain system is putatively to attribute incentive properties to rewarding stimuli, any dampening of activity in regular drug users is likely to be associated with decreased sensitivity to incentives of everyday life. This would be unmasked during periods of drug abstinence or during a quit attempt since the individual would no longer benefit from the short-term DA-enhancing effects of drug taking.” [DA = dopamine or dopaminergic?]
[136]“It is hypothesized that a relative deficiency in dopamine release following long-standing nicotine exposure accounts for many of the mood disorders and the anhedonia, as well as the tobacco craving, that may persist in smokers for a long time after they have quit.”
[137] “Anhedonia, a core feature of depression, is a multi-faceted symptom that includes deficits in the experience of pleasure, reduced approach-related motivated behavior, and/or impaired learning about rewards in the environment”
[138] “Cumulative exposure to vaping based on vaping frequency and length of time vaping was associated with increased numbers of respiratory symptoms that can, with sufficient dose, approach the short-term respiratory harms associated with smoking cigarettes.” “This population of youth and young adults reflects a lighter smoking sample than would be found among all adults. Exclusive daily smokers reported smoking an average of 9.8 cigarettes per day, while dual users reported smoking an average of 5.7 cigarettes per day, which is notably lower than previous research that showed an average daily cigarette consumption among Canadian daily smokers of 13.7 in 201720. Despite this level of smoking, elevated respiratory symptoms were higher in smokers than non-smokers indicating the dangerousness of cigarettes.”
[139] “Cigarette smoking causes 3 in 10 of all cancer deaths.”
“About one-third of cancer deaths in this country can be attributed to cigarette smoking and exposure to secondhand smoke.”
[140] “Tobacco is an important public health issue and the single most preventable cause of illness and death in the world. The latest research suggests that smoking-related mortality has risen to 7.2 million lives annually…”
[141] “Tobacco smoking is the world's leading cause of avoidable premature mortality, reflecting the potent toxicity of tobacco smoke inhaled by smokers for decades.”
[142] “Cigarette smoking is responsible for more than 480,000 deaths per year in the United States, including more than 41,000 deaths resulting from secondhand smoke exposure. This is about one in five deaths annually, or 1,300 deaths every day.” “Smoking is the leading cause of preventable death.”