Beyond THC: Understanding the Full Therapeutic Potential of Cannabis
Part 1: Why High Potency THC might be backfiring.
Interview with Dr Ethan Russo
Read time: 5-6 mins
In the global discourse around medical cannabis, one critical misunderstanding persists - the belief that THC defines the pinnacle of the plant’s therapeutic potential. In this exclusive interview with Dr. Ethan Russo, a globally recognised neurologist, psychopharmacology researcher, and author, we unravel the science behind cannabis and why focusing solely on THC is limiting the potential of cannabis.
In Part 1 of this interview, Dr Ethan Russo joins The Insiders Extract, Adam Issac Miller, discussing how high-THC strains are often prioritised in both recreational and medical markets. How this is creating a cascade of side effects such as anxiety, dysphoria, and rumination, rather than the desired therapeutic or uplifting experience.
If you’re ready to move beyond the basics, this conversation is an essential read towards a more nuanced approach to cannabis prescription and consumption.
Adam Miller: So to begin, please, I would love you to explain why focusing solely on THC content is an incomplete picture of cannabis of cannabis's therapeutic potential.
Ethan Russo: I don't think many people have really had the experience of using THC as a pure compound. When they do, they're often quite surprised because it is very much the case that cannabis is not all about THC. It’s one major component. Over the last 60 years from its discovery, it's gotten the most attention. But it really is ignoring 149 other cannabinoids that the plant has made.
It's true to say we don't know that much about all of them. There are about 12 or 14 where we have at least some idea of the basic pharmacology, what they can do. But in each instance, it has shown that these other compounds have very many, often profound medical properties distinct from THC.
One example is we know that most of the cannabinoids that have been tested have activity against cancer cells but in each instance the mechanisms of action are distinct from one another and they certainly could act in concert. Rather than taking a cocktail of chemotherapy agents, we might be looking at a combination of different natural cannabinoids from the plant.
Going back to what I said initially, when THC is used as a pure compound, people will find it very disorienting, even dysphoric. Unlike cannabis, which often is described as producing euphoria, dysphoria is an unhappy sort of feeling. And that can be quite pronounced with pure THC. So even very experienced people using cannabis who try THC tend to say that they don't like the experience.
That's quite an interesting point. No one's ever articulated the side effect of dysphoria to me in that way before. So what you're saying is pure or high doseTHC actually can have a counterproductive output of dysphoria, which makes sense. And it's interesting how frequently I have heard of and experienced this myself with high THC.
In Australia, of the 2.5 million Australians who have consumed cannabis, per our 2023 Drug Household Survey data, about 80% of them roughly roll it in a joint. And then a further 23%, which is about 700,000 people, roll it with tobacco.
So my main point is with combustion, the temperature ranges from 600-900℃, where many of the minor cannabinoids and terpenoids are often degraded. You're basically getting THC, where the potency of the THC is quite pronounced when consumed via inhalation and specifically combustion.
From my observation, this can induce a sense of anxiety or, as you said dysphoria. And I've always been perplexed by that because when you do consume by inhalation with a vaporiser at a controlled temperature between 180-230℃, you can get this remarkable euphoric effect.
Part of it has to do with differences in what's delayed. So with a joint, as you mentioned, with the extremely high temperature, there's a lot of loss by the burning itself. But we're also in the side stream smoke. So, it certainly is the case that you can conserve more with vaporisation at an appropriate temperature.
Additionally, vaporisation, if the temperature is not too high, is going to deliver more of the terpenoids, which are going to provide the entourage effect and the modulation of the THC. Another issue, and I haven't looked at all the profiles, but it remains the case on most areas of the world that what's available is generally THC forward, or there may be specific chemovars that are cultivated for CBD content.
Most people, most places are not getting the full panoply of cannabinoids that might be available. And part of this is a byproduct of prohibition. When you've got a forbidden substance, you want the highest potency.
So during prohibition in the US, there was some beer made. But the standard drink was what was called bathtub gin, a distilled product. Since it's illegal you want to have it as strong as possible with the lowest volume and weight, and the same applies to cannabis now. So what we've seen is this elevation of THC content to the exclusion of other alternatives.
Additionally, we need better education because, again, it's a minority of people who understand the variety of experience that's available from this plant, exclusive of THC. So the average person goes into a dispensary in places that are legal and looks for the highest potency based on THC content.
I would maintain that they'd be better off looking for a specific experience. If there were someone there to guide them, by asking the questions: What do you mean to gain from using this product? What is your activity, or what is your desired state of mind? With the right preparation, those kinds of experiences can be enhanced.
Although, this seems to emphasise a so-called recreational market, but very much pertains to therapeutic use too, which should be more focused heretofore. For most people who are trying to treat something, it's a matter of what's available. Or if you're a company growing it, it's we have this stuff and maybe it's good for condition X. So we'll give it to a bunch of people and if they say they're better, we're there.
That really isn't focused on optimising the therapeutic effect. So this is something I've emphasised over my career, “Hey, sure, this works. But it could be a lot better…”
I like the idea of mood modulation, because obviously, there's the therapeutic modulation. Mood modulation is something that's not talked about very often.
From a health and wellness perspective, I would imagine that if you could gauge whether an individual is looking for a social experience, a relaxation experience, or a constant—like focused attention—and you could guarantee or at least have something that's close to the mark to modulate that mood state, that would be cannabis 3.0.
A way of really honing in on what people want and the intention of their consumption. But it doesn't seem that is a very common discussion point amongst the industry, the patients and consumers. Maybe just because of the lack of education, as you said.
Sure. And it's all based on intent. It doesn't take a lot of talent to produce a plant these days with north of 20% THC that can render its users extra galactic in short order. You know there's more to the experience to be had than rendering yourself immobilised and inside your own head. There are situations where somebody needs motivation to do a job that isn't so attractive, like cleaning the garage. Well with the right material, it could be less onerous or even fun. That is, I really appreciate what you just said there.
And I just want to pivot a moment. You just mentioned “in your own head.” Are you able to elaborate on the reasoning as to why strains north of 20% seem to have this uncanny effect of, we'll call it rumination?
Well, again, a lot of it has to do with the fact that these high-potency materials are deficient in a full complement of terpenoids, which, for better or worse, remains the case in most areas of the world. Most often available are high-myrcene products. The combination of myrcene and THC in high concentration is notorious for producing the phenomenon called couch lock. Which means just that, the person is immobilised and can't get up from the couch.
That's fine if you're the kind of person who has too much energy and is always going and needs this to relax, or if somebody wants to go to sleep. But again, that doesn't reflect the full capabilities or potential of the experience. So there's a lot more to be had than being couch-locked from your cannabis experience.
Then could you comment on why rumination is such a common occurrence?
Rumination is a passion point of mine; I've been caught in rumination cycles a number of times. A lot of people that I've met are averse to using cannabis because of that potential or previous experience of paranoia and internal rumination. Whether it's the way that people are looking at them or perhaps, overanalysing their own human experience. I get feedback that its quite a common phenomenon; that people overthink with certain high potency strains. I don't know if there's any potential reason for that?
I love that. Yes, I think I can offer my explanation, which is too much THC and too little of other substances that buffer the experience and render it better. I can tell you that we're doing a lot of formulation work. Part of what we do is trying to get the components that are going to be most therapeutic, knowing our mechanisms of action.
A lot of it is also increasing the so-called therapeutic index of THC. What that means is, how much can you use without having side effects? So, for example, 10mg of THC is going to be too much for most people, unless they have some degree of tolerance. And that's whether it's taken orally or inhaled or what have you.
It is possible, with a properly optimised preparation, that the 10 mg of THC doesn't produce the paranoia or the anxiety or the rumination, but rather that the person feels good and is having therapeutic benefit. So, this is quite different.
Additionally, we should mention that the cannabinoids tend to be associated with what is called a biphasic dose response. Let's break that down. In layman's terms, that means that they do different things at different doses. So, a very, very low concentration of THC will tend to be anti-anxiety, whereas too much, as you mentioned, certainly promotes anxiety. We can see a similar thing with the other cannabinoids, that you have to have things in the right range to get the desired effect. With high-potency material, it's very, very simple to overshoot and again, without tolerance, many people will find that one deep inhalation on a vape pen with enormous THC content is already too much.
What I have observed, there are a few ways to lead to panic with high THC. One of them is the physical sensation - if your body feels distressed. For me, and I know many others, it's often within the chest. And that observation of discomfort then creates an initial response, “What is going on?” And then that starts to generate rumination, “What's going on? Am I okay?” This is for less experienced individuals. If you know what you're in for, then you just know that you have to ride it.
But a lot of people, I think, either have an unfamiliar physiological discomfort, perhaps tachycardia or feel think they're having a panic attack, and it's associated with rumination - it's tricky territory. And that leads to the current discourse in Australia of psychosis and cannabis.
Again, too much THC. Often because just the overall amount or lack of other cannabinoids. Amazing that it's not classed as a psychedelic then Well, it can be... So, you know, a few years ago, a group in Italy described a related compound called THCP, tetrahydrocannabiphorol-4-ol.
This is like THC, but it has a 7-carbon side chain instead of 5. It has 33 times the potency of THC. So you understand that even a tiny amount of that could put somebody well into the range of feeling or acting crazy.
Most labs are not testing for it, but it could explain the occasional phenomenon of a chemovar that tests as seemingly having a moderate or low THC, but the effects are far beyond what people expect.
That is really interesting, and this is why I value this content! because it gets shared with doctors and prescribers. Sparking questions as to what is really being consumed here. Especially in Australia, where there's a lot of media slander right now around the plant, for a number of reasons.
It continues throughout the world. An important thing to emphasise is that it can be better, and it certainly will be better if there are legal and regulated markets. I think that bringing this out of the shadows, allowing people to engage in selective breeding without the threat of legal repercussions, opens up a great deal of possibilities. And certainly it's inarguable that there's a comparison between cannabis and alcohol. Alcohol is responsible for vast numbers of deaths and morbidity around the world.
Cannabis is a safer substance and it can be safer yet, if it's used properly and bred properly.
Dr. Ethan Russo is a board-certified neurologist and globally recognized authority on medicinal cannabis and the endocannabinoid system. As founder and CEO of CReDO Science LLC, he builds upon his previous work as Senior Medical Advisor at GW Pharmaceuticals, where he helped develop groundbreaking cannabis-derived medications including Sativex® and Epidiolex®. Dr. Russo's pioneering research on the "entourage effect" and clinical endocannabinoid deficiency has fundamentally transformed our understanding of cannabis therapeutics, while his extensive publication record—over 50 peer-reviewed articles and several influential books—has established him as a prominent bridge between conventional medicine and ethnobotanical traditions. Combining rigorous scientific methodology with deep respect for traditional plant medicines, he continues to advance the field of cannabinoid science through research, education, and advocacy.
Disclaimer: This information is shared with a global readership for educational purposes only and does not constitute medical or business advice. All patient-related information has been de-identified OR fictional to protect privacy. Nothing in this article is intended to promote the use or supply of medical cannabis to members of the public.
