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Alcohol Toxicity, Vaping vs. Smoking, Tobacco, Nicotine, Marijuana, Terpenes, THC, Toxicology

Full auto-generated transcript below. Beware of typos & mistranslations!

Nick Jikomes

What kind of scientist you are and what that means.

Echo Rufer 6:01

Yeah, so I am a formally educated toxicologist. So I have a degree in pharmacology and toxicology, bachelor's, and then I have a PhD in Molecular and Environmental Toxicology. And that has really taken me some interesting places it is I have not taken the career path of the typical toxicologist. So

I currently work as the Director of Health Sciences at PAX labs. Basically, my job here at Pax is to understand the effects of our cannabis products, and how that can affect

So what kind of scientist am I? I am one I would say that really likes the puzzle. So I like to figure out what's happening. And why to help us understand knowing that everything with cannabis especially is a puzzle, and will continue to be a puzzle because it is just a very complex

science. So that makes it exciting for me.

Nick Jikomes 7:22

And so what toxicology is it? Is it just what it sounds like? Basically, the scientific study of toxins and how they affect the body?

Echo Rufer 7:30

Yeah, so I would say it started out back in, you know, like, the major textbook that everybody uses for toxicology is called The Science of poisons. I would say that's what it was historically, when it started and more, more within the last few decades has become more of the science of safety, and really understanding how can we make things safer. And because like we can, we can make things really toxic. And you know, you can see some interesting stuff from that. But that's just really interesting. And so it's turned a lot into understanding risk. And risk is really I think what people want to know about and risk is the likelihood of seeing some sort of negative effect. And that's what a lot of toxicologists spend their time on. And there's kind of two components that make up the risk of a substance or a product or, you know, whatever it is that you're you're looking at, and toxicologists will spend a lot of time on those two aspects, one of them is oftentimes called hazard. What that essentially means is what is the inherent toxicity of a substance, so you might have alcohol that, you know, can, in some cases, it can cause cancer, it can cause what would be called in, you know, by toxicologist neurotoxicity. Others might call it being drunk, as well as you know, liver cirrhosis, all these other sorts of things that can happen. And that's very interesting. However, that is not risk that is hazard. And the other piece that is extremely important is exposure. So how much you're actually exposed to is hugely important, no matter what it is that you're looking at, because we know many people drink alcohol or consume cannabis. And we don't see those effects that are often characterized in that hazard, sort of Toxicological Research.

Nick Jikomes 9:31

I see. And I know I know, we're not talking really about alcohol today. I like when you get drunk and you get a hangover. What is that?

Echo Rufer 9:40

It's funny, you talk about alcohol because my PhD thesis project was actually on fetal alcohol syndrome. So it's thought to be very much associated with dehydration. And, you know, when you're drinking alcohol, you're oftentimes not drinking water and it tends to dehydrate There's probably some other effects, I know that there's some certain genetic abnormalities that not abnormalities, differences, that might lead to different metabolism of alcohol that can lead to an abundance of a toxic intermediate called acid aldehyde. And that can lead to it feeling unpleasant. And this is oftentimes seen as a flushing syndrome. Not quite a hangover, but others also have might have some over acid aldehyde leftover if they drink too much, and it doesn't make you feel very good.

Nick Jikomes 10:34

And that's just a natural, like metabolic byproduct of consuming ethanol.

Echo Rufer 10:39

Yeah, so when you consume ethanol, let me think about it. There's an alcohol dehydrogenase. That metabolizes it, no SIP to one metabolizes it to some extent, and then there's an it's an alcohol and then you end up with an aldehyde dehydrogenase that changes it to water. And if you don't have enough of that final part of the metabolic pathway, you'll end up with that intermediate product, which is acid aldehyde, that everybody metabolizes it to it's just a different concentrations, depending on how much you drink and your metabolic capacity.

Nick Jikomes 11:16

I see. So like, depending on how much of that enzyme you have. And just depending on how much you drink is going to dictate how much the sort of leftover that turns into the bad, nasty aldehyde compound.

Echo Rufer 11:28

Yeah. And that's why like you can, there have been numerous studies to show that there is a difference between a binge drink which is over five drinks in a sitting versus five drinks over the week, you'll end up overloading when you do the binge drink, you'll end up overloading that metabolic capacity produce additional byproducts that you won't produce when you just drink a glass of wine every day, or some other sort of alcoholic beverage. And I'm talking to standard glass of wine, not like some of these college town drink specials that like, you know, a five a bottle or something like that is not is not a standard drink that counts as five drinks.

Nick Jikomes 12:10

And so, I mean, actually, maybe this is like related to, I guess, a foundational question here, which is like when you think about like, what is a toxin? Or what is a poison? You know, how much do we have to think about dose here? Because basically, what you decide with alcohol is right at a high enough dose, it's going to be quite toxic, potentially. And at a low enough dose, it might be not toxic at all, or very lightly toxic. And so one compound can can be toxic or non toxic, depending on how much you consume. Is that like a general principle?

Echo Rufer 12:43

Oh, yeah, that is absolutely there is a gentleman from the 16th century often called the godfather of toxicology Paracelsus, who has a, you know, a famous quote that is loosely stated in more of today's language, it's the dose that makes the poison. And so in, it's entirely related to dose and you know, coming back to cannabis. And cannabis is really interesting, because the dose of many cannabinoids tends to be biphasic, meaning at a lower dose, it might have one effect. And if you get it at a higher dose, it might be entirely the opposite. And so it is doses is key. Absolutely key. Okay, so

Nick Jikomes 13:33

I mean, not only can dose be a factor in terms of like, you know, as you increase the dose of something, it can become more and more toxic or create more and more of a toxic byproduct. But actually, a single drug can almost completely shift the physiological effects it will have at a relatively high versus relatively low dose.

Echo Rufer 13:51

Yeah, absolutely. Absolutely.

Nick Jikomes 13:54

And, you know, we're gonna talk a lot about vaping today, because that's what you focus on. Now. It's also I think, just an important topic, given how popular vaping is, of different kinds. So I want to talk about vaporization and combustion, you know, vaping versus smoking, generally speaking, independent of you know, whether we're talking about nicotine or cannabis or whatever. So what exactly is vaporization? And how is it different from smoking, where combustion is taking place, just in terms of the physical differences?

Echo Rufer 14:21

Yeah, so combustion is typically there's not a nice defined temperature where you can say when you hit this temperature at, you know, 927 degrees it now you're into combustion, it really is a continuum of a process. And so combustion occurs at much higher temperatures. So that's, you know, smoking, whatever it is that you're smoking, and at those high temperatures, it will break a host of substances down into other sorts of harmful byproducts. And, of course, all of them are being I would say volatilized and aerosolized so a, you know either a smoke or a vapor product actually produces some gas, and some liquid particles that are essentially floating around in that gas. And that gas that's produced is not just air, you know, a lot of your stuff sits in the gas phase, as well as the particulate phase vaporization uses a much lower temperature to aerosolized the, whatever it is that you're vaping. And so you're less likely to produce those harmful byproducts, but you're still are ending up with a particulate phase and a gas phase. And that's, that becomes that temperature becomes key. And that's why temperature is so important. We actually, and this is, is, you know, from the vape world, it can be significantly different depending on the device that you're using. So we actually published a paper, I think, late 2021. That used a thermal camera, that's called thermography. And we measured cannabis vape cartridges during a puff and said, Okay, what is the temperature of that coil of our devices, as well as some other competitors that that we just randomly pick them off of the shelf, we chose one that was a little more expensive, that had a couple of voltage settings, and we choose chose one that was kind of like something that might be a freebie, when you buy a product at a dispensary, they might give it to you for free, as well as some of the packs devices. And what we found was, you know, not surprising to us, because this is how the products were designed. And that the are the packs products were between 204 120 degrees Celsius, plus or minus 10% of what is set on the device. The others, I think one reached depending on the setting, one I think had a low dose of like 420 degrees Celsius, and another one reached up to 600 degrees Celsius. So that that combustion sort of process or pyrolysis process that happens as you get hotter and hotter, can start to happen in the 400 500 600. C, and then of course, works that way up. Some combustion, like the cherry have a cigarette, I think has been measured to be around 1000 degrees Celsius. So

Nick Jikomes 17:29

I see. So in a relatively low heat setting, you're causing molecules in the solid material to enter the gas phase, so they can be inhaled. But as you keep increasing the temperature, eventually you don't just vaporize things, combustion happens, there's fire, and basically you start melting, and chemically transforming that stuff. And whatever it is, if you're melting it, you're likely to produce some number of toxic byproducts that came from that original material is that basically how it works,

Echo Rufer 18:03

I wouldn't use the word melt, though, because melt is not a chemical change, right? That's going from a solid to a liquid. It is it is an actual breakdown of the product. But you know, every every substance has a vapor pressure. So at a temperature and pressure that it will become more the gas phase. And then in some of these devices, it's actually bringing along some of the liquid phase as well.

Nick Jikomes 18:30

So so you can you can make things turn into the gas phase by applying heat in if you keep applying heat at some temperature, depending on the molecule, the actual chemical compound will transform into something else, that oftentimes that something else is not a good thing.

Echo Rufer 18:45

Right. Right. And that's in the the Well, I would say the nicotine tobacco space, they've actually identified a host of substances called HP HCS are harmful and potentially harmful constituents that are harmful, obviously, for different reasons, whether it's from a carcinogenicity standpoint, respiratory toxicity standpoint that have been identified, that are essentially common degradations of plant material. So some of those are actually formed in cannabis cigarettes or joints the same way they are in tobacco cigarettes, and those are produced to some extent in some vape products. But, you know, if the temperature is controlled is much, much lower than what is observed in smoking.

Nick Jikomes 19:41

So it's a fair statement, a generally true statement. You know, if you're inhaling something, whatever it is, the lower the temperature, the better it's probably going to be or the the less toxic compounds will be produced.

Echo Rufer 19:55

You're going to be inhaling what it is that you see the lower the temperature it is and the less likely of this, that you'll produce this other stuff now, can you, you know, vape, a cannabinoid at 100 degrees Celsius. No, they won't aerosolized at that, at that temperature. So you do have a minimum that you can and we know that cannabinoids vaporize at a higher temperature than E cigarettes or nicotine. And so, you know, we do I do hear about a lot of consumers that are very concerned about some of the temperatures of these devices. They're saying, Well, my, you know, my E cigarettes at this temperature, but you know, you're just burning the material. And it's like, well, actually, it's not it's just cannabinoids are different cannabinoids are not nicotine, they work differently. So if you want to vaporize them, you kind of are stuck a little bit higher temperature.

Nick Jikomes 20:53

And I think, you know, on the question of nicotine and smoking tobacco, in particular, so if you imagine someone smoking cigarettes, we've all seen people doing that. At this point. I think everybody knows, right? There's clear health risks associated with that. We know that, you know, nicotine is addictive. We know that there's an increased cancer risk. And there's cardiovascular issues associated with smoking tobacco products. But in general, in terms of the negative health risks associated with smoking tobacco, specifically, how much of that is the nicotine itself versus some of these toxic byproducts that come from combustion? Or like other things that the companies add to the cigarettes? Like what's causing what in terms of like cancer risk and all of that stuff?

Echo Rufer 21:35

Yeah, it's really an interesting question. And tobacco cigarettes are have been named by the CDC as the number one cause of preventable death. And, you know, it causes a host of different types of toxicity, right. So there's carcinogenicity, there's respiratory toxicity in your CBD, or your COPD as your cardiovascular diseases. And what we've, I think, observed from other forms of nicotine intake, is that much of that risk appears to be driven by these byproducts, there's some work that has been done on the, those HPH sees those harmful degradation products. I'm trying to identify like the, the tobacco industry has went through and identified every components of that they can identify in the smoke of a cigarette, tested each of those in different models of carcinogenicity as an example, and found that there are four or five of those HPH C's that appear to be responsible for the majority of at least the carcinogenicity. So like 80%, is driven by these four or five substances what's what's HPAC? Again, hphc, the harmful and potentially harmful constituents?

Nick Jikomes 23:00

Okay, what do you do know what those are?

Echo Rufer 23:03

Yeah, there's, there's a list of like, I think it's 93 of them that the FDA has defined. So they're things like formaldehyde, acid, aldehyde, lead, there's tobacco specific nitrosamines, there's poly aromatic hydrocarbons. There's a lot of substances on that list that are, at this point, pretty well defined, but even go within a subset of that list. Those seem to be responsible for a lot of the toxicity. And it's not to say the other things are, are risk free. You know, I'm a toxicologist. We talked about dose, I will never say anything is risk free. There are examples of someone overdosing on water, pure water, not contaminated water, just pure water. So yeah, it appears to be a lot of those byproducts associated with combustion.

Nick Jikomes 23:55

Okay, so in tobacco smoke, you get all these byproducts, there's dozens and dozens of them that have been identified as being carcinogenic or toxic in some way. But there's really just a handful that drive most of the problem there. So there's a lot of nasty stuff in there. But there's like a handful of things that drive most of the problems that are associated with smoking tobacco.

Echo Rufer 24:15

Yeah, based on their concentration and the hazard of those specific ingredients. That's what seems to be the case. And that's why, you know, the vaporization products, and, you know, talking about significant reductions, and a lot of these ingredients is because they are so key. It's not to say these other pieces are, like I said, totally risk free. It's just that, you know, hey, we've got the number one cause of preventable death if we can come 98% of the way from that. Like, you know, it makes sense.

Nick Jikomes 24:50

And what about nicotine itself? I mean, nicotine is a psycho stimulant that has, you know, kind of an alerting effect. It is we know that it's highly addictive. Have is it I assume at some dose eventually, you know, it's toxic just like anything else at a high enough dose. But at a dose that a tobacco consumer is typically your average tobacco consumer is going to be ingesting is nicotine itself toxic or carcinogenic or anything.

Echo Rufer 25:14

It's not carcinogenic. And I will say I've not spent as much time on the nicotine front as I have in the cannabis front. But nicotine from my read is not the one causing the carcinogenicity is not the one causing a lot of the respiratory toxicity. Now, is it maybe involved in some of the cardiovascular stuff? That's much harder to test for? I mean, I would imagine there's some possibility, but there is what's interesting about nicotine itself is it has what's called a very, like a low therapeutic or a narrow therapeutic window. So in order to feel the effects versus where like, if you swallow a load of nicotine, you can overdose relatively easily and die on, you know, consuming a not as large amount of nicotine as you would think. versus you know, you there are examples plenty of examples of people consuming THC and CBD. And while it's an unpleasant experience when they've you know, accidentally ingested, you know, a couple 100 milligrams of THC. They're not like dying in adults, healthy adults.

Nick Jikomes 26:27

Okay, so So then in theory that sort of brings you to the whole Well, I mean, literally the sales pitch behind like E cigarettes, right that the idea would be, okay, we're using vaporization. So it's not combustion, we're talking about lower temperatures here, we are causing the nicotine to become to go into the gas phase. So you can inhale it, which is what the consumer is trying to do. But we're not producing as many of these nasty carcinogenic byproducts therefore, it's healthier. Is that a defensible statement?

Echo Rufer 27:01

I don't like the word healthier,

Nick Jikomes 27:03

it's less harmful, less harmful. Is that? Is that defensible?

Echo Rufer 27:08

I? Well, I mean, it depends on the other sort of flavor additives, and that sort of thing. I mean, there's a lot of unknowns associated with these flavor additives. And so you're not directly replacing what's in a tobacco cigarette, right? I mean, a lot of most flavors were essentially banned from tobacco cigarettes years ago. And so if you're now adding those into, you know, an e cigarette product, how do those compare? I mean, most, I believe that most companies that are now you know, selling products legally on the e cigarette market, will have done testing, and look to understand the risk from those other sorts of flavor materials. But I feel like if you look at the tobacco cigarette for being the number one cause of preventable death, your standard is pretty low. I mean, yeah, the worst of the worst, and like, is it an improvement? Probably, but is it 10% 50% 90%. And then if people if people change their use, so like, let's say, if you consumed, you know, a pack of of tobacco cigarettes a day, and now you take on the vape product that is no longer limited, where you can consume it, and you're, like, consuming it everywhere, where tobacco cigarettes are combined, and you're now consuming way more nicotine, you're consuming way up more additional flavor, you know, you have, you're maybe using a device that is not very well controlled, and temperature, you're producing some of these byproducts, potentially, you're starting to get into the dry hit situation at the end of a cartridge that leads to greater production of these byproducts because it essentially overheats. You know, are you starting to approach the risk, same risk as a tobacco combustion product. I mean, there's, that's definitely a possibility. And that's where a lot of the research I think is looking to go is to understand like how it is changing the product in the way that you've changed it lead to effects on the population and the consumption and all these other things that are not like direct toxicology that you're comparing in a, you know, in an in vitro, like cells in a dish or an animal model or something like that. Were you're comparing the exact same dose between the two.

Nick Jikomes 29:32

And when we talk about E cigarettes vaping nicotine products, they're, they're liquid. And so is that like, do they have to add something to get a liquid of the right viscosity just for the these devices to work? And in what are the what are the liquids typically composed of?

Echo Rufer 29:53

Are you talking about cannabis or

Nick Jikomes 29:56

still nicotine? Okay,

Echo Rufer 29:59

so nicotine. In general, in order to get the dose that you would be looking at which is is more comparable to a tobacco cigarette, they have to cut it back to I think it's a couple of percent is all that there is for nicotine, they'll have some flavor, and they have to use some solvent in order to dilute down because you can't do 100% nicotine, you know, somebody can kill people doing

Nick Jikomes 30:22

it so, so fit like the device, they could physically make it with pure nicotine, it's just that that would be so concentrated that that would be not suitable for human consumption.

Echo Rufer 30:32

I think it also has to do with the harshness associated with with nicotine to some extent, my guess is it would be a very sense very on, like, a not a pleasurable experience to do that. Again, I don't know, I've never vaped an e cigarette in my life. I have no idea. So, yeah, they do generally use like, I mean, I think 90 to 90 ish percent is probably a mixture of propylene glycol and vegetable glycerin are the most common solvents used in the e cigarette world. And what

Nick Jikomes 31:05

do we? Yeah, and what do we know about those solvents, propylene glycol, vegetable glycerin? Are they safe? Are they known to cause any issues.

Echo Rufer 31:14

So those are key. There have been some animal studies that generally show that they're not of the most toxic ingredients that are out there for a respiratory sort of toxicant. But when you start to test these solvents, at different temperatures in different devices, you do increase the likelihood pretty quickly on these two substances for the production of like formaldehyde and some of the other breakdown carbonyl oils that are observed with with these substances that are oftentimes not tested in the animal models, because the animal models will often just look at pure PG or pure VG without that temperature component,

Nick Jikomes 32:07

I see. And is there what kind of temperatures are we talking about here are temperatures that are going to be the ones actually use the most of these products, or, or above that,

Echo Rufer 32:18

um, well, I would say there's a range of products that are out there. The sum will, will be lower, there are others that have shown that it's not just you know what people are setting it at. But if they're, say, using their cartridge all the way to the end, they'll see in the last few puffs that they take, the temperature will jump up wildly. So um, there is a direct like linear response once you hit a certain cut off, and I don't know offhand what that is, where it starts to very quickly rise. And it's not that if you have a single device and you have it set at 180 degrees C it is always 180 degrees C you might hit me where you start to dry out the wick and then you end up with it, it'll pop up to 500 Celsius or

Nick Jikomes 33:14

so like just the way that these devices are physically built, they're immersed in liquid until that liquid goes down as the consumer uses it up and at some point the heating element is just kind of exposed and it's not immersed in the liquid and then the temperature shoots up and then what wasn't producing as many toxic byproducts before is now starting to do that because it's just hotter. Yes. Okay. And you know, if we if we think about cannabis, so how is like physically how is vaporized cannabis oil different to or similar to these nicotine vape products?

Echo Rufer 33:47

Yeah, they're actually very different. So I would say we can we as the cannabis industry can learn a lot from the e cigarette industry but we also have to do a lot of work to modify our approach to what makes sense for cannabis. So cannabis vape products are generally at least from what sold in the legal market within California and a host of other states around the country. tend to be mostly a cannabis extract. So that cannabis extract is something like you know, 80 to 90% of extracted from cannabis and you'll see on a certificate of analysis or COA that it is made up of your you know, THC or CBD, maybe some of the other minor cannabinoids. And then the other the remaining portion of that product will be you know, flavors or other added terpenes that are that are required to be added back after the extraction process because when you extract cannabis cannabinoids from the cannabis plant, those cannabis those can ammonoids are extremely lipophilic. And you will lose a lot of those terpenes that will volatilize off during the process. And so those have to be either collected and re added. Or also, there's a host of ways that you can purchase that volatile those terpenes essentially, that came directly from cannabis. And we've actually got a product that that does just that. So it's it's a hunt, it ends up being 100% cannabis, there are other sorts of products that, you know, botanical terpenes maybe use to add that flavor. And frankly, you know, the terpenes whether they're from cannabis, or from some other botanical source can have a significant effect on the experience.

Nick Jikomes 35:46

What can you just talk a little bit very briefly, because, you know, I've talked about this on the show before and people are probably mostly familiar, but what are cannabis terpenes? And you know, what are the cliffnotes there?

Echo Rufer 35:59

Um, cannabis terpenes are essentially secondary metabolites made by the cannabis plant, there's terpenes made by other plants as well. And those essentially provide a flavor and aroma component. In some cases, they can have an effect as well, to the cannabis experience.

Nick Jikomes 36:18

And how do we actually know that? What are some examples where they have an effect on the experience itself?

Echo Rufer 36:25

Well, there's, I would say limonene is one compound that has a very strong experience or immune, excuse me, a flavor commonly found in citrus, as well as its tends to be associated with some reductions in anxiety. Some, I would say Happy sort of effects. There's also beta chlorophyllin. I believe it's also found in Pepper, but as a common cannabis terpene as well, and it actually binds the CB two receptor, which kind of you could means you could call it a cannabinoid as well, but it is technically a terpene that of course, binding some of these other cannabinoid receptors, you would have an effect from that.

Nick Jikomes 37:08

I see. So some of these a subset of these cannabis terpenes are known to have physiological effects. Okay, do any of them have like clear psychoactive effects? Or is that mostly just coming from the THC?

Echo Rufer 37:21

Well, they're not intoxicating. I would say the psychoactive effect. This is one of those nitpicks in the in the world where we talk about psychoactive we actually mean intoxicating, so CBD is not intoxicating, but it is psychoactive. And I would argue that it's it's similar to some of these other substances like if limonene has the ability to reduce some level of anxiety and all likelihood it is also psychoactive.

Nick Jikomes 37:48

I see. And what do we know about the terpenes? In terms of any toxic effects that might have carcinogenic? Or just irritants? Like is there any anything to worry about in terms of cannabis terpenes and inhaling them?

Echo Rufer 38:02

It depends on the dose. So it you know what, I use a product that is 100%, limonene, 100%, beta Croscill? And absolutely not. And so it's really dependent. And it's really important, you know, me from a toxicological perspective, I think very carefully about these things and have actually published a paper looking at how to evaluate whether or not you're additive, whether it's a terpene, or a flavor or whatever, how to assess the risk from that, you know, the concentration that you desire to add. And, you know, I've also set restricted substances specification. So this is basically saying, you know, you've got these substances don't put it over this concentration, because remember, we go back to that risk component, the exposure or the dose is hugely important. So defining those is very important in determining the safety so you could I mean, you could run into a situation where, you know, somebody decided I really like limonene you know, and decided to add it at 10% to your cannabis extract, in all likelihood, that's going to be pretty irritating and harsh, and I wouldn't recommend it.

Nick Jikomes 39:23

What um, so people, most people consuming cannabis products most of the time are consuming it because they want to consume THC for the psychoactive effects. So what's the vaporization temperature for THC? And as you go from like, you know, the lowest temperature you could vape a THC product with and you keep increasing it. How much does the composition of the cannabis vapor actually change in terms of all the different chemicals that are going to be vaporizing across that temperature range?

Echo Rufer 39:50

Yeah, so I will say THC vaporizes out of so the The vaporization temperature tends to be different for different products. It's not just based on that individual THC. So what we see is that temperatures in which you can use a dryer or product, you can actually vaporize the THC at lower concentrations than you can at with like a concentrate vape as an example.

Nick Jikomes 40:21

Okay, so if you're vaporizing flour or physical plant material, you can do it at a lower temperature than an extracted oil.

Echo Rufer 40:29

Right? Right. So you can do that at like 185, I would say 200 215 Celsius hours ours, our concentrate device ranges from 220 degrees Celsius to 420 degrees Celsius. And we find that different products, really aerosolized better at different temperatures. And it will just be dependent upon the formula, I will say, generally, the terpenes come off, and you'll get more of a flavorful experience, you'll get more terpenes at that lower concentration, because they tend to have vaporization temperatures that are a little bit lower. But you'll oftentimes get larger hits at the higher concentrations, or I mean, excuse me, the higher temperatures, but not as much of that flavor.

Nick Jikomes 41:20

So I see. So from a health and wellness maximization or harm minimization standpoint, it would seem like you'd want to go as low as possible right around that 200 degree mark, because you'll you'll get the you'll aerosolized THC, you'll have a more flavorful inhalant, that's going into your lungs, because you've got a higher concentration of Terps. And you'll be less likely to produce toxic byproducts because the temperature is relatively low.

Echo Rufer 41:47

Yeah, I will say with a concentrate, you're not going to find a concentrate device that will vaporize it. 200 C. Access.

Nick Jikomes 41:53

Yeah. I suppose. I mean, a lot of regular consumers want to take a bigger hit. And that's just for better or worse what they want.

Echo Rufer 42:02

Yeah, yeah. Well, I mean, there's all the class like the big clouds is like a point I think that consumers actually evaluate. I mean, for me is the scientist over here is the toxicologist I'm like, why would you care? Like you're blowing all this stuff out in the air, right? Because whatever you're blowing out here in the air, like exhale, assuming you're paying to release all this stuff that you bought, you know, at not a cheap cost. Or like,

Nick Jikomes 42:29

I mean, yeah, I suppose what people are really buying is the ability to signal how cool they are to their friends. Absolutely. Okay, so So I didn't actually know that so you can vaporize cannabis flour at a lower temperature than oils? The oils are obviously more concentrated, they're gonna have a higher concentration of THC and other things. Um, what do we know about any, I don't know, any risks that are unique to vaping cannabis generally, or the concentrated oil specifically, I'm not talking about like additives or nasty stuff that sort of unnecessarily gets added in by the manufacturer. But for the the actual chemical components of the oil. Is there anything? Is there anything alarming there beyond just being mindful of, you know, if you vape too much in too short of a time at a high temperature, then you know, a lot of these things can become at least irritating.

Echo Rufer 43:25

Yeah. I mean, I would say THC and CBD while that is, you know, the intent of of using these products, they are also not risk free. You know, like as an example, unless a, there's some developmental effects associated with THC and CBD both. And so a pregnant women, woman or youth should really avoid these these products unless there's some, you know, risk benefit analysis, I would say done by a physician, because different from nicotine, I would say there is actually therapeutic value to these compounds. And so it ends up more of that risk benefit analysis versus just avoiding the harm because like, I mean, there is no medical use for smoking a cigarette, right? Zero. You could argue that's not the case for cannabis. And so ends up being like a specific case by case discussion with a physician and understanding those effects on a developing fetus or developing brain. And remember, our brains are developing until our mid 20s. They're not just done at 18 because the law says you're now an adult.

Nick Jikomes 44:38

Yeah. And I feel like a lot of people don't know that or they kind of overlook it. Yeah, these cannabinoids have very well documented developmental effects. So we can be completely agnostic about what we think about that good, better ugly but they are going to affect the the trajectory of your developing nervous system for sure. Yep,

Echo Rufer 44:56

Yep, absolutely.

Nick Jikomes 44:58

But okay, so what About there was this thing a couple years ago where a bunch of people got sick from vaping cannabis products, it was called vaping associated pulmonary injury, I think. So can you just remind everyone what exactly happened with that? And where did we land? What was going on there?

Echo Rufer 45:16

Yeah. So this is was I will say, that was a very scary time for me. There was a lot of conflation between, you know, it's E cigarettes with nicotine, it's cannabis, you know, what is the cause? And, you know, it was ultimately found out it was THC, obtained from informal sources, meaning the illegal market. And I think it was something like 60 people died and over 20 120 100 people were hospitalized. And what that seems to be a cause of is, you know, it was originally like, Well, maybe it's the pesticides degrading to hydrogen cyanide. While this toxicity absorbed does not look like cyanide toxicity, toxicologists just studied cyanide, there was some thought that maybe it's metals that are being released from the devices. That's also not the cause we know what metal toxicity looks like, this didn't look like it. Those things are not great, but it didn't seem to fit. The symptoms that were absorbed in individuals, it actually seemed to be this new compound that was put into vape cartridges. to dilute the THC, which is more expensive. It's Vitamin E acetate, it is generally recognized as safe for oral consumption. It's used commonly in topical products. But when added to the vape products, it seemed to do some really interesting things. And so there's kind of seems to be the cause seems to be multifactorial. The first is that vitamin E acetate seems to interact with pulmonary surfactant. Pulmonary surfactant is this jelly like substance that lines all of those alveoli of your lungs, those are like the gas exchange portions of your lungs. And they're required to modulate the surface tension to allow you to breathe without significant force. And the vitamin E acetate seems to cause a phase change. And that that pulmonary surfactant when it does that it made it much more hard, much more difficult for people to breathe. Next, the vitamin E acetate when vaped seem to produce a pulmonary toxicant called Qi tiene que tiene has a similar mechanism of appears to have a similar mechanism of toxicity as far as gene which is one of the classic pulmonary toxicants that causes significant edema in the lungs. So now you're adding additional water that's created by the key team component. And then I saw some very interesting research. And this is not published, it was just at a poster at a conference that I saw, but I think they're on to something that the vitamin E acetate seems to be creating an adduct. So it's binding to THC. And when it binds to THC, that means it's not available to get someone high. So if it's not available to get someone high, they're going to consume more because they want to get a certain level of high. It also reduces binding on the cannabinoid receptor which is what makes people feel the high that they want to feel so now they're doing that it removes the anti inflammatory effects that are you know, THC and CBD typically produce. And there's the question of whether this vitamin E acetate and THC adduct is actually causing toxicity itself. So, you know, this is some very preliminary research, but I saw the poster it was like, Oh, holy crap, this makes sense as to why this vitamin E acetate problem may well be associated just with THC. And you don't see the same effects on nicotine, because you don't have that same interaction between nicotine and vitamin E acetate. And people probably weren't using vitamin E acetate, nicotine.

Nick Jikomes 48:57

I see. So the problem with these cannabis products that were being vaporized, it was vitamin E, acetate, and sounds like there's multiple problems that are caused directly and indirectly. And it is plausibly true that there's a specific interaction that happens with THC and the substance. Yep. And so was this. Was this limited only to vaping products that were produced on the illicit market outside the legal market? Was it also legal products? Is Vitamin E acetate still out there in anything? And?

Echo Rufer 49:32

Well, it was entirely the illegal market. There were no confirmed cases that were from legally purchased products. Are there still cases I will say all of this happened and was being tracked late 2019, early 2020. Then this other little respiratory disease happened to pop up and the CDC stopped tracking so there was a significant drop. You know, people aren't in the hospital of dying, you do still see a case report pop up now and then. But I think I think somebody whoever was making these products with this vitamin E acetate kind of stopped, hopefully. And then there's a number of states that have added that to their kind of banned ingredients that aren't allowed in, in vape products.

Nick Jikomes 50:26

And so it sounded before, like you said, in contrast to tobacco and nicotine vapor products, where they sort of necessarily have to add some kind of solvent just to dilute the nicotine down and make the product consumer worthy. That's not really the case with cannabis. So people are generally not adding dilutions and other liquids, or

Echo Rufer 50:51

if if they do, in my experience, it's been very low concentrations. And so what will happen is, is when they extract from, you know, the plant, let's say you have a product, and you regularly have a certain concentration of THC, and your consumer knows that they're always going to get 85% thc. And this batch happened to come out at 88%. And you don't want that person to be thrown off guard, they'll sometimes add a diluent not Vitamin E acetate, at a very small concentration to adjust that. But in general, other than that, you're not I've not seen a lot of other companies I've worked with and you know, there are a number of people on the plaque, the Pax platform that we actually monitor that so I've had conversations with a whole host of companies that they're just they're not not adding these these at any meaningful concentrations.

Nick Jikomes 51:44

So in general, there's, there's no kind of, there's, there's nothing people should look at, or there's not a lot people should look out for, you know, I was gonna maybe ask you, okay, if there's, you know, XY and Z substances that often get added, is there one that is better than the other or less harmful? Or is there something people should look out for and avoid? Because it might be irritating, or potentially toxic or anything like that?

Echo Rufer 52:08

Um, I mean, I think what I would do, personally, is watch the device you choose and control temperature. I mean, you can ask about delusions in general, and whether or not they're adding them, I mean, sometimes it'll just be, you know, upping the concentration of terpenes. But I think from a, from a toxicological perspective, the way I like to see to look at things is everything in moderation, because essentially, when you're looking at risk, if you've got a dose in which an effect occurs above that a dose, and below it, there's nothing measurable and it's negligible, as long as you stay below that you're good. I would also stay in the legal market, look for a certificate of analysis, and not enter into the illicit side, because that's where, you know, it's kind of a wild west. And when I speak to, like, they're not adding these things, I am totally talking about the legal market, who know, I've heard some horror stories, frankly, about what's happening in in, you know, with people out there in their garages doing, who knows what, and then you know, they're buying like disposable devices where the air path passes over the like, internal electronics of a device. That means you can inhale all of the stuff that is typically inside of a device, which is all sorts of metals. And, you know, there's solvents used in the production of consumer electronics, and you know, that you would never expect so your device can be a huge factor they're buying from a legal market. You know, you're typically not seeing that, but it's a question to ask.

Nick Jikomes 53:55

So, yeah, so I mean, just to kind of riff on this a little bit more, and for you to reiterate some of that. So like, can you talk a little bit about the devices that you make you guys make at Pax and what you do to sort of ensure ensure your your vaporizing and volatilizing you know, only what's intended?

Echo Rufer 54:13

Yeah, yeah, so we actually do quite a bit. We have, we have two kind of lines of devices. ones are I actually have one of them here. It is a packed dryer of device and so essentially the flower is put into the oven. And you can consume that product. We also have a cannabis concentrate, device and product and oils that go of course into those pods. In order to protect the safety we one of our consumers. We one choose materials carefully, and that means there are food grade. Well I know food grade is not evaluated for inhalation. and it does have some requirements of avoiding certain harmful substances, some quality manufacturing requirements, etc. As well as we have what's called a restricted substances list. So that basically means I've defined I think it's over 400 ingredients or substances that could be used in the plastics or the metals or, you know, anything out ceramics that might be in that device that we tell suppliers, you're not allowed to have these here above a certain concentration. And the other thing is that we have a something like 500 tests in our manufacturing process to make sure that we like check for quality and you know that the battery is not going to blow up in your face, because you can worry all you want to about the, the diluent. And if the battery blows up in your face, you've got problem. Now from the oils, we also have a restricted substances specification with I think there's like 270 ingredients on that list that are not allowed to be added. We give concentration limits, etc, that, you know, like Vitamin E acetate, you can't add that, you know, I would say PG VG while they're commonly used for E cigarettes, with those higher temperatures required for cannabinoid vaping. Hmm, those do produce some of those those harmful carbonyl. So we want to avoid those.

Nick Jikomes 56:20

And again, just remind us so PG VG, it's this common. It's commonly used in nicotine, nicotine e cigarette products. And you said, if I heard you correctly, you said there's no obvious nastiness to it at a reasonably low temperature, but at a high enough temperature, it can produce some of these harmful byproducts. Can you remind us again, like approximately what temperature are we talking about?

Echo Rufer 56:44

I, I want to say it's at like four or 500, see, it starts to creep up, and then it rises pretty quickly. And you really high concentrations at 700. C.

Nick Jikomes 56:56

So it sounds like based on everything you've told me, like a rough rough benchmark is if you're below 400, you know, closer to 200. That's going to be the least possibility of producing some of these nasty bright byproducts. However, they're produced, whatever they're produced from, and once you get above or near roughly 400, that's when it starts to happen more.

Echo Rufer 57:17

Yes. Yeah. I think that's, that's fair. And remember, I'm speaking in Celsius, not Fahrenheit Celsius. Yeah.

Nick Jikomes 57:24

So so I'm definitely not going to ask you to like name names or, you know, point fingers at any brands or anything, but you describe how your devices are made? And why you make them that way. Are there any types of cannabis vaping devices that are constructed a certain way that are common out there that you think are not a good choice for consumers?

Echo Rufer 57:47

Yeah, I think the one big example is I know that there are some disposable devices that have the so there has to be a place where air comes into the device, and then where it leaves your mouth. So you have an air path, and you have a vapor path. So once it's produced the aerosol, and what's inhaling on the other side, a lot of these have an air path that travels directly overtop of like, the circuits on the inside of the electronics. So I mean, imagine vaping through your computer, like, that's what's happening with some of these devices, and how do you know that they couldn't be

Nick Jikomes 58:23

hot air is going over the physical, electronic components and metals and stuff. And it's entirely plausible that you're going to pick up at least a little bit of, you know, God knows what, yeah, yeah.

Echo Rufer 58:34

Well, I mean, I know even during the consumer electronics manufacturing process, there's pretty harsh solvents required is like, you know, putting together a PCB board, and you know, all of that stuff. So, you know, who knows what you're getting? I mean, maybe there could be some studies conducted on that, that maybe it shows the exposures are below some limit, but I wouldn't at this point where the research is, that's one thing I'd avoid. And then, you know, temperature, of course, is another huge one. And part of the problem for the consumer, I think, is, so we're talking about temperatures here, because we've characterized the temperatures of our devices. When you use a device that you buy from a dispensary, there's oftentimes an on off button. Well, what the heck does that mean in comparison to temperature? Who knows? And then you've got these others that might have multiple voltage, voltage settings, or wattage setting. I'm not an electrical engineer, I don't know how, you know, to convert those voltage settings to say this is going to equal this temperature. And I think, you know, what we showed in that publication that I was talking about with the thermal cameras, was that some of those voltages were the same. But there's other components of the device that affect what actual temperature is. provided. So I, I wish I had an answer for that one. But I guess it's ask your ask the look into what you're using and if they quote a temperature.

Nick Jikomes 1:00:14

Yeah, so you want to be able to easily tell what the temperature is, which should be common sense. You want to somehow verify if you can, that the temperature that's you're reading is the actual temperature. It sounds like the other big thing that you mentioned at the beginning was you don't want a device where that that air is passing over the, the, you know, all of the internal physical components of the device, right? Yep. Now, you know, ignoring sort of like health risks and and health stuff. When we compare smoking to smoking cannabis to vaporize cannabis, pound for pound, I don't know if anyone's done this. So so I'm just asking in general, if you were to I hope someone is on this. This is my question. If you if you vaporized, and then smoked the same amount of cannabis, the same starting material, you got the same amount of THC. And you line those things up as closely as possible pound for pound? Would the experience differ at all would THC concentrate? Like if you're causing X amount of milligrams of THC to vaporize? Versus combusting the same amount? Are you actually going to is your body going to see a different amount of THC? Is the experience going to be different in any way? People at least consumers report that it is people say I prefer smoking because it feels better, or vice versa, or whatever. Has anyone actually work that out in detail.

Echo Rufer 1:01:32

So there's some aspects that have been worked out. Now, I think there is a component of personal preference, but I'll talk about the resource that I'm familiar with. So they're not even thinking about the health perspective, but we're gonna say like some of those tar is what they used to call like the other stuff, right? That's not your your cannabinoids is higher with combustion. And that leads to an experience, there's also carbon monoxide that is produced. And that is not at the same level, innovate product. And so, I do think that there's also particle sizes that may differ between a smoked product and a vape product. And depending on those particle sizes, you may not actually absorb them, and you may not get the effect from them. And so that can change the experience. But I think on the carbon monoxide thing, it's interesting, I've got a hypothesis, this isn't actually been tested, but this is echos thinking. Because people like how a joint hits, you know, for whatever reason, they like the effect. And, you know, there have been some studies where you can can release some amount of THC, and they will experience an effect. However, they still prefer the joint and my I am convinced that they like the little bit of hypoxia that's produced by inhaling the carbon monoxide and they associate that with an effect. And that, you know, research is again and again shown that it is more than THC that affects the experience, even if you deliver the same amount of THC or have vastly different concentrations in THC. There's a couple of examples. Ethan Russo published a study within the last few months, I think it's it's something along the Nose Nose. And so that was based on terpene content. And they found that the subjective experience was more related to the that the perception of the aroma than it was to the THC concentration. There's also another really interesting study that was done by cinnamon Bidwell in Colorado. And what she did was she looked at two different concentrates two different flowers that were vaped, a different THC concentration. So he had 16, I think it was 16 and 24% thc. And then they also she also did a cannabis concentrate. I can't remember it was vaped or dab, but it was like 78% versus 90% thc. And what she found was that even though the blood levels differed a bit when people consumed and rated the level of high from each of those products, it was the same. So I think that what what that means to me is whether it's a combustion or a vape product, it's more than just the THC. All this other stuff matters. And if you're not burning a product, you're probably going to like the flavor although we're sorry. I'm never going to prove a product that intentionally as carbon monoxide to cause some hypoxia. So it's like a joint.

Nick Jikomes 1:05:06

Interesting. Okay, so that's a hypothesis. But you know, it makes sense. If you're causing some amount of hypoxia, that's, you know, you're probably gonna feel that. Right. Interesting. Um, is there anything else that you want to talk about that you think we didn't touch on? Just in terms of stuff people should know about? Vaping whether it's cannabis, whether it's tobacco or anything else? Um,

Echo Rufer 1:05:33

we could probably talk a little bit about I think, one interesting fact. One interesting piece is about combustion of cannabis, and the relationship to health risks versus the combustion of tobacco. And that cancer question,

Nick Jikomes 1:05:49

yeah, what's the overlap there? Because I know that on the one hand, you know, when they just look at, like epidemiological, you know, correlations and stuff, you don't see the same correlation with smoking cannabis that you do smoking nicotine, an explanation that people have often offered there is, well, on the one hand, we know that combustion is producing even cannabis is producing, you know, your aldehydes and your carcinogens of different kinds. Maybe there's some kind of anti cancer anti inflammatory effect that's canceling that out from the cannabinoids. But I don't know if that's been demonstrated. So what? Where do we land with that?

Echo Rufer 1:06:24

No, I don't think it's been demonstrated. And I do think that's still a really, you know, important question, because we don't see this link, even though we know it produces a lot of those same substances. So I do think that the cannabinoids could play a role. I think there's also an exposure piece, in that, you know, tobacco, consumers will smoke one to two packs a day, that's, you know, 10 to 20 cigarettes. I don't know anybody smoking 10 to 20 joint today. So I think there's the exposure piece. And so I would, I would love to see those data, you know, these, these, these long term epidemiological studies take a long time. But I think that's a really interesting, interesting question. And time will tell.

Nick Jikomes 1:07:11

I see. So So I guess the the moral of the story there is, as long as you can, as long as you control for tobacco consumption, and these other and some other things, there is not a link in association between smoking cannabis and lung cancer. So it's very different from the associations that we clearly see and know about with tobacco. And yet, we know that you're still producing from the combustion of cannabis, a lot of the same carcinogens. So there's some kind of mystery there.

Echo Rufer 1:07:40

Yeah, there absolutely is. And I will say that it's also interesting. There have been some studies that were conducted, showing or concluding, I don't think they actually showed it. But their conclusion was that I think it was stroke, or other sorts of cardiovascular like having heart attacks at a younger age. However, there were some very important, I think one of these papers is now actually been redacted. But they forgot to control for the fact of when cannabis consumption occurred, whether it occurred before the cancer after or the before the heart attack or stroke or after. Like you think that kind of be a big clue that my stroke was called by caused by cannabis if I started the cannabis consumption after the fact. So there's a lot of stuff out there that

Nick Jikomes 1:08:32

is there anything that you guys are working on at PAX that's let's do an exciting either on the device side, or on the consumable product side.

Echo Rufer 1:08:42

We've got lots of cool stuff coming out. But I don't want to, I don't want to break the break the excitement that will happen when we launch those products, I will say we just went live,

Nick Jikomes 1:08:54

are these new devices that you're talking about? We've got

Echo Rufer 1:08:57

a new device in the works, as well as some other new sorts of products that will that will be coming out. So

Nick Jikomes 1:09:07

like, like later this year? Yeah. Yeah,

Echo Rufer 1:09:10

I think so. I don't know the exact timeline is off the top of my head, but we've got we are extremely busy these days and working on all sorts of stuff. So yeah, very exciting.

Nick Jikomes 1:09:22

And just one more time I know that we've said this at least once or twice already. Let's say that you're talking to someone who is a cannabis consumer already. They already consumed cannabis some way maybe they vape it. Maybe they are you know, dabbing it. Maybe they're smoking it. What would be your recommended method of consumption to minimize potential health risks from a toxicology standpoint?

Echo Rufer 1:09:50

Yeah, I would say choose your product from a legal responsible supplier and consumer Boom, at the lowest dose that works for you. The other piece is that don't let THC concentration drive your, your purchase decision. There. Again, there are so much research out there that your experience will be better for the things that have a pleasant aroma for you, then what just has a high THC concentration, it's not additional value, you're not going to get higher as a result of a higher THC.

Nick Jikomes 1:10:31

But let's say let's say you know, they are an inhaler. They already are inhaling products, different ways. And what's what's, what would be your recommended way to inhale?

Echo Rufer 1:10:41

Juice packs product course.

Nick Jikomes 1:10:44

Okay, but but but more generally, like, are they vaping? Are they smoking? Are they

Echo Rufer 1:10:49

are they're absolutely vape vaping or smoking? I think. You know, there are now is there a comparison to be made between between dry herbs? And like a concentrate? Yeah, exactly. Sure. The data aren't there. I haven't seen one way or the other. You know, there's there's questions on you know, what are the flavors and ingredients and terpenes and the like added to a concentrate product versus the plant product. But the same thing with the dryer or is not everything is, is comparable. And because there's been so much what I would call like intentional breeding that is turned into genetic engineering of the plant, like what is out there for flour. Today is not what was out there 20 years ago, or even 10 years ago, or even five years ago. And so you're getting a little bit of the unknown associated with that as well. So making a conclusion between one or the other. It's hard to tell the data just are not available at this point in time to say one over the other.

Nick Jikomes 1:11:59

All right. Well, I think that's all I have. This has been a fascinating conversation. So thank you for joining me echo. I think this will, I think this one provided a lot of very tangible practical advice to a lot of people that interact with with this, this area of the consumer world. So thank you.

Echo Rufer

Thank you

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