In recent years, a number of new synthetic cannabinoids such as HHC, HHC-O, H4CBD, HHC-P, HHC-PO, THC-B, THC-P and others have appeared on the market of psychoactive substances. Where they come from, how they are created, whether they have a therapeutic potential and what is the risk of using uncontrolled substances, I talked with Ing. Petr Palivec from the University of Chemistry and Technology in Prague.
In episode 58 you will learn
- What is the difference between synthetic and natural cannabinoids
- How many synthetic psychoactive cannabinoids may yet be created
- Whether synthetic cannabinoids have therapeutic potential
- What are the risks of using psychoactive substances from an uncontrolled market
- Whether new psychoactive substances can simply be banned
Podcast transcript
The podcast has been machine translated, please excuse any transcription errors.
Welcome to another episode of the Hemp Podcast. This time I'm reporting from Ostrava, Konopex is here and my guest today is Petr Palivec from the University of Science and Technology. Welcome, Peter.
Hello, thank you for the introduction. So as you said, I'm from the University of Chemical Technology in Prague. I'm currently studying for my PhD there, and as part of this study I'm working on new psychoactive substances, so mainly their metabolism, but also their, let's say, medical use, their analysis and also their synthesis. I actually work there in the laboratory of forensic analysis of biological active substances under the supervision of Associate Professor Martin Kuchar. So I came here to Ostrava for Konopex, where today I will participate in a panel discussion about new synthetic cannabinoids, such as HHC, THC-P, HHC-O and so on.
Which is great because that's actually the topic of our conversation. We've already met actually at Cannafest in Prague, where there was a panel discussion about HHC. I think it was specifically focused on HHC. I was already thinking at the time that I would love to talk to you about it because you understand it much better than I do. And could you give me and the listeners of the Cannabis Podcast a little bit of insight into what this HHC is, how it's created. And actually not just HHC, but all of these, let's say, alternative cannabinoids. So could you give us a little bit of an idea of what it is.
So actually HHC chemically is a phytocannabinoid that is similar in structure to THC. It's also what THC is made from. Actually, THC, that's the acronym, is tetrahydrocannabinol and HHC is hexahydrocannabinol. So actually the molecule of the substance contains just one extra hydrogen molecule. That's tetrahydro, hexahydro. And actually the effects, as far as HHC and THC are concerned, are very similar, and for that reason, there is actually also, there was a substitute for that THC.</p
HHC is already banned at this point, actually some other derivatives are banned with it, if I'm not mistaken. But interesting you said that actually HHC is then made from THC, but the THC is obtained how?
Actually, when you make the HHC the way it's made, it's a two-step synthesis let's say, and actually the feedstock, what you start with, is the CBD, which is isolated just from the cannabis plant. So first we take the CBD, we make the THC out of that, and then we convert that THC into that HHC by what we call hydrogenation.
So actually in that production you have to go through that process of just making that THC.
Yes.
So you have to do it, it's actually relevant nowadays whether you have to do it in the conditions that you license or not. It doesn't really matter. I've heard that you can actually make that HHC in other ways where it doesn't have to actually be cannabis at all. Is it possible to synthesize that cannabinoid in some other way?
Actually, if we wanted to do it in the lab, there's an awful lot of ways we can synthesize that molecule. And a lot of them don't actually include any of the structure of CBD or THC at all, that we actually get the HHC directly by some process. Now, I don't know what it's actually like if we wanted to do it commercially on a large scale, because of course, I guess if someone discovers the process, they're not going to want to share it too much, but I can imagine that it would actually be possible to produce the HHC in some way that avoids the THC.
Well, I don't know if it's possible to do it commercially.
Yeah, yeah, yeah. Well, we do have HHC, but we have it today is THC-P, I don't know, CBD, H4CBD, CB9, CBG9, you just clouds. those actually alternatives, which is basically what the people who warned against, who said, let's not ban HHC in general, because a lot of other cannabinoids are going to come, that's basically what's happening. What's the difference in production, actually? So is it about needing that THC again or is there a different process?
So I would actually divide the derivatives into sort of two groups. One is HHC, THC and THC-P and such. And then there are those derivatives of something, something with an O at the end. And actually when we have, let's say, THC or that HHC, those are the substances that are made from CBD. And from those we can then make, say, THC-O, HHC-O. And if we actually take the structure of that substance, that substance has some sort of carbon chain in it. And that carbon chain has a length to it. Usually that length is between three and eight carbons, and then we actually get other derivatives based on that by varying the length of that chain, like things like I said CBD, THC, HHC. HHC, these are all derived from five-carbon chains, which are the most common.
And then we can actually have, in addition to the five-carbon ones, we can actually have those other lengths, for example, THC-V and the HHC-V derived from that, Delta-8 THC-V or HHCV-O, all the other derivatives, those have a three-carbon chain. We can then have those derivatives THC-P, HHC-P, they have a seven-carbon chain and that way we can change the actual length of that chain. And actually those natural cannabinoids have, as I said, the five carbon chain and those other cannabinoids are also found, let's say, in nature in some scale, but when they are then produced, they are usually produced from some terpenes by some other, multi-step synthesis.
And so actually the THC-P, although it's somehow natural, what's actually sold afterwards is made synthetically in some other way than the normal HHC or the normal THC.
But the end product, if I say HHC, THC, THC-V, whatever, the end product should always be the same. If I make THC synthetically, let's say, it's the same as if I isolate THC from a plant, right?
Yes, the moment I have the pure substance, the substance doesn't actually remember where it came from, whether it was from nature or some synthesis. And now the substance is always pure. Or I know that maybe you're definitely in the lab, maybe you've got some products with the HHC, let's say. Is it actually possible to achieve in that commercial production, is it possible to achieve to have really pure HHC, or there, or any other cannabinoid, is it possible to achieve to have it pure. So it's challenging, it's more expensive, it's...
So is it mostly pure, or is there usually maybe, say, one percent of something else?
Actually, in my experience, in those HHC samples, there was usually some 4-5% impurities that we couldn't actually identify, it was some other cannabinoids, but anyway, pure you could do it, but it would be much more expensive. Which I guess somebody... Mostly, mainly actually by the fact that there's a lack of that legislation to look after that, that purity, so most of the time it, or the sellers didn't, I don't want to say, didn't address it completely, but...</p
So unless of course there's some sort of standard, some sort of regulation on how to sell something, there could be cinder in the rolls. That some retailers would just handle it differently. But let's leave the vendors to the vendors, that's not what we're primarily interested in. I'm wondering if... Actually, how many more variants, some alternatives that will be psychoactive, that will pretend to be a cannabinoid, or will it just be a modified one, how many more of those might be created, for example?
So what I would answer that simply, a lot. It's a really large amount. It could be hundreds to be precise, it could be thousands, depending on the creativity of the people who are inventing these new structures, synthesizing them.
So what I'm wondering, and I think a lot of other people may be wondering this, you said that in the cannabinoids, the synthetic ones and the normal ones, that the natural ones have three carbons and what's based on them has three carbons. Let's put it in layman's terms, let's leave some room there, that's not entirely accurate. But I'm wondering now if I could say that the five-carbon cannabinoids are mostly synthetic. If I could do in terms of legislation, say that five-carbon anything that has five carbons, no, and thereby basically prevent the creation of other synthetic cannabinoids. How do you think that would work from a chemist's point of view, if there's a solution that could prevent the creation of more synthetic cannabinoids?
That's very complicated.
So otherwise still. There's a risk that if we were to ban, say, some derivatives of a substance, there's a risk that we include some substances that are needed or that are commonly used. So that we don't, say, ban another HHC or some synthetic cannabinoid as a derivative in order not to ban, say, edible oil?
Well, I don't think it was that simple, but it's more the fact that there are an awful lot of possibilities where you can modify that molecule. If we wanted to actually ban all of those possibilities, then yes, we can actually ban some substances that are not psychoactive at all or might have some completely different medical use. Actually, what the current legislation does, and as I was talking about there being some chain that has some number of carbons, I was actually talking about the substances that are currently appearing, some three carbons to just eight carbons, that's let's say the basic series that we have here. But of course we can make changes in that chain, not only in the number of carbons, but in how it is branched, it may contain some other elements besides carbons, the whole molecule may be substituted somewhere else, and all these substances may or may not be active.
So if we wanted to actually ban cannabinoids in general, we would have to really ban some basic structure, and by doing that we just ban, let's say, an awful lot of other potential molecules that may have some other use.
I understand. So it's not quite as simple as just saying anything that starts with HHC, or that's HHC-P, is just going to be banned.
It's not simple, no.
We agreed that it would probably be a good idea to set some regulation, some rules to that, if these alternative cannabinoids or alternative psychoactive substances based on cannabinoids were to be made available to adults here, that it would be good anyway to have some regulation, some rules under which they could be marketed, because it's what you mentioned, that actually in some of the products there was maybe 5% of something else that maybe wasn't fully known. That is certainly not good, and I think it should also be said that those synthetic cannabinoids actually lack the other substances that are in natural cannabis, for example. We now know that when we use cannabis, whether from a medicinal point of view or for recreational purposes, it is a set of substances that interact and modify each other in some way, if I am not mistaken. And I'm still wondering whether synthetic cannabinoids have medicinal potential or whether they can actually be used for pharmaceutical purposes as well.
Well, actually, if we have synthetic cannabinoids like the HHC, THC-P here, then these cannabinoids may have potential and especially the HHC derivatives, the hexahydro ones, actually because they are much more stable as opposed to the tetrahydro, THC derivatives, they don't degrade over time, they don't break down, and therefore, by making the medicinal products more stable, there is no risk that they will either lose their effects over time or that there will be some other products that could be harmful in some way. So actually the potential here is high, and for that reason as well, it just needs to be regulated in a sensible way and not by actually throwing all these derivatives off the table, saying they are banned and nobody will look at them anymore.
Can you imagine a situation where, say, HHC can be obtained relatively cheaply and let's add terpenes and all these other substances to it. We know for a fact that this HHC, let's say THC, as the main cannabinoid of cannabis, is somehow already tried and tested. We know roughly what it does to people even after some extended period of time. Is it safe to say that HHC would be equally well-tested, or that we could assume that its effect even over time would simply be the same or predictable?
We can actually assume, based on the fact that HHC and THC have some similar structure, that they will also have a similar pharmacological profile and metabolism, but we can't actually ever be sure. Actually, to take an example, when a new drug is being developed, which in theory we are talking about here, that those cannabinoids like HHC could work as a drug, before that drug can be circulated to humans, it has a whole series of clinical trials to go through and it is called a 'drug trial'. There's a whole series of preclinical studies where they're first tested on cells, then they're tested on animals, then when they actually go through the first phase here, then they go into clinical trials where they're tested in several phases again on humans, first on a small group, there's side effects, then they're tested actually on dosage, etc.
There's a whole series of clinical trials where they're tested on humans, first on a small group, there's side effects, then they're tested on dosage, etc.
And it takes a few years, up to decades and an awful lot of those test subjects and those actually patients before we're actually able to say, yes, this substance is safe, it has these sort of side effects, long-term use can cause this and this and this. And even after the substance is actually put on the market, it's actually monitored for a few more years afterwards actually backwards when there are some of these side effects here, some of these toxic effects and so on. And we just don't have that with this HHC and these new cannabinoids here. We can say like yes, it's probably the same, but we just don't have those clinical studies here, we don't have any history of use like we do with the THC, so we can't say for sure about that.
Of course, so with the THC one, actually the trials here are basically like done. So that's good news for THC. However, I'm still intrigued by, like, how HHC is, it's said to be stable, and its proponents are pointing to its medicinal uses for that very reason. medicinal uses point a lot to that aspect of it. Like this, THC after a while starts to break down into just some other substances and other cannabinoids for example. HHC stays, there's a comparison to be made, like THC will break down in a year, yeah, HHC will last two years, let's say. Or if you can say, if we're just going to put HHC in a jar, in the fridge, in ten years time there's still going to be HHC, whereas there's nothing left of THC. Is it that much more stable, or is it even possible to put it that way?
You can say it's like that, I'm sure they won't tell you the exact numbers, but it's significantly more stable, and that's actually because THC can oxidize to CBN, in between what HHC can't oxidize. So actually, in terms of like the, let's say, the degradation form, that's not a concern here. I'm sure there may be some other form of degradation, some other mechanism that they will actually understand, but not this same oxidation that is the problem with THC right now.</p
There is a lot of talk about natural cannabinoids, synthetic cannabinoids, and semi-synthetic cannabinoids. Let's say we're clear on natural cannabinoids. If I take cannabis, squeeze out of it, perhaps mechanically or with an extractor, the cannabinoid without changing it, I have a natural cannabinoid. How would a semi or semi-synthetic cannabinoid be characterised? Because a synthetic cannabinoid is something that I make in the lab from something other than cannabinoids. Am I saying that correctly or could you be more specific?
That terminology is not that settled and it's more of a wordsmithing thing. In terms of how that term synthetic and semi-synthetic is used, we know that we've had those natural cannabinoids THC, CBD, CBN, CBG and so those are the natural cannabinoids that are found in those plants. But we can take these things and isolate them from nature or we can synthesize them. And that's when I made this natural cannabinoid synthetically and it's synthetic. What we can also do is we can actually take a portion or take a natural cannabinoid, like that CBD, and make that HHC. And at that point we can say that it's semi-synthetic, that we're actually changing something that came from nature by some synthesis.
But there's actually a problem here that synthetic cannabinoids were referred to as, were called substances referred to as JVH, and they were often so-called full agonists of the CBD1 receptor as opposed to the known cannabinoids which are partial agonists, were much more potent and could cause overdoses. And, in fact, in the Czech Republic there have been several cases of overdoses or fatal overdoses of these synthetic cannabinoids. But the fact that we have actually started to label these substances as synthetic cannabinoids does not actually mean that everything we do synthetically is bad.
And I think part of the reason that actually the word semi-synthetic cannabinoids started to come up is that actually the person is like yeah, it's done synthetically, but it's from natural substances, it's not from that lab. But it's actually not a bad thing that it's from the lab. Actually, it really depends on the final substance, what we make, what the effects are. So I guess that's the terminology.
But then again, in complete layman's terms, when I'm on natural cannabinoids or straight like cannabis, there's no threat of any substance that could kill me. If we're talking about that we know that there's actually no known deaths from cannabis use. Whereas in the production of those synthetic cannabinoids, or even semi-synthetic cannabinoids, that process, that synthesis, may produce substances that we may not know about, that may be there in trace amounts, but in some cases may be there in higher amounts, or may be much more potent. So, even if they are there in trace amounts, they can have an effect on a person's psyche or on a person's health diet in general, even perhaps with fatal consequences.
Yeah, that's true, of course.
Of course. Good. I think we've covered that topic in a fair amount of detail. Can you think of anything else you'd like to say about it? I mean, you've had experience with it, or you've encountered it sort of more often than I have, I guess, I've encountered the synthetic cannabinoids sort of more vicariously, but I think we've said about everything around that.
So I think we've kind of covered everything.
Thank you very much. If you want to ask any more, have any additional questions about it, feel free to email me and I'll try to ask Peter vicariously and answer maybe your questions. I thank you so much for being a guest on the Cannabis Podcast and I wish you a great time. And to you, the listeners, have a great day, bye.