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Dr. Mike Smith. (Host): There are few subjects that can stir up stronger emotions among doctors, scientists, researchers, policymakers, and the public than medical cannabis. Welcome to The GW Hospital HealthCast. I’m Dr. Mike Smith, and today's topic, The Benefits of Medical Cannabis. My guest is Dr. Mikhail Kogan. Dr. Kogan is the Medical Director at the George Washington Center for Integrative Medicine and Assistant Professor of Medicine at the George Washington University School of Medicine and Health Sciences. Dr. Kogan, welcome to the show.

Dr. Mikhail Kogan (Guest): Thank you. I'm happy to be here.

Host: So, this is a big topic, right? There's a lot of debate about the role of medical cannabis, and even some confusion about what is medical cannabis versus every day, casual smoking of cannabis. Maybe you can help to kind of clear the confusion for us first. First of all, what's the difference between medical cannabis and what people smoke every day for leisure?

Dr. Kogan: Right. I think that's a really important question to start out with. Traditionally, there are two ingredients that are most commonly prevalent in the cannabis plant, and that's the THC or tetrahydrocannabinol, which is what everybody's looking for when they're trying to get psychoactive or recreational use. That's what makes people high. Typically, when you buy a product on the street or in the recreational dispensary, you're going to get a product that has a very high percent of THC. Now, it's even more confusing to say that THC does have a number of medicinal properties, but since we're just answering this first question, THC is primarily for recreational use.

When you're talking about the medical use THC is probably going to be there, but you're starting to look at other cannabinoids, and the second most common one is what's called CBD or cannabidiol. Typically, for medical use, we will have some combination of several ingredients, and the two most prominent ones are THC and CBD. Once you start having CBD percent or a ratio of CBD to THC — which is how we often will talk about medical use — is going up. Once the ratio reaches a certain — say, maybe 2:1 or 4:1, no matter how much THC you take it's very unlikely you're going to have any psychoactive or any high. In that sense, that's the most important separation.

Host: Right.

Dr. Kogan: There are also routes of administration. Usually, people smoke cannabis to get high versus when we use it medically, we use it topically; we can use it rectally. We can use it as a sublingual drop, as edibles also. And to some degree, of course, as well inhalation form, but less smoking and more vaporizing.

Host: Right, right. Just to kind of summarize for the audience, the medical cannabis is going to have a higher amount of the CBD versus the THC versus if you smoke it leisurely, you're going to get more of that THC. Medical cannabis has higher amounts of CBD. Why is that? What is it about CBD? What have we learned recently in the research that makes us think that this is a medicinal compound?

Dr. Kogan: Well, I think — let me clarify a couple of things here. It is very confusing, actually, because as I said, THC does have quite a substantial amount of medical utilization as well. It's really the intent of the use. And while yes, generally speaking, you need some CBD to kind of offset the THC high, but again, THC compounds alone are used. CBD itself is a pretty potent anti-inflammatory substance. In fact, it recently — I would probably say a month ago — has been FDA-approved as a medication for seizure disorder for certain populations in complex seizure conditions. So, there's already official medical use for CBD for at least one condition.

We use it a lot for — again, it's obviously off-label — but we use it for anxiety; we use it for sleep, and even topically, for pain. I think if I start carefully going through the possible list of indications, the list will be very long.

Host: Right.

Dr. Kogan: I think it's important to mention also that typically, most of us who have some experience in this field will probably utilize multiple cannabinoids at the same time. We will not use just CBD. We will combine CBD with THC or other ingredients. And also, there's this idea of Entourage Effect when you add components that are originally in cannabis. It's a small amount, but when they combine with the main ingredient, there's somehow a potentiation of the effect. That's called the Entourage Effect, and you can have a whole extract of the cannabis plant, and it's actually going to be more efficacious than if you just apply let's say only CBD alone or just THC alone.

Host: Just one, right.

Dr. Kogan: I think this is an unusual scenario where both medicinal plant medicine, as well as medication, will coexist.

Host: Dr. Kogan, I think maybe the listening audience might appreciate a little education on the cannabinoids themselves. I think a lot of listeners are familiar with the sympathetic nervous system, the parasympathetic nervous system, cortisol, and the stress response. We hear about all of that a lot, but there's another system in the body called the endocannabinoid system. Can you teach us a little bit about that, and why is that of such interest to physicians like yourself?

Dr. Kogan: Right, well, it's the oldest system we have. Actually, it's a lot older and a lot more prevalent compared to let's say the endorphin system, which is what we use things like morphine. The system is quite robust. It's present in every cell of our body. There are a couple of different receptors, primarily CB1 and CB2 receptors that we're talking. CB1 receptors are present in the central nervous system and CB2 in lots of other places. Most importantly, actually, it's a very strong regulator of the immune system and also, inflammatory responses. We know that cannabinoids — endogenous cannabinoids, and the most common one is anandamide — have regulatory mechanisms to control inflammation, to control and balance our immune system, and you also mentioned the hormonal system.

What's fascinating — and I don't know why that's made this way — is that we have almost no receptors in the brain stem. That's what’s responsible for a very high level of safety. Cannabis — in fact, it hasn't ever been described that anyone has died from using cannabis at any dose. That's probably because we don't have any breathing suppression no matter how much cannabis you use.

Host: Oh, okay.

Dr. Kogan: The THC, which is the psychoactive ingredient, is very similar to our endogenous anandamide. We have an exogenous molecule from plants that can induce a very similar effect that our own anandamide can. Of course, you can take a lot more of it exogenously to induce the high, which normally we don't get from our own endogenous system. And then CBD interestingly does not directly affect the receptor. It does, but it doesn't really have a potent effect. It rather modulates or changes the effect of THC and exudes its efficacy in some indirect way. And actually, it's not really fully elucidated. I would say the science of the endocannabinoid system is fascinating. It's very rapidly changing. We're learning a lot, and yet, we still don't have a lot of clinical answers.

That's a cautionary tale. There's a lot of hype. People use all kinds of products for all kinds of reasons. There's a lot of different hemp products with the CBD, and there are claims on the internet on anything from cancer cures and all kinds of condition cures. There may be cases, but unfortunately, the actual clinical data is lagging. That's really unfortunate because I think the potential here is really big. I hope that our politics are changing, so at least providers can start doing clinical studies.

Host: Right, right. And you believe based on what we see in the preclinical and some of these anecdotal stories that there's real potential for medical cannabis to be a powerful treatment tool for probably several different types of disorders? Just to kind of summarize here, of all the different benefits that you believe medical cannabis is potentially helpful for, what's maybe the top benefit that you think really we need to start studying and developing clinical trials for?

Dr. Kogan: Well, let me first give you just a quick summary of what's already proven, and then let's go into what I feel would be the next level of research and where I think the cannabinoids can have a really strong impact. I think chronic pain — and this is more specifically for things like fibromyalgia, chronic fatigue syndrome, neuropathic pain, those types of hard to treat pains — I don't think there's any more research needed. We need research to figure out the dosing, but the current data is very clear. In 2017, reports put out by National Academies of Sciences had been conclusive. They give a Grade A recommendation use in chorionic pain, which literally — they're saying that we should be using it as a prescriber almost as a first line.

I would also say that cancer symptoms — nausea, vomiting, appetite — that's also a very important role. It's quite conclusive, as well. And a third would be spasticity from different conditions like Multiple Sclerosis, certain bowel disorders that present with a high amount of spasticity and spasm, so something like irritable bowel syndrome.

And the next level of clinical research I hope will be in a couple of directions, and they're primarily all inflammatory conditions, so maybe IBD, inflammatory bowel disease, maybe neurodegenerative conditions such as Alzheimer's and Parkinson's. Of course, there's a very large amount of interest among the public in using cannabis as a disease-modifying approach for cancer. That's very controversial. There's a lot of potential because if you look at the preclinical animal studies and in vitro studies — Petri dishes — there seems to be a very strong anti-cancer effect. Will that translate to the clinical data in humans? It's hard to say, and I would definitely slow down the hype out there to say you really can't use something yet. Hopefully soon, once we have trials going and have results.

Host: Right. Well, what a fascinating topic, Dr. Kogan. I want to thank you for the work that you're doing, and also, thank you for coming on the show today. You're listening to The GW Hospital HealthCast. For more information, go to GWDocs.com, that's GWDocs.com. I'm Dr. Mike Smith. Thanks for listening.