How Does CBD Work? An Interview with Dr. Ethan Russo
How does CBD work? Is CBD safe? Am I going to get high taking CBD? Is CBD habit-forming?
More and more people are looking for ways to feel better naturally and are increasingly turning to CBD and CBG solutions. With so many options online, and at the grocery store and dispensaries, it’s hard to know what to look for in a CBD solution.
While many people have questions, they aren’t sure where to find the answers. Grocery stores, dispensaries and online stores sometimes offer conflicting answers or confusing information, as many of the terms used are new to consumers.
It’s common to turn seek answers from and insights about cannabis from healthcare practitioners, but these trusted sources may not be familiar with CBD, or lesser known cannabinoids like CBG and CBN, and may not be able to offer answers.
To get the answers to some of the most common questions people express about cannabis and CBD, Daygold’s Co-founder Liz FitzGerald traveled from Portland, Oregon to Vashon Island, Washington, to interview cannabis medical expert, Dr. Ethan Russo.
Dr. Russo is one of the most well-respected people within the cannabis industry. He is a board-certified neurologist and has been researching the medicinal benefits of plants, including cannabis, for 30 years.
In this interview, Dr. Russo provides an easy-to-understand description of:
- the endocannabinoid system (ECS)
- what to look for in CBD products
- the importance of testing
- how he formulated Daygold based on research
- the entourage effect
- how to get the benefits of THC without intoxication
We hope this interview answers your questions about CBD. Feel free to reach out to us directly if you have more questions at email@example.com.
Either watch the video, above, or read the full transcript, below:
CBD explained by a medical expert
Liz: As CBD becomes increasingly popular, people are looking for trusted sources of information and many are turning to their healthcare practitioner for those answers. In turn, many healthcare practitioners are also looking for trusted sources of information. Which is why I’m so excited to be here today with Dr. Ethan Russo, board-certified neurologist and esteemed plant researcher.
Thanks for taking the time to talk with me today.
Dr. Russo: Pleasure to join you.
Liz: So if we could start with providing a little bit of context about who you are. Within the cannabis industry you’re very well known and I’m not going too far on a limb to say you’re somewhat of a rockstar in the cannabis industry. But for people outside of the industry, if you could provide a little bit of an idea of your expertise and your experience.
Dr. Russo: Sure. Well I’m a board-certified child and adult neurologist and I was in practice for 20 years in Missoula, Montana, but along the way I rekindled an interest in medicinal plants and so it’s something I’ve been studying intensively for 30 years and that includes 25 years working on cannabis in the endocannabinoid system. I was involved in the development of two cannabis-based pharmaceuticals from GW pharmaceuticals: Sativax® and Epidiolex®.
Since March 2020, about the same time the pandemic started, I’ve been the founder and CEO of Credo Science which is a company basically devoted to bringing into commerce cannabis-based preparations and diagnostics and things of this sort.
Liz: Lovely, well thank you for that. You touch on a couple of things. I think healthcare practitioners may be familiar with the endocannabinoid system, also referred to as the ECS, but surprisingly it’s not really taught in a lot of medical schools and if it is it’s only briefly. Could you quickly explain what the endocannabinoid system is?
Dr. Russo: Sure. The endocannabinoid system is sort of the governing body for how our bodies work. It is what I like to call in technical parlance the homeostatic regulator of human physiology. Let’s break that down.
Homeostasis is a balance that a system is neither too active or under active. So bringing things back into a balance where they’re working in top-notch form and this would apply to anything neurotransmitter functions in the brain, digestion, you name it.
The endocannabinoid system is there to try and and maintain that balance. How this came to be discovered is that we have chemicals within, endogenous or endocannabinoids, that closely resemble what THC does in small amounts. So that’s how we learned about this. The real scientific advances began about 30 years ago.
Unfortunately though despite the importance of the endocannabinoid system, as you mentioned, it’s not commonly taught in medical school which is really a terrible deficiency and something we’re trying to remedy.
Liz: I was really just thrilled to learn about the endocannabinoid system. I love the fact that, as you mentioned, our bodies naturally are creating these endocannabinoids and that we have these receptors that then allow us to also receive phytocannabinoids from cannabis and so it’s just a really interesting way of understanding how our bodies receive this plant.
Dr. Russo: Sure. You know and especially one of the theories that we’ve been working on is that some people have deficient endocannabinoid function, what I’ve called clinical endocannabinoid deficiency. This predisposes people to a lot of problems which commonly would include pain conditions, difficulty sleeping, problems with digestion and you name it. It’s just a long list and this helps explain why cannabis is so versatile for so many different conditions.
One way of looking at it would be when someone uses a cannabis-based they’re trying to replace what nature might not be providing in sufficient amounts at the moment.
Liz: Yeah, I really like considering that as I’m taking my CBD, taking Daygold, I’m really thinking about the fact that I’m putting something into my system that my body very clearly recognizes, as it produces many of these things on its own.
Dr. Russo: Sure, yeah.
Liz: So, you are really well known for popularizing the entourage effect. It’s not a term that you came up with but it is one that really captured your attention, if I’m not mistaken, and that you’ve really, as I said, popularized it. Could you quickly describe what the entourage effect is and why it’s so important to consider this in any CBD product?
Dr. Russo: Sure. Well, this concept entourage effect was defined in 1998 by Professor Mechoulam and Ben-Shabat. Professor Mechoulam was the discoverer of THC way back in 1964. He’s 91 this month and still active, so he’s a model for all of us.
In any event, what he described as the entourage effect was the idea that there are two main endocannabinoids called the anandamide and two closely-related molecules which on their own that don’t seem to do a lot but when combined with the main players produce very marked effects—what we call a synergy or boosting of effect.
So they named this phenomenon the entourage effect. The next year, the same concept could apply at least theoretically to a drug like cannabis because some plants are better medicines than the chemicals derived from them.
That really resonated with me at the time and a good part of my focus since has been on how other components combine with THC and CBD to make it a more complete, better, safer medicine.
Liz: And is that what research has really shown you? That when you have this mix of THC and other cannabinoids—like CBD or lesser known CBG, CBN—with terpenes, that it really does boost the effect?
Dr. Russo: Oh I’m a firm believer. I was before but truthfully there have been many studies that support the concept of the entourage effect as applied to cannabis in the intervening 22 years. Now it’s also true to say that there are critics. Most pharmacologists are used to the idea of one medicine, one molecule, usually synthetic, with one target in mind. That isn’t reality, however. Any drug that you produce is going to have (hopefully) intended effects but also off-target effects often manifested as side effects.
The whole idea of an entourage is to combine ingredients that are going to enhance the therapeutic effect desired but at the same time reduce attendant side effects because THC on its own is a really difficult medicine.
There has been a synthetic THC on the market, FDA approved since 1985. However, that hasn’t had much uptake by the public because very few people tolerate it on its own. THC is sort of a beast that needs to be tamed and we can provide that with cannabidiol. Certainly some of the terpenes just calm it down a bit so that you can take enough to do what is needed in terms of treating symptoms.
Liz: Speaking of THC, some CBD formulas don’t have any THC in them. Daygold, which I’m the co-founder of and you’re the formulator of, does have between a trace amount and up to just under 0.3 percent so it’s considered hemp. But we do have THC in our blends and it’s something that we tout as very beneficial. Again, it speaks to the fact that there’s enough THC in there that you don’t get high and you don’t feel the intoxicating effects from that beast but you do still have those benefits. Because the research, it sounds like, has shown that a little bit [of THC] can really help to boost what the cannabidiol and other…
Dr. Russo: Absolutely. I’ve been a critic of so-called CBD isolates. So an isolate would be a preparation where most often the company has extracted the cannabidiol from hemp refuse. In other words stems, stalks, leaves and the like, and chemically they’ve just derived the CBD but on its own CBD is not what it could be. It’s a very versatile medicine, it’s not very potent, however. Certainly, on its own we see the necessity oftentimes to take very high doses which makes it expensive and inaccessible. In contrast, when CBD is combined with other components you can use a lot less and it can be more effective.
I’m fond of saying that there’s nothing that CBD does that isn’t enhanced by having just a little bit of THC and so, certainly, I was really pleased to have the opportunity in formulating the Daygold products. To have the ability to use that small amount of THC.
Liz: And so with the terpenes that is definitely something that makes Daygold very unique. In terms of all the offerings that are out there we’re the only product that has a dozen terpenes in each of our blends. So if you wouldn’t mind—I know you you prefer the term terpenoid—if you wouldn’t mind defining what is a terpene and then speaking a little bit to how you chose these different terpenes for our three different blends.
Dr. Russo: Okay, sure. First, definitions: terpenes are hydrocarbons meaning they’re molecules that have a hydrogen and a carbon and they can be 10, 15, 20 or 30 carbons and they have different names according to that.
Terpenoids have oxygen and rarely other molecules in them as well so all terpenes are terpenoids but not all terpenoids are terpenes.
Also I like the symmetry of the names of cannabinoids and terpenoids but the names are really used synonymously by most people.
Alright, next the more important question how did we come up with these combinations? Well, I had a system I’m a little hesitant to release this to the public but here we go:
I knew from a generation of study a lot about essential oils which is the source of most terpenes and terpenoids, so already we had targets in mind. I wanted to use materials that were naturally present in at least some chemovars, chemical varieties of cannabis, so that was number one.
Number two, I turned to aromatherapy practitioners. These are people that use essential oils for therapeutic purposes and I looked at if we had anxiety—as an example—what kinds of essential oils were typically used by experienced aromatherapists to treat anxiety, and you get a list and then you see what are the common components. What are the terpenoids in the essential oils? Most often you’re going to see linalool which is the main ingredient in lavender well known as a great agent for treating anxiety but then there are others. Some others are mood enhancers like limonene that have a little antidepressant effect and then you see others where maybe it’s not as clear but they keep showing up in the essential oils that seem to be good for that particular problem, so often we included those.
And then there was a culling procedure too. I didn’t want anything that would have a remote chance of toxicity and toxicity can come about because of a particular problem with the molecule or that you’re using too much but we wanted to keep that in mind.
For example, very rarely there is a terpenoid called pulegone that has been found in cannabis although I haven’t seen it in an analysis for about 20 years. High amounts of that that comes from pennyroyal has been associated with miscarriage so certainly we didn’t want that.
So that was it basically—trying to provide a rational formula based on which ones do we know are helpful in this situation, which ones appear in essential oils that are used for this problem, and then making sure that everything is going to be safe.
Also with an idea of what agents are going to counteract the small amount of THC. [For example] we know that too much THC can provoke anxiety. A little bit is good, too much provokes it and so again taming THC is part of the mission.
Liz: I love that. You’re a scientist but for the lay person I often define terpenes as the aromatic oils that are in thousands of plants.
Dr. Russo: Exactly. It could be the flower or sap or leaves depending on the species. For example, with citrus. Everybody knows the smell of limonene from lemon rind or orange rind but there’s some of the same components in the leaves. So depending on the plant involved it could be different plant parts but what they have in common is, as you mentioned, the aromatic components.
The plants use these for defense or sometimes to attract good insects but the lucky accident of nature is these things that help the plant cope with its environmental stressors also are therapeutic for people.
Liz: Yeah, plants are our friends.
Dr. Russo: Should be.
Liz: So when we’re thinking about terpenes, for Daygold we’ve derived the terpenes from botanical sources as you mentioned. I asked some practitioners for questions and one said, well, would you ask is there a difference, understanding that there isn’t molecularly a difference between a cannabis derived terpene versus a botanical? Can you speak to that?
Dr. Russo: There have been 200 different terpenoids that have been found in cannabis one place or another—none so far unique to cannabis, but in the best of all possible worlds it’d be great if we had a plant for each formulation that had exactly the components we wanted.
I’d love for that to be the case but it’s not right now. It might take 10 years of selective breeding to get there. In the absence of that the approach taken has been again a really rational one and scientifically justifiable because we’re using botanicals with meaning plant-based components with known effects and also an effort was made to make sure that they had the right confirmation.
This is where it gets complicated. Plants have three-dimensional structure. Some are left-handed. Some are right-handed. The left-handed and right-handed molecules can act differently. They may have slightly different odors and slightly different effects. We wanted to have that for these blends and I believe that’s been achieved.
Liz: So that sort of speaks to these ratios that each Daygold blend has a certain amount of cannabinoids and as I mentioned CBD and CBG. Then in Restful Night we also have a little bit of CBN and then this mix a different amount of THC and then the blend of terpenes. So with that ratio again I guess you sort of answered that, but how you came to decide this is the ratio that I’d like to have for these.
Dr. Russo: Sure. With the cannabinoids it’s pretty easy. The rate limiting factor is usually THC, enough to do the job not too much to create side effects. Truth be told with the sleep formula we had to adjust downward. We started with an amount we thought most people would tolerate but there were a few people, and this happens, where THC activates them they can’t sleep because their mind is going too fast. For some people they even get eyelid movies if the dose is too high so we cut that in half and then the product seemed to work quite well in people who tried it.
Then with CBD, recognizing again that it’s just not as potent as some of the other cannabinoids, and so you need a certain number. I wanted enough to be helpful. Contrary to popular lore CBD is actually alerting it’s not something that enhances sleep on its own. A little bit is helpful because it can reduce anxiety that interferes with sleep but too much clearly could get people wired.
I know some people in California that use cannabidiol in the morning instead of caffeine. It’s only at extreme doses that CBD is actually sedating and usually in combination with other medicines.
Something unique about the Daygold line is all the products contain some CBG, cannabigerol. This is probably less familiar to people than cannabidiol. I like to call it the mother of all cannabinoids because it’s first in line in how the plant makes these chemicals.
Normally the plant doesn’t stop there it goes right on to the others but plants have been developed particularly in the Pacific Northwest that make a lot of CBG and sometimes only CBG meaning they have mutations that prevent them from going on to make THC and CBD.
What we’ve come to learn both from laboratory results and now people using CBG is that it’s a very effective agent for anxiety and without being sedating, habit forming or any of these types of problems.
It really can enhance other cannabinoid blends and particularly in the case of trying to reduce THC associated side effects which CBD does too.
I tend to think the combination of CBD and CBG is really helpful. They have some similarities and they have some distinctions, but strength in numbers. A lot of people just do better with these complex mixtures and that certainly applies to the terpenoid components. We don’t see a lot of plants that produce 90 [components] of one thing; it’s often 60 or less and then sometimes a hundred minor components.
Liz: Really interesting. So let’s see, we’ve talked about the entourage effect. While there are so many CBD solutions on the market, every day it seems as though there’s a new product. In general, what would you recommend a healthcare practitioner to advise their patients to look for in a CBD solution?
Dr. Russo: Well it’s a tough one especially because in a given area there may not be a lot of choices except what’s on the internet. Most often those are going to be isolates and there are real quality control problems in the industry. What’s on the label may not be reflected in what’s in the bottle.
So, first of all there’s got to be enough [cannabinoids]. I think I mentioned earlier…CBD is great but sometimes you need more numbers and the isolates tend to be very expensive if there’s a high dose involved. So it’s very tough to say. Generally speaking five milligrams of CBD isn’t going to do a lot on its own. Twenty five or more…now you’re talking. It’s more likely to have a benefit but I think CBD does better with friends along for the ride.
Liz: You mentioned a couple things; one is safety. That’s something that Daygold [offers]—and you do find many brands do have their certificate of analysis, but not all do. I would definitely say that you want to buy a product that has a certificate of analysis that is done by an independent lab. That’s what we’ve done and it shows exactly what’s in the product and these are the percentages and what we’ve done, and I think is standard with a COA is to make sure there are no solvents, heavy metals, pesticides in the product, so that’s super important. And then Daygold follows a lot of safety protocols—and many companies are starting to to do that as well—but again that’s not across the board.
Dr. Russo: And one way to ensure that is [to check] that the product’s been made according to GMP (Good Manufacturing Practice) as Daygold is. So, yeah quality control and proof of what’s inside is really a necessity.
Liz: Really important. And then of course you know you spoke to it as “having friends along”. Having a solution that does have a little bit of THC and some terpenes in it, along with the cannabidiol and cannabigerol and other lesser known cannabinoids. How would you recommend for people to try CBD for the first time?
Dr. Russo: Again, very difficult. Usually people seek guidance from their doctor. As we’ve mentioned because of a lack of medical education about cannabis and the endocannabinoid system many doctors are not familiar with this area.
I’ve studied this for 25 years and I’m still learning every day. It’s not a simple thing to learn, but I think that people benefit not from the isolates and more from what are called broad-spectrum agents or full-spectrum agents that have other components in them. And again, who made it and why…you know is there a rationale for it.
We can talk more about why this formulation was done this way. I tried to apply science more often. I’m afraid for many companies it’s a matter of having some material so that’s what’s in it.
Liz: Regarding dosing: is there a minimum and maximum? We recommend with Daygold that you start with 0.5 milliliters and I know you’ve said you like to start low and go slow but what recommendations do you have beyond that for somebody who is new to trying CBD?
Dr. Russo: Yeah that’s the point. There’s a difference in what’s called tolerance. If someone, for example, is a daily cannabis smoker they’re going to be getting large amounts of THC in particular and wouldn’t likely feel so much at that starter dose of half a milliliter of material.
In contrast, for somebody new to this who’s worried about taking cannabis-based medicine half a milliliter is going to be really likely quite good for them. It would usually be below the amount that someone’s going to feel from the THC. Hopefully though they’ll feel the benefits so I think that is a good place to start.
It’s also, for many people, a good place to end if it’s producing the desired effect. One of the beauties of cannabis-based medicine— particularly with low doses—there isn’t the development of tolerance. That’s a way of saying if you’re treating pain and this dose was adequate it should remain so over the long term short of your condition getting worse of course. And even then that’s not always the case for some people they may do better with a full milliliter but that’s where I’d keep it for most people unless there’s a compelling need to go higher and with the caveat that the one milliliter dose didn’t produce unwanted psychoactive effects.
At the one milliliter level a couple of the formulations would have enough THC in them for the occasional person to feel a little unusual or get a little anxious, but not often. People are remarkably different in the amount that gives them problems but we want to avoid that so it’s always better to under estimate rather than overestimate.
And again, I would not recommend that most people exceed a full milliliter two or three times a day. Now with the sleep preparation, usually just taking it at night so that’s once once a day but for Calm Mind in particular for most people the smaller dose half a milliliter or a full milliliter twice a day maximum, three times a day very likely is going to be helpful to them.
Liz: I find Calm Mind to be very helpful to me. I take half a milliliter in the morning as part of my morning ritual and something that I would love to hear your thoughts on is…I have sort of a ritual around how I take it. I open the bottle and I do like to take in the aroma—I think it’s really a lovely smell—and so would love to know what you think about the idea that I have that I’m taking in these beneficial terpenes through my nose and then I place it under my tongue and I hold it under my tongue and while I do that I connect with my body. I check in with how I’m feeling and I also think about you, to be honest, and I think about all the research that you’ve done and the intention that has gone into this formula and that I’m nurturing myself by taking it. It’s organic coconut oil, it’s got well-sourced cannabinoids and terpenes and so I think about that because I believe in the power of the placebo effect. You know the fact is that if we really believe in what we’re doing it can help benefit and have its own boosting effect.
But, just curious what you think about about taking in a little bit of the aroma?
Dr. Russo: Yeah that’s great and for people that would like to follow this kind of regimen, it’s likely going to be very successful for them, but specifically smelling the formula.
I’d really encourage that because inhalation is a really efficient way of getting the terpenoids in. Most people think of that in terms of vaporization or smoking. We wanted products that didn’t need to be smoked. When terpenoids are taken orally they’re slower in onset and it’s not quite as pronounced, so the two steps of smelling will be helpful. Keeping it in the mouth—which will allow some absorption from the mucous membranes, as opposed to waiting for digestion—it’s going to be helpful.
Liz: Do you have any thoughts around how long you should keep the dose under your tongue if you are going that direction?
Dr. Russo: A minute or two is plenty—just as long as it’s comfortable.
You know, I think many people are going to like the taste—you can tell that there’s a lot of real plant material in there. You know it’s not sweetened or gussied up in a way that’s artificial or in a way people are going to find to be a problem for them. A lot of people have told me they really like the taste. That wasn’t something I necessarily expected but good to have happen.
Liz: It is an unusual, lovely, aroma and flavor. I have tried other CBD products with success. I’ve enjoyed them, too, and I like the flavor of cannabis but it’s not something like Daygold. Daygold is so much nicer to take in. So even though it wasn’t intentional it really ended up being lovely.
In terms of dosing—I just want to make sure that I’ve asked all these questions. What if you were to take too much CBD? Like let’s say somebody were to take more than that three milliliters in a day, what might be some of the side effects?
Dr. Russo: Well the side effects wouldn’t likely be attributable to to CBD. It would be due to the small amount of THC. Again, let’s emphasize that the concentration of THC is a legal amount is currently set by the government on in the 2018 farm bill.
But taking too much CBD is likely not possible with these preparations. If someone had too much THC they could get anxious, their heart could be racing a little bit—what we call tachycardia—they might get a little dry mouth. So it’d be the things that one commonly associates with too much THC from cannabis.
Liz: So are there any side effects of from too many terpenes? Because we do boast a lot of terpenes in Daygold.
Dr. Russo: Not usually. Some of the formulations have mrycene in them that can be sedating. You want that for a sleep preparation, you don’t want that if you’re trying to work through pain or be able to study. Some of the terpenes may have toxicity at high doses. For example, pinene. Too much on the skin or too much inhaled can be irritating, but the amounts we’ve used are low enough to avoid these kinds of pitfalls.
Liz: Lovely, that is fantastic. Okay so if people are on other medications, what should they be aware of with taking a product like Daygold or other CBD products? And then are there, you know, if there are contraindications. Where would you direct a health care practitioner or people to go learn more?
Dr. Russo: Sure, it’s usually not a problem. One thing I learned during my time in the industry developing cannabis-based pharmaceuticals was that there is no drug that you cannot use with cannabis. We would have people be careful about additive sedative effects. If they were on an antidepressant they might want to start a product like this or any other more slowly to see how the mix goes. At extreme doses cannabidiol can produce drug-drug interactions: affect how other drugs are metabolized—broken down in the body—but that should not be an issue with anything that we’re talking about here.
Liz: Can we talk a little bit about the best way to maintain your CBD so that it will last as long as possible? Refrigeration versus [room temperature]. What would you recommend?
Dr. Russo: These products provide 30 milliliters. If someone used it every day at the recommended doses, it’s going to last a month and there shouldn’t be any issue. It should not be stored near heat or in direct sunlight, for example. For someone who’s using one of the products only intermittently it’s going to last a lot longer and it’d be a great idea to keep it in the fridge because that is well-known to preserve both cannabinoids and terpenoids nicely.
Liz: You were saying earlier that you’ve had some essential oils for over 20 years.
Dr. Russo: It’s not usually recommended. I’m sure the manufacturers would prefer that you replenish the supply every couple of years but my stash of essential oils has been in the refrigerator for 20 years and many of them still smell very nice.
Liz: That’s amazing. Well, I think those are all my questions. I had talked to a number of healthcare providers that I know—ranging from doctors, nurses, pharmacists, chiropractors, acupuncturists—and that’s where I got these questions for you today. Is there anything that you anything else you’d like to add?
Dr. Russo: Well, just to reinforce some concepts; you know we’ve tried to formulate these medicines in a very scientific way with an eye towards what people would want, that would be helpful. And again, safety above all else; I hope we’ve achieved that. The feedback I’ve gotten so far is very, very good.
Liz: Yes, well congratulations on making such a lovely formula. We are thrilled to be working with you. Thank you so much for your time Dr Russo.
Dr. Russo: My pleasure.