8 Epidiolex (CBD) Interactions to Be Aware of
Key takeaways:
Epidiolex (cannabidiol) is a cannabis-based medication that treats certain types of seizures. It’s best to avoid sedatives, such as alcohol and benzodiazepines, with Epidiolex due to an increased risk of drowsiness and sedation.
Epidiolex can raise the levels of caffeine, some anti-seizure medications, and everolimus in the body. It can also interact with digoxin and bupropion in the same way.
Over-the-counter CBD (cannabidiol) products contain the same active ingredient as Epidiolex. So they can interact with the same medications. But OTC CBD products have additional risks to consider and shouldn’t take the place of prescription medication.
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Table of contents
Epidiolex (cannabidiol) is an oral liquid medication that treats certain seizure disorders in adults and children ages 1 year and older. It’s a prescription form of an active ingredient found in the cannabis plant — cannabidiol, commonly referred to as CBD.
Like most medications, Epidiolex has interactions to be aware of before taking it. And these can apply to over-the-counter CBD products, too. Let’s take a look at eight Epidiolex interactions in closer detail to help you know more about what substances you shouldn’t take with CBD.
1. Valproates
Valproates include two types of medication: Depakene (valproic acid) and Depakote (divalproex sodium). These medications are often prescribed for seizure disorders, similar to Epidiolex. But the combination can raise the risk of liver problems. And the risk may go up if you’re also taking the seizure medication clobazam (Onfi, Sympazan) along with valproate and Epidiolex.
In most cases, this interaction is managed by lowering your dose of Epidiolex or the valproate you’re taking. Your prescriber will likely check your liver function before you start taking Epidiolex and at least 1, 3, and 6 months after starting treatment. This will help them proactively notice any changes and make changes to your medications, if needed.
But if you notice symptoms of liver problems, such as unexplained nausea and vomiting, dark-colored urine, and yellowing of the skin and eyes (jaundice), seek medical care right away.
2. Alcohol
A common Epidiolex side effect is feeling sleepy or sedated. Combining Epidiolex with other sedatives, such as alcohol, can worsen this side effect. So it’s best to limit or avoid alcohol while you’re taking it.
Keep in mind that alcohol can also increase your risk of seizures. So you should avoid it based on the health conditions Epidiolex treats, as well.
Talk to your healthcare team if you have questions or concerns about consuming alcohol while taking Epidiolex. They can provide support to help you reduce your drinking safely, if needed.
If you or someone you know struggles with substance use, help is available. Call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area.
3. Benzodiazepines, such as diazepam
Benzodiazepines are a group of medications that help manage a variety of health conditions, including anxiety and seizures. They work by calming the nervous system and relaxing the muscles. Common medications in this class include diazepam (Valium, Valtoco), lorazepam (Ativan), and alprazolam (Xanax).
Like alcohol, benzodiazepines have a sedative effect. So you may experience excessive sleepiness if you combine them with Epidiolex. What’s more, Epidiolex may raise the levels of certain benzodiazepines in the body, which also raises your risk of side effects.
It’s best to avoid this combination when possible. But if you need to take both medications (with your prescriber’s OK), use caution before driving or doing tasks that require alertness, such as cooking. If your child is taking these medications, keep a close eye on them to ensure they don’t fall or injure themselves if they nod off unexpectedly.
4. Caffeine
Epidiolex may prevent the liver from breaking down caffeine effectively. As a result, caffeine levels may be higher than usual. High levels of caffeine can lead to:
Increased heart rate
Increased blood pressure
Heart palpitations
Upset stomach
Feeling restless or anxious
If you consume caffeine regularly, you may want to cut back while you’re taking Epidiolex. This is especially true if you notice side effects such as those described above. If coffee is part of your morning routine, consider switching to decaf or half-caff to lessen the side effects of this interaction.
5. Other anti-seizure medications
Epidiolex can raise the levels of several different anti-seizure medications in the body, including:
Clobazam
Lamotrigine (Lamictal)
Phenytoin (Dilantin)
Stiripentol (Diacomit)
This interaction can increase the risk of side effects from these anti-seizure medications. So be sure to let your prescriber know if you notice any symptoms that are out of the ordinary if you’re taking Epidiolex with one of these medications. This could include things such as nausea, dizziness, or coordination issues. In most cases, your prescriber can manage this interaction by changing the dose of your medication.
6. Everolimus
Everolimus (Afinitor) treats certain types of cancers. Lower doses are used to help prevent organ transplant rejection under the brand name Zortress. Epidiolex can raise everolimus blood levels in the body if they’re taken together. This can put you at risk for serious side effects, including an increased risk of infection and bleeding.
Epidiolex may also raise the levels of other similar medications, such as sirolimus (Rapamune) and tacrolimus (Prograf). But these interactions don't seem to be as significant as with everolimus.
Be sure to let your prescriber know if you or your child are taking everolimus or a similar medication before you start Epidiolex. You may need a dose adjustment to prevent added side effects.
7. Digoxin
Digoxin (Lanoxin) helps manage certain heart conditions. It’s a narrow therapeutic index medication, meaning a slight change in digoxin levels can cause serious problems.
Epidiolex can raise the amount of digoxin in the bloodstream. This can lead to serious side effects, including vision changes, an irregular heart rate, and trouble breathing.
If you take digoxin, your prescriber will likely check your blood levels regularly. But they may want to check them more often when you start taking Epidiolex. This will help them know if your levels are too high and adjust your dosage if needed.
8. Gemfibrozil and fenofibrate
Gemfibrozil (Lopid) and fenofibrate (Tricor) belong to a class of medication called fibrates. They treat high cholesterol.
Epidiolex can raise the levels of fibrates in the body. This may lead to side effects such as muscle pain, stomach upset, and liver problems. Let your prescriber know you’re taking a fibrate before you start Epidiolex treatment. They may want to lower your dose. Or they may have you keep a closer eye out for unwanted side effects.
Do Epidiolex interactions apply to over-the-counter CBD?
Yes. Epidiolex is a prescription CBD product, but it contains the same ingredient as over-the-counter (OTC) CBD products. So the interactions listed above are also possible with the CBD products you purchase without a prescription.
That being said, Epidiolex is a more concentrated form of CBD than what’s typically available OTC. It contains 100 mg of CBD per 1 mL and is dosed based on your body weight. CBD products sold OTC typically contain much less CBD. So they may have a lower risk of sedation-related interactions than Epidiolex.
There are some additional things to consider when it comes to knowing what medications shouldn’t be taken with CBD purchased OTC:
OTC CBD products aren’t regulated. They may contain contaminants or other ingredients not listed on the bottle that can interact with medications you’re taking.
There aren’t FDA-approved dosages for CBD products you can purchase without a prescription. This means there aren’t clinical studies available to know what doses are safe and effective, including how they may interact with other medications.
CBD products aren’t a replacement for prescription medications. You shouldn’t try to self-treat seizures or any other health condition with CBD products — especially if your current treatment is working well for you. This raises your risk of drug interactions and other negative side effects.
If you’re considering trying a non-prescription CBD product, the best course of action is to talk to your healthcare team about the risks and benefits of them. They can also look at your medication list for any potential interactions and ensure it’s a safe option for you.
The bottom line
Epidiolex (cannabidiol) is an anti-seizure medication that’s derived from the cannabis plant. It’s best to avoid combining it with sedatives, such as alcohol or benzodiazepines, to avoid excessive drowsiness. It’s also a good idea to limit your caffeine intake since Epidiolex can raise caffeine levels in your body.
You may need a lower dose of some anti-seizure medications, everolimus, and digoxin if they’re combined with Epidiolex. It can also raise the levels of fenofibrates in the body.
CBD products sold over the counter contain the same active ingredient as Epidiolex. So the same interactions are possible. But CBD products purchased without a prescription have additional risks to consider, and they shouldn’t take the place of prescription medications without a prescriber’s OK.
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References
Chesney, E., et al. (2020). Lack of evidence for the effectiveness or safety of over-the-counter cannabidiol products. Therapeutic Advances in Psychopharmacology.
David, M. N. V., et al. (2023). Digoxin. StatPearls.
Jazz Pharmaceuticals, Inc. (2023). Epidiolex [package insert].
Philliben, R. F., et al. (2023). CBD for neurologic conditions in children. Medical Home Portal.
U.S. Food and Drug Administration. (2017). FY2015 regulatory science research report: Narrow therapeutic index drugs.
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