How Terpenes Radically Change your Experience of Cannabis

Dr Ethan Russo Cannabis Terpenes

Dr. Ethan Russo a neurologist and psychopharmacology researcher. If you are in the cannabis industry or looking to be this episode will help you to understand the most important scientific aspects of the cannabis plant. Specifically, you will learn how terpenes radically change how you experience cannabis. Learn more about the benefits and science of cannabis terpenes.

Key Takeaways:
[1:00] – Dr. Ethan Russo’s background
[4:26] – Dr. Ethan’s study of cannabis
[6:15] – How does cannabis affect migraines
[8:35] – Dr. Ethan’s take on why cannabis was put on Earth
[9:38] – The endocannabinoid system
[12:44] – What is a receptor
[13:37] – Differences between indica and sativa
[17:56] – Dr. Ethan talks about the interplay between terpenes and cannabinoids
[24:11] – What does cannabis smoke do to the lungs
[27:01] – Rescue shots if you get “too high”
[28:31] – Dr. Ethan discusses the anti-inflammatory properties of cannabis
[30:50] – What does cannabis do to the human body
[37:18] – How does cannabis help with chemotherapy
[39:37] – Dr. Ethan talks about CBD
[41:10] – What is THCV
[43:43] – Dr. Ethan answers some personal development questions
[48:28] – Dr. Ethan Russo’s contact info

 

Important:
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Read Full Transcript

Matthew: We are going to look at the cannabis plants today with a different lens with Dr. Ethan Russo, a neurologist and psychopharmacology researcher. If you're in the cannabis industry or looking to be, this episode will help you to understand the most important scientific aspects of the cannabis plant. Dr. Russo, welcome to CannaInsider.

Dr. Russo: Thank you for having me.

Matthew: Give us a sense of geography where are you in the world today?

Dr. Russo: Well, I'm at my home, Vashon Island, near Seattle, Washington.

Matthew: Okay, quite an active cannabis community there, I know that. What's your background? How did you come to study plants and get into this industry?

Dr. Russo: Sure. Well, I'm a neurologist, and I had standard training, and pharmacology is any physician did, the difference was that as a teenager I had an interest in medicinal plants. There was a fellow named Euell Gibbons who wrote a book called "Stalking the Healthful Herbs," and I used that information to use something called Jewel weed to treat my poison ivy, which was quite successful. However, a lot of that tendency that I had fell by the wayside. If you forgive the expression, I was indoctrinated in standard pharmacology. But when I got out into practice in Montana, after I'd been there about seven years, it seemed to me that I was giving increasingly toxic drugs to my patients with less and less benefit, and I looked again towards medicinal plants as an alternative. Eventually, after spending sabbatical in the rain forest in Peru with the Machiguenga tribe, when I came back in 1996, I quickly became embroiled in the cannabis controversy. The benefit to me was that I found the topic really fascinating. And once I saw the incredible versatility of this agent to treat a wide variety of diseases, I was hooked, if you would, and everything went from there.

Matthew: Okay, so tell us some more what you're doing in Peru, down there.

Dr. Russo: Well, I was interested in looking at the medicinal plants that this particular tribe, the Machiguenga, used to treat migraine headaches. But as well, I was interested in any of the herbal agents that they utilized that were psychoactive. And as the case in most Amazonian tribes, there were many in both categories. I was a grad student who knew the language, and over the course of a couple of months, we documented 500 medicinal plants that they utilized, and that wasn't all of them by any means, but I was able to see firsthand how effective their medicines could be. It just opened up a world of possibilities for me in terms of additional research on looking for better ways to treat various human illnesses for which conventional medicine doesn't always have a lot of answers.

Matthew: Okay. Well, how did you even get connected with a tribe like that? What's the process?

Dr. Russo: Well, I was in touch with a large number of ethnobotanists, those are scientists that study medicinal plant use among indigenous peoples. And I came to know of the work of Glenn Shepard who was a grad student at Berkeley at the time and contacted him, and eventually, we decided to work together in Peru.

Matthew: Okay. And then, how did this evolve into your study of cannabis and understanding of cannabis?

Dr. Russo: Well, in 1996 when I returned to the States from the sabbatical, I remained very interested in medicinal plants, and particularly, those psychoactive ones, and developed a liaison with Rick Doblin at MAPS, the Multidisciplinary Association for Psychedelic Studies. So he also was interested in the same kinds of things, and very soon he proposed that I try to study cannabis and migraine, which is something I had been interested in, anyway. But at the time it was highly controversial as it has remained today, but at the time there really weren't any clinical studies of cannabis and humans going on. Of course, Donald Abramson, San Francisco, was trying to do studies in HIV/AIDS, eventually, was successful. In contrast, I never got permission from the federal government to do this. And by 1999, on my third try, I actually got the Food and Drug Administration to okay the study of cannabis and migraine, but then it was subject to other bureaucratic stalling through the National Institute on Drug Abuse, and I never received permission to do the studies. So it's been about 20 years that I've been trying to do the study in the States, and it still has never happened.

Matthew: Oh, gosh, frustrating, but not totally surprising. Well, as long as we're on the topic of migraines, how does cannabis affect migraines in your experience?

Dr. Russo: Well, interestingly, it has two totally different actions. If we look at the medicines that are used to treat a migraine, there are two categories, those that are used acutely to treat the symptoms and hopefully stop them, including the pain, the sensitivity of the eyes to light, the sensitivity to noise, and nausea. And then the other approach to treatment is a preventive one. So if someone has frequent, severe migraines, the idea of that kind of medicine is to give it daily and see if they can be prevented entirely or at least reduced in number and severity. Interestingly, historically, cannabis has been used in both situations, at the time to try and get rid of a headache and as a preventive. Usually, if we look at other medicines, so these are distinct things. You get medicine A is good acutely, medicine B is good as a preventive, but cannabis seems to have this multi-modal, a fact that makes it good for both types of treatment. So it's particularly interesting in that regard, right.

Matthew: Yeah, that is interesting. I mean, I'm sure there's a lot of people out there that are really interested in curing their migraines. I've only had one in my life and I just couldn't believe how bad it was. I was like, I finally understand people...when they're talking about migraines. It's totally debilitating.

Dr. Russo: This isn't nice, but I think that if more people had the experience just once, they'd be more empathetic with people that have this. Because as you found out at the time it can be totally debilitating. And if people are having a lot of these, it really puts some major cramp on lifestyle and enjoyment of life. There was a survey done some time ago that patients with a chronic migraine rated their quality of life worse than that of diabetics and people with other chronic diseases. So it really can ruin things.

Matthew: Zooming out to look at cannabis plant in a wider perspective, do you think the cannabis plant was put here on Earth evolutionarily to make us high?

Dr. Russo: No, I don't subscribe to that. You know, I guess, if in a solipsistic way, if people think that everything was put here for purpose of man, I think they're ignoring evolutionary history. Let me explain that, if I may. Humans are probably several hundred thousand years old as a species, whereas cannabis is about 60 million years old. So it was around a long time before there were humans to appreciate it, but presumably some of our forebearers, other species might have used it. There's evidence for chimpanzees seeking out certain plants to treat their parasites, so this seeking of medicine is not solely confined to humans.

Matthew: How do you explain the endocannabinoid system to somebody that's just learning about it?

Dr. Russo: Well, it's tough because education has been so lacking even for modern physicians. So with cannabis and it's controversial, and I suppose you could explain that when Dr. Stone knows anything about it is because of that controversy and its illegality, but let's look below that. One of the primary ways in which cannabis works is that THC, the main psychoactive ingredient of cannabis closely resembles natural chemical center bodies. These are called endogenous cannabinoids, cannabinoids within or endocannabinoids, same thing. So one, in particular, anandamide, the first discovered about 1990, very similar in its effects to THC. It lodges on this receptor called CB1, the psychoactive receptor in the brain. And as it turns out, that is really key to how our brains work in terms of all these other neurotransmitters, chemical messengers in the brain, because CB1 modulates how they work. I guess I could give one example. Glutamate is a stimulatory neurotransmitter, so it increases the signal through the nerve pathways. And that's good, it's important very definitely, but when there's too much of it actually produces something called neuropathic pain, nerve-based pain. CB1, in contrast, lowers the release of glutamate and treats neuropathic pain. Now, we could say the same thing about any other neurotransmitter in the brain. This endocannabinoid system affects the levels of all the neurotransmitters, and so it is important in pain, in emotion, whether you're gonna vomit or not, whether you're gonna have a seizure or not, almost any function you can name, and it's not just the brain.

The same thing applies to digestion where the endocannabinoid system is responsible for modulating propulsion, how fast things get through the gut, and secretion, how much water or lack of water there is. So if we look at any aspect of how our bodies work, our physiology, you've got some element of the endocannabinoid system that affects that. So it is a key modulator of what we call homeostasis, that's a natural balance in the body. When someone uses cannabis medicinally they are keying into these natural mechanisms which sometimes are deficient and need supplementation.

Matthew: Okay. Just so I can visualize what a receptor is, is that kind of like an outlet in a plug where there are a male and female, and the plug goes into the outlet in the tunnel receptor, binds...I mean, how could you describe that?

Dr. Russo: Yeah, it's a fairly good working model. Of course, because it's medicine it has to be a lot more complicated than that. But it can be thought of that way or like a lock and key. So we have the lock, which is the CB1 receptor, and the key in this instance can be a natural chemical called anandamide or it can be THC from the plant, both fit there on an act in a similar fashion. Then things get more complicated because there are other things that change the way the lock is and how tightly things bind, and so you can start off with the basic concept and make it a lot more complicated, and that's how it is in the body.

Matthew: Is there a real difference between into Indica and Sativa?

Dr. Russo: Well, we've hit one of my pet peeves, but let me explain. So the term Cannabis sativa means cultivated cannabis, and it was described in the 16th century by somebody called Leonhart Fuchs in Germany. And then Linnaeus, the famous botanist who gave us our binomial nomenclature, two names for a species, also called a Cannabis sativa. A short time later, and this is now in the 18th century, Antoine Lamarck describes something else. This is called Cannabis indica. But what he described was a plant from India that had narrow leaflets, it was a little different, he thought this Cannabis sativa that was growing in Europe, which we would recognize as hemp.

But there was never agreement on this, it was recognized that these two entities, let's call them, could interbreed, and I'm afraid that you don't get a lot of uniformity of opinion by botanical taxonomists. Those are the people that decide whether it's this species or that species. Let's fast forward to the 1970s. One of my mentors, Richard Evan Schultes at Harvard, went to Afghanistan when he could still do that. He saw that they had these short bushy plants in Afghanistan that he called indica. But you know what? It really didn't look like the Cannabis indica that Lamarck was describing. It seemed to be different yet. However, in the intervening decades, we've developed this common parlance of Sativa and indica, and the methodology is that Sativas are innovating up head high, whereas Indicas are sedating in a body high. And this is based somehow on what the plant looks like, and it's the shape of its leaflets and all, but it's very unreliable kind of formulation.

What we really need to know is what are the biochemical contents of the cannabis that produce the effects that someone either wants or doesn't want? And so I prefer to talk about what we call chemovars, chemical varieties. And to describe those, you need to know what the contents are, what the content is of THC, tetrahydrocannabinol, what the content is of CBD, cannabidiol, which has very different effects, and also another set of chemicals called the terpenoids. These are the aromatic compounds in cannabis that are also found in other plants like pine needles and citrus rinds. But those chemicals modulate how THC and the other cannabinoids work. So, if we really are interested in how this is going to affect a patient or someone who's using it recreationally, you have to know the chemical contents and you can't know that from descriptions like Sativa or indica. Besides, the breeding is so complicated. I'm afraid that these labels, as they're commonly used, just don't help the potential consumer at all.

Matthew: Well, you've mentioned something there and I wanted to dive into that. Can you talk about the interplay between terpenes and cannabinoids more? For example, you're saying, like if you took a terpene like a myrcene or pinene, or something like that you could...and you intermix it with your cannabis or add it to your cannabis or adjust the quantities, it changes how that cannabis affects you, the same cannabis, with more or less or different terpenes. Is that what you're saying?

Dr. Russo: Right. So, well, the easiest way to look at this is, we know a lot about THC, the main psychoactive chemical in cannabis. In 1985, synthetic THC was approved by the FDA as a standalone drug called Marinol. But, very quickly, patients notice that gee, you know, THC isn't like cannabis. When people took this, even if they were cannabis experienced, they found that THC tended to make them confused, there was this flight of ideas that made them unhappy rather than euphoric, and it was really hard to handle. Something was different, something was missing, and the something that was missing was other cannabinoids like CBD that limits side effects of THC, and the terpenoids weren't there at all. The terpenoids also modulate, change the effects of THC.

So let's give a couple of examples if we can. You mentioned myrcene. Myrcene is far and away the most common terpenoid found in modern North American types of cannabis. Let me mention, I don't call them strains, strains of bacteria. Again, we prefer the term chemovars, chemical varieties. But myrcene is prevalent, extremely prevalent in the offerings that people get in the dispensaries these days. It, on its own, is mildly sedating, but when you combine it with THC, it becomes extremely sedating and produces a phenomenon commonly known as couch lock, which I think is a very evocative term. It means, basically, you're immobilized. Well, you know what? If somebody is injured and they need to sleep, that's a good thing and some people like that effect. But if we have a patient who needs to work or study, this really isn't gonna be helpful to them. What they need to do is to be able to function.

Now, another side effect of THC, of course, for which it's notorious is the short-term memory loss. This is where...and this is classically portrayed on "Cheech and Chong" or any movie about cannabis where people laugh because they can't remember. They lose their train of thought. Yeah, so that's amusing, but it's not helpful if you have to concentrate on something. And this should be particularly the case for a patient who has to function in their daily life, you know, they have to take care of their family, or they have to work or they have to study. So what can be done about that? Well, there is another terpenoid called pinene. It's in pine needles, of course. This counteracts the short-term memory impairment that THC produces. So if in contrast to the excess of myrcene, there is a chemovar of cannabis that has a good amount of pinene, there is the likelihood that the person can gain their symptom control, control of pain, or whatever else the problem is, and still be able to function.

Right. And I mentioned that THC alone produces dysphoria, unhappiness. That can be changed if there happens to be limonene, another terpenoid in the cannabis. Limonene is a very powerful immune stimulant and antidepressant. It makes the cannabis experience sunnier, if you will, marked improvement on mood. And this should be familiar to anybody even if they haven't used cannabis. Because if you walk down the detergent aisle in the supermarket, what do you smell? Lemons. And there's a reason for that. Because psychologically this citrus scent is evocative in our brains of cleanliness or happiness. So, it's a bit of unsubtle advertising, but it also is a very powerful cleaning agent. So there's a reason for this. We're being subtly or unsubtly programmed.

Matthew: Yeah, I can see, where if I owned a casino I might be, you know, letting loose some limonene in there, I'm just kidding. But how about for the...if someone were to walk through a pine forest or something like that, could they get the same benefit from this terpene, from the...

Dr. Russo: To a certain extent, yeah. No, I am glad you mentioned that because this communing with nature is a feast of the senses, it's the sight and smells, and maybe birdsong, but let's concentrate on the smell. When you go particularly in the northwest where I live, if you go into a coniferous forest, the primary odor there is gonna be one of pinene. And it is this reversal of the short-term memory loss, also works on a normal brain without cannabis. So there's been an alerting effect because what it's doing is increasing the amount of the acetylcholine in the brain. It's inhibiting its breakdown, and acetylcholine is the memory molecule. In fact, in Japan, they have a term for this. It's called "shinrin-yoku," which means forest bathing. And this is why in a busy city like Tokyo, you'll see nests of forests and gardens where people can go and refresh their minds from the busy lives.

Matthew: That's a great idea. Yeah, they do seem to have this idea of balance in nature in Asia much more thought out. Let's pivot to what cannabis smoke does to the lungs. Can you tell us about that?

Dr. Russo: Yeah, I'm afraid I have to emphasize I'm not a proponent of smoking. Smoking anything is irritative to the lungs. It's simply inarguable at this point that smoking is a good motive administration. Because even when people need it, smoking of cannabis produces cough, phlegm, and bronchitic symptoms. Now, on the plus side if it's just cannabis without tobacco, we have no evidence that that produces lung cancer. However, it still does produce potentially carcinogenic molecules that the body has to process.

So it is not the best mode of administration. Beyond those side effects, it also, because of how quickly it works, there's a quick onset and offset. So if someone is smoking to treat their condition, they'll likely need to do it many times throughout the day, because the peak effects are only gonna be for one to three hours. For a chronic condition, it's much preferable to use an oral form of administration or perhaps a tincture in the mouth, it's gonna last a lot longer, it's not gonna produce these peaks of activity that can lead to more side effects. So that's better. And I should mention vaporization. Vaporization is inhalation of cannabis without actually burning it. So there are fewer of these poly-aromatic hydrocarbons, the potential carcinogens, but nobody's really demonstrated that they're totally eliminated yet, so it's unlikely, for example, that the Food and Drug Administration would approve vaporization as a method of applying prescription to forms of cannabis unless the technology improves a great deal. They also don't like the fact that there is again this quick peak of cycle activity. They prefer something that is going to produce symptom control without producing a high or other side effects like anxiety that are prone to occur if someone gets too much THC too fast.

Matthew: Right. I noticed some rescue type of shots and things that come on the market. I mean, you may not have had a chance to look at those yet, where they say, "Too high, take this shot of such and such, such and such." Would that have some of these terpenes in there? Would you conjecture?

Dr. Russo: Yeah, may will. Some years ago I wrote an article in "British Journal of Pharmacology" called "Taming THC." And one of the aspects of that was to look at what had been suggested historically as antidotes to cannabis overdose, if you will, and I should mention here, overdose here doesn't mean that you quit breathing, that can't occur with cannabis, but rather being too high, becoming paranoid, or anxious. But what we see is a couple of things we've mentioned already. Lemon juice was one presumably because of limonene content, and pine nuts which have pinene in them was another. So I can't endorse any of these products.

Additionally, I don't know what is in any particular one. There is a concept behind them though. What I think might be better is to have chemovars cannabis that have this built-in safety margin because they contain the right amounts of those components like the terpenoids that are going to reduce THC-associated side effects.

Matthew: Yeah. Gosh, this is such a fascinating subject, it really is. But let's move on to the anti-inflammatory properties of cannabis. Can you tell us about that?

Dr. Russo: Sure. Well, there are so many. TT has some affects this way. Where cannabis really shines as if it's got cannabidiol in it as well. Cannabidiol was pretty much eliminated from North American recreational cannabis over the last several decades at least until recently when their interest developed because it became known that cannabidiol was good in treating seizures, epilepsy, and many other conditions. So cannabidiol is psychoactive, it reduces anxiety, and reduces paranoia, but it doesn't make people high. So it has no abuse potential, but additionally, it is what's called an anti-inflammatory analgesic, meaning that it reduces inflammation and pain, and without producing a high or addictive potential.

Additionally, there are many, many other components of cannabis among the terpenoids that also are anti-inflammatory and may affect pain, to reduce it. So, really, what we're dealing with in cannabis is a multi-modality synergistic agent. In other words, it works through different mechanisms. Synergy is a boosting of the effect. So instead of two plus two equals four, this component plus that component in cannabis might be equal six.

Matthew: There are so many conditions that could benefit from the anti-inflammatory properties. I mean, I know friends and family members that have rheumatoid arthritis, they have psoriasis. There's just an endless amount...not endless, but there's a lot of people suffering from problems of inflammation, or at least that's a side effect of some sort of problem they're having in their body. So I think there's huge promise here and probably not even talked about enough, but let's move on. What does cannabis do to the human body when it's consumed?

Dr. Russo: Well, it depends a lot on the dosage and the method of administration. Let's look at smoking which remains the most prevalent type of activity. There, what is happening is people inhale the smoke or the vapor, it's rapidly taken up by the lungs, into the bloodstream, and gets to the brain. And there, among other things, it's stimulating the CB1 receptor, that affects neurotransmitter levels. If done properly, the person will tend to relax. They may, if it's not too high a dose, it will lower anxiety. If it's too much, they might have trouble remembering their train of thought, on and on. When taken orally, the absorption is going to be slower on...there'll be fewer of these peak effects or they may just be delayed somewhat.

But, really it's a matter of what's in the material because cannabis isn't just one thing, it is a neuronal agent with a lot of potential ingredients and different proportions. And this is why I have been such a proponent of the idea that consumers really need to know what is in the material. It's analogous to the difference between somebody that goes to the grocery store and just pile things in the cart and doesn't pay a lot of attention. As opposed to the person that looks at every label to ensure that radiance to which they're sensitive or that kind of thing, I'd like to see consumers be as exacting in their requirements when they go to purchase cannabis.

Now, unfortunately, we need the help of governments to regulate this. Because as it is now at best, even in states where it's legally accessible, generally speaking, the most somebody is gonna get is a listing of how much THC it has and how much CBD it has. Rarely if ever will the consumer have access to information on the terpenoid content or actual objective evidence of what other consumers have reported in relation to this. So then people have to rely on what the bud tender tells them about it, and again, they may be experienced and know what they're talking about or they may not really know. So it's a difficult situation, and again, produces this difficult intersection between what the consumer might want and what the law allows.

Matthew: Yeah, it would be great if a trade group, or some group of growers, or some leaders in the industry could come up with the standards on their own and say, "Hey, look at our best practice as the cannabis cultivators of California that we're gonna provide this on all our products sold at dispensaries." That'll be wonderful.

Dr. Russo: Sure.

Matthew: But I mean, I can see a day where, you know, you get some product at a dispensary and it shows you the cannabinoid profile, the terpene profile, so you can get a sense. Like, let's say someone tends to be a little bit more paranoid than they like from consuming flour and they know like, "Hey, compared to my friends, I'm just a little bit more paranoid." You're saying in that situation they could just maybe look for some flour or some infused product that is high in a specific terpene that could then get them much closer to the sweet spot for them?

Dr. Russo: Right, exactly, and the best dispensaries actually have this capability. I've been to ones where there's a binder, and you can see just that, a graphic depiction of total cannabinoids, cannabinoid balance of what the various terpenoid levels are and what patients have reported when they use it in terms of being more relaxed, being more mentally active, whatever it is. And people can look at that and say, you know, "I'd like to try this one," or similarly, you could tell the bud tender, "Well, you know, I'm looking for this effect, but I don't want that side effect on..." Again, between them they could come to a mutual decision as to what to try. But again, this isn't legally mandated anywhere, and it applies also the safety issue.

If I could use my home, Washington State, as an example, you know, legalization here hasn't been particularly great to the medical consumer. There was a good market before where people had availability of reportedly organically grown material that was working for them, and there were liberal allowance limits on what someone could possess. Unfortunately, the medical market was mandated to be folded into the recreational markets, and so a lot of the chemovars that people would use medicinally were no longer available. There were limitations on what they could get, certainly limitations on the information available, and on the safety side there was no requirement made for testing of pesticides. And we know from studies that we did last year that there has been rampant pesticide contamination in the legal cannabis market in Washington State.

Matthew: Oh yeah, not just Washington State, it's everywhere. It's systemic, unfortunately.

Dr. Russo: Right.

Matthew: Now, how can cannabis help people going through chemotherapy?

Dr. Russo: Well, a couple of ways. The most obvious is in allaying nausea and vomiting. This has been known, again, for decades on...it was the reason that synthetic THC was approved by the FDA for that indication in 1985. And people will say, "Oh, the studies are old and we have better medicines now." And that's true to some extent, you have what are called serotonin type 3 antagonists, the drugs ondansetron and granisetron. Those work for a lot of people, but they don't work on a special kind of problem in chemotherapy called anticipatory nausea. And this is sort of a condition reaction where someone will get nauseated when they walk into the chemotherapy suite before they've been given anything. Actually, the cannabinoids work quite well for that, and we know from thousands of patients who have failed traditional agents to treat nausea associated with chemotherapy that cannabis often works beautifully for them.

So that's the one big thing. But I really need to mention also how cannabis seems to help people's adjustment to a very difficult chronic condition like cancer and just lets them cope better because it's not just dealing with nausea. Almost invariably these are people in pain, either from the cancer itself or side effects of chemotherapy. So there's that, and there's the disruption of their sleep, cannabis is gonna help with that. And then, again, just this emotional factor, the ability to separate themselves a little bit from the situation, to laugh at the irony of the situation, just overall adjust to this challenge to their life.

Matthew: Sure, great points. I want to circle back to CBD for a moment. You say that CBD is not potent, can you specify what you mean by that exactly?

Dr. Russo: Yeah, well, you know, we're Americans, we're hung up on having the most bang for the buck. So potency, with respect to a drug, means that a lower dose gives you the effect that you want. So THC is relatively potent. If you look at the numbers, the milligram somebody needs a day, it's usually very low. In contrast, cannabidiol, you need higher amounts. Part of this is because it isn't always absorbed well if taken orally. It needs a good carrier, like a fat. But beyond that, the numbers that you need to control seizures, for example, can be a lot higher than for THC. So that's all it means. Potency isn't an issue unless something is really expensive. So, you know, if you're growing medicine and there's enough CBD, the fact that you need a higher number isn't a bad thing because CBD is so non-toxic that you can take hundreds and hundreds of milligrams without producing any serious side effects. You know, often a combination is better. So, for many, many conditions a touch of THC, a very little amount with a much higher number of milligrams of CBD may be the best approach oftentimes.

Matthew: What is THCV, and what's important to know about that?

Dr. Russo: Yeah, well, that one is a little bit inaccessible in current offerings in cannabis in North America. So THCV stands for tetrahydrocannabivarin. It is quite similar in appearance to THC except it's got a three-carbon side chain instead of five. Now, THCV is present in small amounts in some cannabis chemovars from southern Africa, so South Africa, Zimbabwe, Lesotho, that area. It is a really interesting molecule. It's got some similarities and some distinctions from THC. So THCV at low doses actually is what's called a neutral antagonist at the CB1 receptor. So it actually reduces hunger rather than producing it. At really high doses, it acts more like THC so it changes its pattern. THCV is interesting medicinally on a couple a lot of levels. On the one hand it reduces hunger, it could produce weight loss, it also improves lab values in diabetic people in what's called the metabolic syndrome. So this could be very useful to people who have an obesity problem or pre-diabetic. But beyond that, it also is a very useful drug for treating nerve-based pain, neuropathic pain, and as an anti-convulsant for seizures. As it is now, most cannabis varieties have very, very small amounts of this in North America. GW Pharmaceuticals in England does have a plant where 92% of the cannabinoids that it makes are THCV, and so they do have this in early clinical trials for some of the situations that we mentioned.

Matthew: Gosh, there's so much still to learn here. I feel like we're just at the dawn of a huge, huge wave of knowledge that's just kind of gonna settle upon us, and there's so many different directions I could take this interview, but it's time to draw to a close, and with that I just wanna ask you a few personal development questions before we go. Is there a book that has had a big impact on your life that you'd like to share with listeners? It doesn't have to be about cannabis, or anything, or science, but just anything in general?

Dr. Russo: Well, you know, Matt, it's a surprisingly tough question for me because I read a lot and I've had so many influences. Would it be okay if I mention two? Well, I was very influenced when I was about 18 on the works of Herman Hesse, and I'd it single out" Siddartha" as a knowledge of discovery on opening the mind to different possibilities. So that was very influential to me as were his other writings. On the non-fiction side, I again cite one of my mentors, Richard Evan Schultes, the ethnobotanist. And again, when I got back into the study of medicinal plants, his books were my Bible for developing leads on where we should look. And I would just emphasize that one of the failings of humans is to understand the lessons of history. Just because something is old knowledge doesn't mean that it doesn't have applicability today, and that certainly is the case with respect to cannabis therapeutics. There are many old lessons out there that we need to heed once more or we're just gonna be wasting energy, where we have the evidence already and just need to follow up so that we can prove these things using modern techniques.

Matthew: Is there a tool, web-based or otherwise, that you consider vital to your productivity? Okay, can we pick up that call and ask that person what they're doing just for fun? We can turn this into a quick kind of like...

Dr. Russo: It's probably for my wife so I don't...

Matthew: That would be nice, too. Don't worry about that, it happens. Back to the tool, is there a tool, web-based or otherwise, you consider vital to your day-to-day...?

Dr. Russo: Yeah, I'm gonna mention two, one old, one new. Because I do a lot of writing journal articles and the like, a tool that's been essential to me is one called EndNote, and anybody who does a lot of writing that they have to reference absolutely has to have the software. So here's a learning curve to it, but once you input your reference you can be writing for any journal, and as long as you know the format, it will automatically put the reference in. You know, I do a lot of journals where they have a numbering system, and if you change one you have to change everything, and it's a nightmare to do this manually. But this just automates the whole thing, and there's something like 8,000 references I have put into this software now, and I just find it essential.

The second is just new to me in the last week. I saw a local news story on this in Seattle. Paul Allen has a Research Foundation at the University of Washington, and they've come up with a new search tool. It's called semanticscholar.com, I believe it is, or it might be .org, Semantic Scholar. So it's like PubMed in that you put search terms in and it gives you a list of references. However, it differs from the National Library of Medicine PubMed in that it really increases the pertinence level of each of the entries. And if there is a PDF online source for the article, it gives it to you right there. So it can save a tremendous amount of time in accessing articles on a given subject. I've played with it in the last week and I've been really pleased with how well it works.

Matthew: That's cool. I assume since you live in Seattle and Paul Allen was the co-founder of Microsoft, we're talking about that Paul Allen?

Dr. Russo: It is one and the same.

Matthew: Okay, he also created the...what, like a Jimi Hendrix Museum out there in Seattle? Have you've been to that?

Dr. Russo: Yeah. Well, you know, some people get money, some are frivolous with it, some manage to do good things.

Matthew: Yeah, he's done a lot of interesting things, I will say.

Dr. Russo: You bet.

Matthew: Well, Dr. Russo, thanks so much for coming on the show today. Let listeners know how they can, you know, find the articles you write and the different things you do, and just stay in touch with you.

Dr. Russo: Well, back to what we just discussed. If people put Ethan Russo and cannabis into Semantic Scholar, they're gonna find access directly to a lot of my articles, and that's probably the very easiest way.

Matthew: Okay, I really had a fun time today. You did a lot of educating around terpenes and some other subjects I just found fascinating. I wish this could go on for another hour, but alas, we have to close. Thanks so much for coming on the show today, we really appreciate it.

Dr. Russo: My pleasure.