Craig Erickson, MD, the Director of the Cincinnati Fragile X Research and Treatment Center was asked by the National Fragile X Foundation (NFXF) to discuss the use of cannabidiol (CBD) for people with Fragile X syndrome (FXS) – to answer the questions around, Can I Use CBD to treat Fragile X syndrome. His full 30 minute webinar is viewable for free here, but we also condensed the information he shared into a Frequently Asked Question format below. We know there are many, many questions on the use of CBD to treat Fragile X syndrome. We hope this information is helpful.
You might also be interested to know there is currently a clinical trial of a synthetic CBD oil that is recruiting for participants. For more information and to apply for consideration, please visit this page.
Dr. Erickson ended the webinar reminded the audience that we are not endorsing the use of CBD supplements or clinical trial participation or anything for individuals living with FXS. He wants everyone to discuss their proposed use of CBD with their personal physician who is working with their child or loved one impacted by FXS because it’s an important decision.
The cannabis plant (also known as marijuana), in nature, has both tetrahydrocannabinol (THC) and cannabidiol (CBD) in it, with THC being the psychoactive part of the plant, causing the “get high” effect. CBD, also in the cannabis plant, and under multiple studies, is believed to produce a feeling of relaxation and calm; it’s not psychoactive. So, while CBD and THC share that they originally came from the same kind of plant, they are mechanistically and otherwise completely different.
The cannabis plants can be altered over time to not contain THC or the THC can be removed, and CBD can be made synthetically so it does not come from a plant.
Note: The CBD being studied in the Zynerba clinical trial in Fragile X syndrome (FXS) is synthetically made, so it is not even the CBD from an original cannabis plant.
In 2018, the United States Federal Government passed the Farm Bill of 2018 that essentially removed regulations on cannabis not containing THC. This means the THC-free cannabis products are free from the regulations that apply to THC or more classic marijuana products. That is the reason why we see CBD everywhere, because non-THC containing cannabis products are not going to be regulated like they have THC in them, long term.
There are, however, currently, state by state differences and regulations. You need to check your state.
Important: there is some CBD that has THC in it and some CBD that does not have THC in it. In states where regular marijuana is legalized, for example, in Colorado or California, among others, you can very easily find a product that has CBD and THC in it and readily purchase that. In states where THC is essentially still illegal, or remanded to only medical use, if you get over the counter CBD it really should not have THC in it.
The problem that we run into is that the CBD you can buy is essentially a supplement product. This means if you buy CBD as supplement, it is not regulated to normal FDA drug standards. There can be trace impurities, and there can be very small amounts of THC in a CBD product.
In fact, we have had a couple of families giving their child, what they thought was, just CBD that, when you read the label, may have had very small amounts of THC in it, and their child tested positive for THC. I always counsel families that there’s not a guarantee that over the counter CBD is completely THC free.
Now with that said, I have never heard of a case, in my experience, of people taking CBD oil or gummies that were not supposed to have THC in it, that their child “got high” or had abnormal reaction. I do not think there’s a clinical THC risk of a THC-like abnormal response. But there could be traced amounts of THC in with CBD.
Make sure the product you are thinking of using has been third-party tested, to ensure what they say is in the oil/gummy, is in the oil/gummy. If it does not say on the bottle, send the company an email and ask.
That is ever changing, on a weekly basis.
I would recommend that families consult their local developmental disability caseworker and ask that question.
I don’t think that’s fully understood. CBD is undergoing extensive study, not only in Fragile X, but it’s already FDA approved to treat Lennox-Gastaut epilepsy. It’s also being studied in anxiety disorders, Post Traumatic Stress Disorder (PTSD), and various addiction syndromes and disorders.
The thought is that CBD may have some properties that reduce anxiety. When families come in for an appointment and their child is taking a CBD product, a lot of what they talk about is targeting anxiety. We have had a lot of families start with the oils, and generally, they were hoping to reduce anxiety.
My thoughts are, if anxiety is significantly improved, a lot of other things may get better too. I think the problem is, we just don’t know if the CBD that is available, is going to have this effect or not.
I have had families taking CBD for years, first starting via the internet, when it was still a little sketchy with state enforcement and maybe wasn’t letter of the law, non-legal in certain states, and people still tried it. I would have to say the first reports I heard in clinic from families who were trying CBD, were not uniformly positive. I never really heard of any severe side effects or problems or abnormalities, and CBD has a profile of not having a toxic effect on organ systems, and has a pretty good safety profile, but I didn’t really hear a lot of positive things.
Caution: not all dosing is equal. More recently, Zynerba Pharmaceuticals has been studying a CBD topical gel at doses of 250 milligrams a day of the gel for individuals who weigh less than 35 kilograms (~75 lbs.) or 500 milligrams a day, for people who weigh over 35 kilograms (over 75 lbs.). I think the first thing to realize is, that’s a pretty hefty dose that is under study, in a well-designed study, in youth with Fragile X. It is a much higher dose then you would typically take over the counter.
For example, I looked up some of the CBD gummies and they state they are 25 mg CBD per gummy. For equivalent dosing, and it’s not perfectly equivalent because there are differences between a gel on your skin and swallowing it, but an oral CBD gummy may have 25 mg of CBD, so that would be 20 gummies a day to get that higher, over 75 pound person, dosing (>500 mg) of cannabidiol.
We are certainly not telling people to take that many gummies a day.
I think there are some potency differences that need to be accounted for and can make it very tricky to take CBD over the counter. I’m not here to endorse CBD use or make any specific recommendations, but there are some dosing differences that make this a real challenge.
Yes. I would recommend that any parent/caregiver/family member of an individual with FXS tell their prescriber, medical doctor, or whoever may be writing for medications for them or providing medical care, that their child is taking CBD, because it can impact liver metabolism of a number of different drugs via liver enzymes, and it can have an impact on some of the other behavioral medicine your child may be taking.
CBD can compete for liver metabolism that can potentially increase levels of other drugs, as it may “use up the system”, so to speak, in drug metabolism. That can be a real issue. There are also some rare reports of other conditions, like people that have bleeding diseases, or are they coagulate too much, and they take a medicine called Warfarin or Coumadin, and then they take a cannabidiol, it really messes with their Warfarin levels. That probably doesn’t apply to a lot of today’s audience, but it’s a key example of how CBD can impact dosing and metabolism of other drugs. That is one of many reasons why I would really encourage you to share with your provider if you’re caring for an individual who’s taking CBD. I think it’s very important.
There is a drug called Epidiolex that is FDA approved, and it is a CBD approved for severe seizure disorders.
If your child has seizures talk to his/her neurologist, or their epilepsy doctor, to see if prescription CBD would be suited for them because it can be helpful for some severe seizure disorders and probably not as helpful for others.
I do not prescribe Epidiolex. I leave that to seizure or epilepsy doctors who we collaborate with. There are definitely some dosing differences with seizures and other indications.
Do the clinical trial, if you can. It is good science and is enrolling all over the country. It is an important trial.
But what if your child is found to not be eligible for the clinical trial? Or what if what if they’re out of the age range?
Have a conversation with your child’s physician and ask about CBD. I would say that the feedback I get from families is the changes in recent years where they are putting CBD in a form like gummies have made it a lot easier to take than the oils, tolerability has been improved. There’s no evidence of organ toxicity.
There is the potential to show interaction with other drug metabolism. So that’s an important thing to talk about. We don’t really know what the dosing should be. We are studying pretty high dosing in the clinical trial compared to what it is going to say on the bottle of CBD. But at the same time, we don’t really want people going off and taking 10 times what it says on a bottle they get over the counter.
In this kind of situation, I tell families – I’m not going to tell you that I think CBD is going to hurt your child, if you’re following the basic recommendations on a bottle. I have never heard of an incident of a severe adverse reaction, and I don’t think there’s any good evidence it is toxic to your body. At the same time, I don’t know if it’s going to do anything to help. So, we’re just really honest about that. Reducing anxiety would be awesome if it happened, but we’re not sure.
As long as people are aware of the risk, with drug metabolism, and they are aware of the small risk of impurities, because it is a supplement, and it is not perfectly regulated, then I don’t have a problem with families trying CBD, and in particular, if they can obtain it fully legally without any associated risk.
I do ask families, if you are going to start this, be upfront about it, tell us what form you are taking, tell us what the dose is, bring the bottle in and we’re happy to look at it. Then at least we can partner with families and knowing what they’re taking, we move forward from there.
The other thing I tell families, the same thing we would do in a clinical trial, it is always good to have healthy skepticism, because we all want individuals to do better – your FX doctors want it, families want it, and therapists want it. It is easy to start anything and then “will” things to be better. So, have a healthy skepticism and say, “Maybe we should try it when we’re not changing other medications. Try it when there’s not a lot of other changes in our lives or the life of my child – though that is sometimes easier said than done.
Also, think ahead of time — If this new treatment was working, what would we want to see improved? And then asked yourself – is that any different? That’s a nice way of starting any new treatments; for example, make a list of what we think anxiety is as we observe it in the family, as we see it in our family member impacted by FXS. How do we see it? And then once he/she is on the CBD, is it different?
Maybe get input from others around you, other family members, school, therapist, and try to get a feel for it. So if you’re going to try something, try to do it in a regimented way if you can, because it’s very easy in my career, the last 15 plus years, we’ve done this a lot as clinicians, we try something new, we’re excited about it, and then we just have rose colored glasses, and we think things are better.
So, we don’t want to be negative, but we want to just be very rational, and try to think ahead of time, if something was better, how would that be? In a quantifiable way? For example, would your son or daughter be able to follow a one-step command? Would they be able to sit in their desk for more than two minutes at a time in school? Would they reduce their biting of their wrist or hand? In certain situations, are they able to tolerate sitting down at dinner at a preferred restaurant? Think about some tangible aspects and then see if that’s better. That sounds simple, but I think that’s a targeted way to look at new treatment, if you’re doing a trial, or something like CBD over the counter. That approach really makes really make sense.
This is a hard question. I think in one day, there’s probably a new CBD manufacturer. The key is to try to get the purest form; read the ingredients on the bottle — you want no trace of THC. And you want the product third-party tested.
But you know, it’s kind of the wild west on CBD. It’s all over the place. Today we can talk about manufacturer X, and tomorrow, we would talk about Y & Z, and it’s a challenge. So, I think trying to get as pure as you can make sense — trying to avoid any trace THC makes sense.
The feedback, I’ve gotten from families, is that gummies are a lot easier to take, and that intuitively makes a lot of sense to me. I think the oils, how long you keep in your mouth and under your tongue. I think if all is equal, the feedback I’ve heard is that the gummies are an easier way to go.
We were asked about making your own CBD capsules. I’m not sure about that. I think if you are trying to take the oil and put it in a capsule form, I think that would add a layer of complexity to it. Hopefully the other formulations like the edible forms of CBD alone will work.
I think the honest answer is people aren’t exactly sure. The half-life for the time to have maximum levels in your system is not extremely well established in these formulations. As I said earlier, the gummy dosing on bottles is generally pretty low. You know, we’ve had families give some positive reports of taking gummies twice a day as that tends to be what it says on the bottle. I don’t have any reason to give different advice, but at the same time, we just don’t have good data.
So again, it’s one of those things that I think you’re best served to really look at things with that healthy skepticism, and if you feel like things are very helpful for a few hours, and then wear off, maybe you adjust your dosing interval, but you want to do that with some data and tracking to see if they change with your child to give you justification, to really up the frequency to something like every few hours, because it’s hard to remember to take anything every few hours. But again, you know, we don’t have great evidence on the spacing of the timing of what’s available.
As best I can tell, purchasing over the Internet legally existed before it was legalized in states. A year ago, I could have bought a ton of CBD from Amazon and had it delivered to my house. Now I’m in Ohio, last year, that was probably still technically against the law.
I think what happened is, the law may not legally allow for something, but the law is not being enforced. Because in Ohio last year, I never heard of any enforcement issues with people purchasing CBD on Amazon. So, in that sense, if your state allows you to go down the street and buy it, it’s probably not different if you order it on the Internet.
Now I read articles that say CBD is going to be hitting major grocery stores, places like Target and Walmart, and so we’re going to see it everywhere. Once it is everywhere, it is like the cat’s out of the bag, as far as regulating it.
I don’t think overdose is very well established. I think toxicity studies show that there’s not a lot of organ toxicity, it isn’t going to hurt your kidneys or your liver or your thyroid, there’s not a lot of evidence that it causes weight gain and there is no evidence that it causes addiction or that you can get dependent on CBD, specifically. But any medication, whether it’s a supplement or whatever, you can be allergic to it. Anything that’s having an effect on your brain could cause negative behavioral changes. We haven’t heard a lot about that, but I would always recommend people monitor for it.
Any medicine or supplement can cause things like headaches and upset stomach, but overall CBD is well tolerated. I don’t think we’ve had a family come in yet and said they had to stop it because of some weird tolerability issue, and I have always wondered if that is because the dosing is so low of what you can purchase. Maybe, but I don’t know that.
There are some good sources, and some nice scientific review articles written on CBD that are readily and freely available through the National Institutes of Health, who has an online search directory, and I’ll work with the NFXF to get some links to some good scientific reviews that talk about CBD and a lot of different disorders. They highlight a lot of the uncertainty I was talking about.
Anyone selling CBD wants you to buy their CBD product. So, going to third-party sources, like some of these scientific reviews and articles can be helpful to get more information.
That is a tough question. I think sharing experiences can be very helpful. I think when you start a new treatment, whether it’s CBD or anything, whether it’s a prescription drug, whether your child is in a study or not in a study, you just want to really think about what you would like to see improved. What can improve their quality of life? How are you going to quantify it? Who do you want information from – do you want it from the school, do you want it from a different family member, do you want it from some relative you see every couple of weeks, because maybe change will happen and they’ll notice it because it’s not incremental. Whatever it may be – just have a method to the approach of wondering if things are better, because if things aren’t better, there’s no reason to continue these treatments necessarily long term.
I would certainly think the information on social media could help with tolerability. How did your child take something? Did it taste awful? Those kind of things on Facebook could be helpful.
I would say a month or two is probably good enough to see an effect with CBD.
There are several trials going on mental health and anxiety disorders, addiction disorders, and post-traumatic stress disorder and other conditions. There’s of course, the Fragile X Zynerba trial ongoing, that I’d encourage people to consider if they’re interested in CBD, and they have a child in the youth age range.
Go to clinicaltrials.gov, and type in CBD in the first box, and you will get several trials and information.
If you put in CBD and in the next block you put in Fragile X, you’ll get some good, unbiased, federally approved language about the Zynerba trial, including that dosage information I talked about earlier.
That is all freely available information, and I recommend people look at it for more information.
If you look this up on the Internet, you will hear about a lot of them, but I don’t have a lot of faith in them. I think there’s some risks of drug-drug interactions. For herbal supplements for anxiety, I think you don’t really know what you’re taking is the challenge. There’s nothing I would specifically mention, or that I think there’s some solid scientific data behind it. I think CBD – while there’s a ton more unknown than known, at least I think we have a place to start for people interested in giving it a try.