Transcription:

Melanie Cole (Host): According to the Journal of Pediatric Pharmacology and Therapeutics, medical marijuana use has recently become a hot topic, not only within the medical community but also at state and national levels. This is part one of our three part series for providers on cannabinoid use in pediatrics. My guest is Dr. Jennifer Griffith. She’s a Washington University Pediatric Neurologist at St. Louis Children’s Hospital. Dr. Griffith, I’m so glad to have you with us. What a great topic for a series. Tell us a little bit about CBD. What is it and how does it work?

Jennifer Griffith, MD, PhD (Guest): That’s really the ultimate question. What is CBD? So, let me start by just saying as you said, CBD stands for cannabidiol, so this is one chemical of over 100 that’s found in the cannabis plant. And cannabis is synonymous with many things including marijuana and CBD specifically refers to one substance that has potential for benefit in neurologic disease.

So, the cannabis plant actually there are many different strains and there are those that have a very small content of the psychoactive substance THC which is tetrahydrocannabinol. And those that have a very small less than 0.3% content of THC are classified as hemp. So, many people have heard of the hemp plant and know that it has many uses both in industry as well as in pharmaceuticals and so hemp is one of several strains of the cannabis plant.

And then, there’s also marijuana which is thought of as the psychoactive drug that people smoke or use in other ways to get high. And those have a much higher content of THC. So, when we are talking about CBD, we are specifically referring to one of the cannabinoids that’s not the psychoactive part of the marijuana or of the cannabis or the hemp plant.

And there are various ways to take the cannabis plant and then extract it into the various compounds and specifically when you take the hemp plant which again has a very low THC content and you extract form it an oil, depending on the process by which you obtain that oil; you can get something that is referred to as hemp oil, you can also get something that’s referred to as CBD oil. And sort of by definition, although there’s no kind of real industry standards, although there’s some attempts to make some standards; the content of CBD oil should be again, by definition, less than 0.3% which is by federal law.

Where it gets confusing is that you can extract an oil from marijuana plants which again have a higher percentage of THC and depending on kind of the manufacturing process and how that’s labelled, that can also be referred to a cannabis oil or even in some cases, CBD oil. And since there’s not a lot of regulation on how the oils are made and how they’re marketed; it gets really confusing. But for the purposes of this talk, when I refer to CBD oil, in general, I will be referring to something that has a very low THC content. Which is important when we are talking about medicine.

Host: Well, it certainly is, and it has sparked a lot of debate, discussion, research ongoing. Tell us a little bit about the differences between CBD from local shops versus state regulated companies versus FDA approved products.

Dr. Griffith: Right. So, as I drive down the street every morning, I see advertisements popping up everywhere in Missouri for CBD shops and they are marketed all different kinds of ways. It’s kind of fascinating. Some are more health-oriented and some are very seem almost like medical supply shops and others seem kind of the more traditional pot shops. But I think the fact that we are seeing it everywhere is really kind of in line with how patients are coming to me and asking about it. So, when a patient approaches me and asks about CBD, I explain there are sort of three levels.

One is the CBD you do go down the street, pick up from your local shop who is selling a product that is at least labelled as CBD. And there are no guidelines or really any kind of assurances that what is in those products is really what is being sold. So, it’s very much caveat emptor and I tell my patients, there have been studies where they looked at many different products available online or at local shops and there’s a wide variety of both the amount of CBD in those products and also I think really importantly the amount of THC that’s found both either getting less CBD than is advertised or getting more CBD and that has really important implications for my patients in whom their other medications can interact in very important ways with CBD.

Then, the next level is a state level, state regulated kind of dispensary. So, in our audience, we are probably talking about Missouri and Illinois, both of whom have a program to sell and distribute CBD and in some forms. In Missouri, it is called the Missouri Hemp Card Program and in Illinois there is a medical marijuana card. And there are at the state level, licensed and registered manufacturers that cultivate the cannabis plant and then turn it into a CBD oil or other kinds of medical marijuana products. And those at least, there is some regulation by the state government about the manufacturing process and what is being made by those companies. Although there still are not any standards sort of similar to the FDA level where we really know that the milligrams of CBD for instance, that it says on the bottle is really what’s in that product.

And then the third tier, what I consider the highest tier is the FDA approved form of cannabidiol which is the brand name Epidiolex made by a pharmaceutical company. And though I usually like to refer to medicines by generic names again, for the purposes of this conversation, I’m going to refer to Epidiolex by its brand name because it’s the only one of its kind and I have to distinguish it from the other kinds of CBD that are available online or in local shops.

So, Epidiolex is an FDA approved drug. It is now schedule V so I can write a prescription for it. it is not available at your local pharmacy. It does go through a specialty pharmacy company. But it is available to be prescribed for patients specifically for certain neurologic conditions.

Host: Doctor, how much does CBD cost in general and is it covered by insurance?

Dr. Griffith: Yeah that’s a great question. So, the products that are available at your local shops are certainly not covered by insurance. There’s no prescription required. You just walk in and buy it like you would any other vitamin or product on the shelf. So, I can’t really speak very much to what’s in that. Those vary. There’s a wide range of formulations available and there’s a wide variety of prices to go with that. And since there’s no real assurance that what you’re getting is really what’s in the bottle; it’s sort of every man for himself.

At the dispensary level, those for my patients that have obtained those for epilepsy which is the current common indication to have CBD; my patients are usually telling me that it costs on the order of several hundred dollars per month when they give the product at the dosing recommendation that is recommended by the dispensary. And that is not covered by insurance at all. That is completely out-of-pocket. And importantly, in Missouri at least, physicians don’t write a dosing recommendation or a prescription for it, they just sign a card saying that they are following this person for epilepsy and that they believe it will have benefit. So, it’s really up to the family or the patient and the dispensary to come to some agreement about what the dosing guidelines would be.

Epidiolex does have a very specific dosing guideline. There is a starting dose, a titration schedule and a maximum recommended dose and safety monitoring guidelines. That product is at least available to be covered by insurance although depending on the insurance; it may or may not be covered and there may be various prior authorizations or other kinds of drugs that you need to have tried first before insurance will agree to cover it. The out-of-pocket cost for Epidiolex for a typical adult-sized person in on the order of $2200 per month if you prescribe it at the recommended maintenance dosing. Again, with that being covered by insurance for some patients.

Host: What a great explanation. Thank you so much Dr. Griffith. So, what pediatric conditions besides epilepsy, because we are going to talk about that in part two of our series, but are there other conditions that it can used for?

Dr. Griffith: In the United States, no. Not currently. At least not to be prescribed. Epilepsy is the only FDA approved condition and in particular, there’s really only two forms of really devastating epilepsy syndromes for which Epidiolex is able to be prescribed. However, I will say there are more than 300 trials, on www.clinicaltrials.gov the last time I looked that were in some various phase of either enrolling or of completing their data collection. So, this is something that many people are trying to see what other indications are available for CBD.

In other countries, where other forms of medical marijuana are available to be prescribed; there has been some evidence that spasticity for instance in multiple sclerosis can be treated with certain forms of CBD and or THC. And then there’s many other conditions that there is some at least preliminary evidence that there may be a role for CBD. So, things like pain, inflammatory conditions, and many psychiatric conditions including opioid dependence. I think that’s really interesting application of CBD. However, in the United States, at this time, only epilepsy is the only indication.

Host: So, as you tell us what forms the products are provided in, tell us how so, how it interacts with other prescription drugs and any side effects that you’ve seen.

Dr. Griffith: Yes, so, CBD and Epidiolex in particular are metabolized by the liver and there are known interactions with other drugs that are also metabolized by the liver. Importantly, for an epileptologist, like me, it can increase the concentration of one medication we commonly prescribe, clobazam by up to fivefold. So, the active metabolite can increase by quite a substantial amount and that may affect both management of seizures but also potential side effects.

So, there are real interactions. Many people who might be listening probably don’t prescribe clobazam but they may prescribe other things, for instance there is sub-interaction with the drug montelukast so even things that primary care providers or other subspecialists may be prescribing can have really real interactions with CBD and that’s why it’s important for our patients to let us know if they are taking any of these products whether they are prescribed or not.

When there have been trials of Epidiolex in particular because that’s the one that’s sort of been best studied, most people report some adverse effects, that’s true for many new drugs that come to market. The most common of them was fatigue and sedation. So, I have yet to have any patients of mine that have started Epidiolex who have not complained of fatigue or being more sleepy than previously. For some patients, that can get better. For others, it is a side effect that prohibits them from continuing the drug. Most of the other side effects were also dose-dependent in the drug trials. Vomiting and diarrhea was another really common one and again in some cases, prevented patients from continuing the drug.

There also is a monitoring requirement to monitor liver enzymes. Fortunately, that seems to be reversable, but it does lead to discontinuation of the drug for some patients.

Host: Dr. Griffith, as we conclude this first part of the series; does it work? And give us a little bit of a brief overview of what we can expect in the next episode on the Epilepsy Case Study.

Dr. Griffith: So, the exciting answer is that yes, it does work. But I will couch that a bit by saying not for everyone and not completely. And so that is where as epileptologists, we’ve been both optimistic but also cautious in prescribing this medication and I think that will continue to be true as we try to research other areas in which we might use CBD and other kind of related compounds.

Host: Thank you so much Dr. Griffith for all this great information. What a fascinating topic. To consult with a specialist or to learn more about services offered at St. Louis Children’s Hospital, please call Children’s Direct Physician Access Line at 1-800-678-HELP.

That wraps up episode one of our three-part series to help provide pediatric healthcare providers information for safe and appropriate use of cannabinoids. This is Radio Rounds, the podcast series with St., Louis Children’s Hospital. Head on over to our website at www.stlouischildrens.org for more information and to get connected with one of our providers. If you found this podcast as informative as I did, please share with other providers, share on your social media and be sure to check out all the other fascinating podcasts in our library. I’m Melanie Cole.