Dr. Raber rejoins me on the Head Change podcast to discuss the controversial lab created cannabinoid called THC Acetate or THC-O-Acetate or just ATHC and the potential negative effects this molecule could have on human health and the advancement of the cannabis industry overall.
#THCacetate #ATHC #Cannabinoids #cannabis #thcoacetate #chemistry #EVOLI
23 min
CHAPTERS
Plant-Based vs Lab Created Cannabinoids [00:02:06]
Vitamin E Acetate and Ketene [00:06:19]
Hyperemesis Syndrome [00:13:04]
Too Much Of A Good Thing? [00:15:36]
Transcripts made possible thanks to a generous donation by Jeanne Nasarow of Bee Haven Hill Farms in Mendocino California.
FULL TRANSCRIPT:
Levi: There is an absence of good information out there right now on the internet about THC-O-Acetate which before our last interview I had never heard of. I've done some research sense then to understand how it's made, and we don't need to go into too much detail about how it's made specifically, but I'm really curious to get kind of a broader perspective from you a chemist and somebody who's been around the cannabis industry as long as you have about you know what it is, the potential benefits of it, you know? And the potential negative side effects that people could encounter especially when smoking it especially as that relates to vitamin E acetate and kind of the parallel there. I think it is important to break down a little bit further. And the people in the comments of the video that we made did have a lot of questions. Some people are comparing it to spice and K2, and synthetic marijuana. So I thought we could maybe address some of those fears and concerns and is there any validity to that or not? But one of the things I want to do on Head Changes this podcast is just present the information. And people can do what they want with that information. But, you know, I'm a pretty big fan of phytocannabinoids, man-made cannabinoids I tend to exercise more caution with. So, as far as I understand what this compound is, it's not a synthetic cannabinoid because it comes, you know, you take THC, you need THC to make it, but it is modified and not natural, you know. The plant does not produce THC Acetate on its own.
Jeff: [00:02:06] I think that's a great line of demarcation, right? Like Is it found in the plant? Is it native to the plant? Does the plant produce it and in this case no and I think it's really in our best interest and maybe a safety interest to draw the line there. If the plant hasn't produced it or doesn't make it, it's not found on it for any reasons, we haven't been consuming it before we should exercise great caution and that might be where the line is for, hey this needs real thorough full formal clinical studies. This needs to be understood much better before we let it go under our state based regulatory systems. You know, we only know what we know about cannabis because people have been using cannabis for so long. We probably stretch the limit of that with concentrates because some folks have been using concentrates for some time but certainly not as long as the plant use has been used, there has been hash around, but you know hash is a very different composition than what we see with you know, live resin extracts or sauce or distillates or rosin or anything else like that. So concentrates you know are probably as far as we might want to comfortably go to say these things are still found in the plant, found on the plant. Representative of what we see in the plant and concentrated forms offer benefits in terms of, hey, maybe I'm not consuming things like cellulose right? Or other types of components that are found in the plant which might lend towards more of what I want and less of what I didn't want. And I think, again, it does relate to, which way, am I consuming them, right? So, I've been combusting plant material for a while. Assume, we've been inhaling and consuming concentrates for a little less longer, but for a decent while, if they become more concentrated ,but look like the plant, great, that's probably more of a dose consideration. How much should I be using? How often should I be using it? Then is this a brand-new molecule or something that's made that hasn't been seen in the plant or hasn't really been introduced to humans in any fashion for quite some time. So I think what we see with you know the acetates, that's where that line should be drawn. These are not found in the plant, they're not native to the plant and you have to ask yourself, so what might be different about it? So why would I even consider making an acetate? It can change its polarity, it can change the absorption cross the blood-brain barrier and it may or may not be, you know, present solely in that acetate form when it hits the receptor or the body saponified, it splits it back into acetic acid and the THC molecule. The body is going to split it apart. We call those things prodrugs. Sometimes we do that for better absorptivity. Better you know deliverability of the compounds into the body system if we're providing an oral dosed product or something of that type, there can be reasons why, you know, pharmaceutical products have what we call this prodrug form. It's not the active ingredient but it is an ingredient that lended towards formulation towards better absorptivity or better you know ways of manufacturing so that I can make this in higher purities and get it into the body for these pharmaceutical reasons. We don't have so much of those concerns with THC. So the question is, can I perform the same tricks like making an acetate? Well chemically I certainly can. But the bigger question is should I? Should we go about it? Do we see significant benefits of doing so versus not? And I think in this case, I would say that the benefits do not outweigh, you know, otherwise or the potential concerns and harms. And the real easy harm to see is if I take any of these acetates and, you know, Delta 9 THC acetate, but I'm also hearing about Delta-8-THC acetate. So both of these, right? And I could even make a CBD acetate, they have a phenolic, you know, alcoholic group, and I can convert that to the acetate ester. And if I have this phenolic acetate, [00:06:19] we've learned from vitamin E acetate, that heating those up can release toxic molecules upon, you know, release and that molecule is called ketene. So, if I heat this in a vape cart and it breaks down and it only happens with phenolic acetates, I want to make sure to kind of clarify. It needs that phenolic group to facilitate the chemistry in any, like, favorable fashion, not that every esther couldn't potentially form the form that or acetate ester per se. But there are lots of esters and they were even asked if she was found in the cannabis plant so it's not just any acetate it, you know there's other acetates that might be there. Phenolic acetates will facilitate breakdown into forming the molecule ketene and ketene is a highly reactive species that we saw adversely reacting with folks lungs when we cause the EVALI problem. So, you know, chemists had really dove into that problem with vitamin E acetate. That was a specific phenolic acetate. And said, hey, look in this instance of phenolic acetates, I can see ketene formation upon heating, so that means I would never be interested in putting any at phenolic acetate like Delta 9 THC acetate or Delta-8-THC acetate or even CBD acetate in a vape cart or in any product that's going to be heated and then inhaled. Definitely not you know, worth any type of those transformations. There's no benefits and great potential harms to be found that way. Could you put it in an oral product? I would, I wouldn't say that you couldn't. I mean, you certainly can should you is a really, really complicated question because am I getting benefits from it. Do I know you know enough about this molecule or its potential changes to how the body reacts with it? That it Is better or worse than what I'm already starting with. We can formulate things with Delta 9 THC without the acetate function. Why do I need the acetate function there? I think you've gotten away from what's native in the plant and you potentially caused more questions and potential harm and concern, then we really should embark on today. I think that that's not going to serve as well. So, we kind of draw the line there and say, let's, let's stop here. That's not, you know, not worth doing because the harms greatly pretend, you know, could potentially greatly outweigh the benefits of any of that.
Levi: Do you know when THC acetate was first discovered? I looked it up myself and was getting kind of mixed history messages.
Jeff: I haven't looked it up, did you? I thought I thought some folks have made it a long time ago like in the 40's or 50's?
Levi: In the 40's is kind of what generally kind of came to mind. And now my understanding is heroin is an acetate of opium. Is that correct?
Jeff: Yep. So morphine is a phenolic group as well, and you turn it into heroin when you acetylate it. So the acetates of morphine or heroin so I think I mean, that's a bad parallel. I hesitate to draw the parallel because you're like, hey, I'm not, I'm not making heroin here but in a sense, you can say it looks like morphine's different animal than we see with heroin. And the addictive properties are very different and there are medical uses for morphine. But you know, he's really no, no medical benefits or uses for heroin and no one's ever. I develop that as a pharmaceutical, you know, we've gotten away from morphine and we make morphine analogues. Some of those are phenolic groups and you can make, you know, acetates and some folks probably have, but that's because maybe I'm, you know, using that in a formulation or I can patent it or I can get some sort of new piece with that one and there was a specific pharmaceutical pain interest for those. We now know that the whole class of molecules is probably not the best painkillers, we should use either. So you know I think it is a fair parallel to say, hey, morphine to heroin, that's the same type of chemical transformation I'm doing and you make that molecule much worse, you know, in terms of physiological pieces, when I do create that acetate, so maybe we shouldn't do it here because there might not be folks having problems with THC, but THC acetate and all sudden, we start seeing all sorts of problems and we're still at a delicate point in history. If we started seeing problems created by ourselves, there could be other states that say no, there could be states that start to say no more of this. We could roll back the potential for full Federal legalization, you know? And that's not what anyone wants, certainly not what patients want that are benefiting from what's there today. So when we see people benefit from what's here today, I'm always trying to, you know, make things better. Do things in the best interest of improvements, if there's, you know, economic or other efficiency improvements, absolutely all for it. But are their molecular improvements? In this case, I'm adding more stuff to it, so I've got to do some other chemical transformations, so the economic argument just starts to go away. I've been able to formulate with all the phenols in THC and CBD already, so I'm not going to see any benefit there. It's new, like okay, that might be a curiosity of interest but I think regulatory, legally, physiologically, safety-wise it. There's not enough curiosity interest there to kind of drive down the potentially harmful path.
Levi: Well, I think I think you probably hit the nail on the head. I mean the interest in THC-O-Acetate from what I picked up as maybe there's some genuine interest of. Hey, if this is our medicine, is their medicinal value to this that could really be of use? I think that's always a worthwhile exploration, but I think it's drug culture that really is always going to want to go down. There's always going to be guinea pigs, raising their hands. You know, you can go on YouTube right now and there's guys dabbing, you know, THC-O-Acetate and doing reviews from, you know, probably illicit sources or you know the Hemp Act has really, the U.S. Farm Bill has kind of opened up this avenue of molecules on the market that are, you know, legalish. And I think probably right now THC acetate and some of these are so new and that maybe they haven't actually been regulated specifically. So it's kind of a free market out there right now and people are signing up to be guinea pigs and, and hey, do what you want. You know, it's your brain cells, but I would myself exercise caution and I've always felt like if it's from the plant, you know, and yeah I get that dabbing distillate and live resin is kind of intense but at least it's from the plant you know and it just cannabis and you know I'm not too concerned about that. I think if you're doing it all day every day, your tolerance, if nothing else is going to be completely destroyed and you're going to spend a lot of money just to get high.
Jeff: Yeah, that means you probably went overboard. I would caution you that you might be on the path to [00:13:04] hyperemesis syndrome and you don't want that. So you can tip your cannabinoid system, your endocannabinoid system out of whack with too many exogenous cannabinoids too, so there's its balance right? Like so could I dab? Sure. And maybe there's great reasons to do so. Immediate pain relief, you know, even you know people are like hey I just like that version of it. Okay. But if I start to go and it was, you know, once a day and now it's 50 times a day, every day, all day and the amounts are larger. Maybe I need to take a self inventory of that and say whoa wait a minute. I've gone down too far down the path. And I really need to kind of dial that back. Take a break, wash everything out and you know, go slower again, and I can still get back to that physiological effect that, you know, probably took me on that path. But in a way that is not going to send my body out of balance because I can go out of balance with too many exogenous cannabinoids. And I would really caution against dabbing these acetates because, you know, the heat is higher, typically on the nail or perceived to be higher on the nail. We don't really know all the temperatures inside the vape devices but You could definitely see the same types of decomposition chemistry's forming ketene and it would be horrific that someone said look I've been dabbing on, you know, I'm on this material for x amount of time and I got EVALI and I never used a vape cart, we're like, oh, like you know, that would be the unfortunate confirmation of those types of studies that have seen that and it would really be horrific and I would hate to see anyone inadvertently go down that path but you very well may be on that in a more rapid sense and you would from some of the vape carts.
Levi: Right. Yeah, I mean, you know, I love dabbing. I mean, I've got literally, I've got a dab rig right here, you know I have no problem with cannabis concentrates, you know, I love rosins and all that and but I think you know, when you do start concentrating these compounds and then your tolerance gets so high. I think maybe the dab culture is a little bit of a reason why THC acetate is gaining popularity because people's tolerance is so high now, they do need, you know, the next thing. But actually, your tolerance of you taking a little break, taking a couple days off, three days off you know your tolerance usually starts to level out. Take a week off and they really level out pretty quickly in my experience.
Jeff: Right. It doesn't need too long. Yeah, yeah I think that's what most folks will say that too.
Levi: So I just encourage people and just keep it real, you know, like we promote cannabis on the show and I love the therapeutic potential, I love the psychedelic potential, I love the recreational potential. I don't shame cannabis at all but you know there can be [00:15:36] too much of a good thing and once we start getting into synthetic compounds and man-made compounds, I think exercise and some caution is warranted. And I think there's kind of this innate desire in man to improve upon nature and now and then, you know, I even go further even the, my you said, we're when there are cannabinoids or even terpenes in cannabis that show up in very small amounts. I always exercise caution when concentrating and smoking. You know, [00:16:04] CBN is a good example of that, you know, you typically don't find a lot of CBN and flowers unless it's really old. But now we're concentrating on CBN products. Personally, CBN doesn't work for me. It makes me really lethargic and kind of feel like a zombie the next day and I wonder if there could be a CBN, you know, overload?
Jeff: Yup, it's a different cannabinoid and it may act on the system in very different ways, right? And we haven't seen products before with large amounts of those. So, you know, you might have had a trace amount of it or there's some that forms in combustion of your plant material, but have you had a hundred milligrams of it like that? You could have now if you took it, or did you take it in an oral dose like that? No, so it is something, you know, quite different and I think, you know, you were saying there's [00:16:47] medical perhaps interest in the acetates and I believe there could be but let's go down a clinical study path with those. Let's understand that and the potential harms in those types of formulations. So it might be super effective in a tablet for folks with pain or, you know, other types of serious deleterious ailments, but it doesn't mean that we should be, you know, dabbing it or putting it in a vape cart, I really think if anyone is now brave enough to want to play around with those things, I understand the spirit, I, you know, I think there's a part of all of us that really loves that part of the spirit.
Levi: I'd probably dab some. I dabbed some [00:17:27] delta-10-THC recently, that's a man-made cannabinoid as far as I know. I'll Lewis and Clark it every time but I'm not going to, you know, that's not going to become my regular.
Jeff: And it's not without risk, right? It can be deep one time can be, you know, too much for some folks. Yeah, you know, I think it's really about knowing yourself, knowing the risk that you're taking. I think informed risk is really part of what we're all arguing about, right? Like, I can inform myself enough about cannabis and the products that I feel comfortable taking. Is the government telling me better than I knew, before saying you should never have it. I think they were wrong, but at some point they say she probably shouldn't have these because we really don't know about them. They probably will be right. So there's a continuum there, you know, I'm libertarian minded, like everybody should have their choice and make their own choice, but only when you can make it from an informed perspective and informed is a difficult, if not impossible word to define for each and every individual, because, you know, our backgrounds are different or level of understanding and education on certain topics is going to be different and it becomes really challenging to say like what is in form for everyone because everyone's In their own, right? You can't say like hey everything out here is fair game. Have that? It will definitely see people getting hurt which we saw with EVALI. So there's, you know, there's a fine balance there and I think we have to exercise a little bit of caution until we're cemented in knowing we haven't had this opportunity taken from us. So if we can walk with a little bit of, you know, err on the side of caution, maybe we need to be careful before we know better, like you said, there's always going to be folks that will say, hey look, I've done this but they also might be folks with physiology that's very different than others that would not do it, and if they tried it once might have those horrific effects, right? You know, I think it's really hard to overgeneralize and think that anything is right. And what we see is tons and tons of over generalizations to try and make a, you know, legal sound bite, or some sort of, you know, position on a pulpit that says, hey here, let's just do this and it's just not that simple, unfortunately.
Levi: Yeah, everyone everyone is as unique and their physiology and and their mindset and we respect all views, but I do think that staying plant-based and, and buying, especially inhalable products from reputable sources and websites and if you're going to buy online do your homework on these brands because I can promise you coming from the traditional market myself you know, there are good operators and people that lab tests and really, really care about the products they are making and then unfortunately they're people that really don't not exist at all levels of manufacturing unfortunately. But you know, we do need to check, you know, human nature in that regard because I could definitely see people spiking vape carts now with THC acetate to increase the potency, and then cutting the regular THC extract because that is expensive with something else. You know, if not vitamin E acetate, something else people are going to be looking to increase profit margins.
Jeff: So I would think THC acetate through the other, you know, cannabinoid acetates will be more expensive than just the cannabinoid though. At some point, you know, it's a raw material for this piece. It shouldn't be cheaper but you know and I don't think it packs so much more of an impact that it would overwhelm if I added five or ten percent, it would be worth it. So I think we'll physiologically see that check where we wouldn't have that potential problem, but any lab will take a sample from you and inspect it. I don't think many of them care where you got it. They're all interested in protecting your health as well, and if you hand it to them and say here I need this tested, it's your health and you know, you only get one shot at the whole road here, so it might be worth that $50 test or, you know, a little bit of a even a hundred bucks to say look please just tell me I'm not going to hurt myself with this or is this a supply chain I can trust? It is probably worth it if you're going to rely on that supply chain for quite a while.
Levi: Yeah, back when I ran my little collective, my prop 215 collective and patients would email me -- Hey, have you tried this product? What do you think about it? And there's so many products out there.
Jeff: No, I haven't tried them
Levi: I would always encourage people to lab tests and a lot of them actually really would. And, and I think, I think it's a worthwhile thing to do to make sure that, you know, what you're consuming is, what it says it is, and it isn't harmful, because there are shortcuts that can be taken and, you know, very interesting stuff. Jeff thank you so much for coming back on and bringing in some more clarity around THC-O-Acetate. And I know that people are very interested in this molecule, so you'll probably be hearing from me again. And yeah, we can bring you back for a third encounter.
Jeff: Happy to answer all these questions. So you know I'll encourage everyone to ask away right? And then we'll try and answer them there but I'd be happy to have another session dedicated to specific questions especially if certain ones keep coming up so that we can further the discussion and make sure everyone's got the best possible information at least all of what we would know today.
Levi: Yep. That's why I love having you Jeff. And thank you very much again for being here on Head Change, have a great rest of your day.
Jeff: Thanks, Levi you have a great one too, take care.
CBN [00:16:04]
Medical Properties of Acetates [00:16:47]
delta-10-THC [00:17:27]