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In recent months, onlookers have seen high-profile, high-inducing cannabinoids divide the hemp industry. As a growing number of states step in to regulate these controversial substances, such as delta-8 tetrahydrocannabinol (THC), several cannabinoids are joining the fray. A semi-synthetic cannabinoid known as THC-O Acetate is an eye-catching substance.

To learn more about THC-O Acetate, Cannabis business time, Cannabis dispensary and Hemp producer spoke with certified neurologist Ethan Russo, MD, who has spent the past 25 years studying the medicinal aspects of cannabis and the endocannabinoid system. That includes more than a decade as a senior medical advisor to GW Pharmaceuticals, the company behind Epidiolex, the only cannabidiol (CBD) drug approved by the U.S. Food and Drug Administration (FDA). Dr Russo is now CEO and Founder of CReDO Science, a company dedicated to making cannabis safer and better.

Photo courtesy of Ethan Russo

Dr Ethan Russo, MD

Jolene Hansen: The hemp industry is witnessing a proliferation of controversial cannabinoids, including THC-O acetate. Does this surprise you or did you see it coming?

Dr Ethan Russo: Plus the latter. All this nonsense about these synthetic products, I see them as a byproduct of the ban. If there was legalization of cannabis products with proper regulation, I don’t think all of this would happen. Maintaining the ban has essentially been a catalyst for this kind of product development that people would like to think of as legal, but clearly are not. THC-O acetate certainly falls into this category.

JH: So what is THC-O acetate and how is it derived?

ER: It starts with tetrahydrocannabinol, better known as THC. It is the natural product that is the main psychoactive component of cannabis. THC-O acetate is a so-called semi-synthetic derivative, or the like. Through a chemical process using a very toxic chemical called acetic anhydride, you can turn some of the delta-9 THC into THC-O acetate.

Why would anyone do this? Well, one of the reasons would be that – apparently – it’s two or maybe three times more potent than THC. Is it useful? I’m going to say no, and the reason is that THC is what is called a weak partial CB1 receptor agonist. Now, let’s break this down: low is easy to understand. Partial means that its binding is not very tight. Agonist means that it stimulates the CB1 receptor, which is the mechanism of action that produces the high of THC, as well as many of its therapeutic properties, including pain reduction, and so on.

Powerful sounds great. But it’s a system in the body – the endogenous cannabinoid system – that works with a lot of subtlety. In other words, what you need when using a drug to stimulate the system is a little nudge, not a violent push that comes from something that is much stronger than THC itself. . So powerful is not necessarily better.

If something is less potent, you can overcome it by using a higher dose. But for many medical purposes, fairly low doses of THC are what is needed and desirable rather than higher doses, which will be associated with side effects more than benefits.

JH: When we talk about the people in the hemp industry who produce THC-O acetate – and maintain that it’s legal because it comes from hemp – do they create it from delta-8? THC?

ER: Well, they could. Normally one would make THC-O acetate from delta-9 THC. So it could be from garden strain cannabis that contains THC. If they were making it from CBD, I think they would have to convert CBD to THC first, which can be done in the presence of strong acids. But even this process is not legal, despite the fact that people think it is.

Many companies claim this is legal based on the 2018 Farm Bill [The Agriculture Improvement Act of 2018]. I do not know that [the farm bill] supplants the Controlled Substances Act of 1970, which basically said that there are parts of the cannabis plant, like the stems, that aren’t necessarily illegal on their own, but once you try to do chemical extractions on them or to change them to something else is illegal.

Additionally, delta-8 and THC-O acetate would both be considered analogues of delta-9 THC. There was a 1986 law – a nasty law passed by Congress called the [Federal] Analogue Act — that says if you make an analog, a molecule similar to something that is already illegal, ie delta-9 THC, that the analog you made is also illegal. … So no one should be under any illusions that this is all legal. Many of us think that is absolutely not the case.

Now, there’s one more wrinkle here: The process of making THC-O acetate is inherently dangerous. Acetic anhydride which is part of the process is extremely flammable and potentially explosive. This is something that needs to be done in a technical lab with an extractor hood [and] no exposure to humans.

“So between the danger inherent in the manufacturing process, the potential toxicity of the product, and its illegality, I have to recommend people to forget about it. It’s just not something people should try.” – Dr Ethan Russo, MD

Beyond that, there is so little that has been done with THC-O Acetate that I have no guarantee that it is not potentially toxic in some other way. Perhaps it is not properly broken down by the liver and can build up. While it’s two or three times more potent than THC, it’s an immediate recipe for potential serious side effects. [Note: Dr. Russo stresses that THC-O acetate’s potency is not yet known.]

So between the danger inherent in the manufacturing process, the potential toxicity of the product and its illegality, I have to recommend people to forget about it. It’s just not something people should try.

JH: Do you see any potential applications for THC-O acetate?

ER: I cannot rule this out. Again, his enhanced potency – putative enhanced potency – may or may not be of use. If it went through the normal process of toxicological testing in animals, and then through the usual processes of studying humans in clinical trials, it might have an application. But it is more likely that the benefits will be outweighed by other problems. It remains to be seen.

It could be medically useful, but, especially since the product and process is illegal, I don’t trust companies that try to do this [will create] a quality product that will be safe for consumers. I’m sure it won’t.

When something like this is done, it is not a 100% conversion. There will always be [possible contaminants and byproducts], and that’s a real trap, potentially. There can be nasty chemicals involved in the process that really have nothing to do with cannabis per se, but which are going to be very, very potentially harmful to the liver or other organs. …

[These chemicals] must be separated in the process, but God knows how strict the controls are in the manufacturing process. It doesn’t give someone like me confidence that everything will be done to a high security standard.

JH: What are your concerns about how THC-O Acetate is being used, especially with vaping?

ER: With cannabis concentrates there is great potential for a number of issues. The first is too high a dose, and it can happen all the time with garden strain THC. Many vape pens contain 70-90% THC. It goes beyond what everyone should need.

I know of a situation – someone in the cannabis industry who has been smoking cannabis for decades – who tried a vape pen for the first time and immediately passed out. I had what is called vasovagal syncope [a sudden drop in heart rate and blood pressure that leads to fainting] too high a dose of THC. So if we’re dealing with THC-O acetate, and it’s two or three times the potency, there’s great potential there. [for similar problems].

What happens when someone has too much THC? Well, that’s not pretty. A number of things: paranoia, anxiety. They can have what’s called toxic psychosis – basically it’s a kind of poisoning where you stray from reality for a while. In other words, you develop psychotic symptoms, delusions, hallucinations. It takes a few hours to go by, and you might end up in the ER with super strong sedatives to help bring you down. It doesn’t mean there will be permanent damage, but it’s not a picnic.

Another possible side effect is what I mentioned earlier, vasovagal syncope, where you pass out on your feet, fall to the ground, potentially break an arm, or have a fractured skull. This stuff happens. Also, when we are dealing with very powerful material and people do it over and over again, eventually they will develop a tolerance.

Now tolerance sounds like a pretty word. But in this case, it means that over time someone will need to achieve the desired level of elevation more and more. This development of tolerance is clearly associated with high potency vape pens, and the potential is even greater for a substance like THC-O acetate, if indeed two or three times the potency.

Under these conditions, this opens up the gamut of other possible side effects, including something called cannabis hyperemesis syndrome, where exposure to THC switches from the drug that helps relieve nausea and vomiting to one that produces nausea, vomiting, abdominal pain, etc. so on. This is a serious condition. We just published a newspaper article about it. Fortunately, this is not for everyone. It seems to have genetic susceptibility in some people.

There is still a potential for something called off-target effects, which means it might have another mechanism of action that regular THC doesn’t. … You don’t know until things have been properly tested. So, we know what it might do in terms of pharmacology similar to THC. But there is the potential for off-target effects, and it could be anything in any body system.

JH: Is there anything else you would like to say about THC-O Acetate, especially to hemp growers and processors?

ER: I would say don’t go there. Focus on producing a quality product, where you know what’s in it and it’s been made correctly — no pesticides, no heavy metals, all that good stuff — and forget about it. … find something else to do with your resources.

This interview has been edited for length and clarity.

Jolene Hansen is a freelance writer specializing in the hemp, cannabis and horticulture industries. Contact her at [email protected]


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