8 Epidiolex Side Effects You Should Know About

Epidiolex (cannabidiol) is the first cannabis-based medication to be FDA approved. It’s approved for certain types of seizures in adults and children ages 1 year and older. 

The active ingredient in Epidiolex, cannabidiol (CBD), comes from the cannabis plant. Tetrahydrocannabinol (THC), another well-known chemical found in cannabis plants, is known for its psychoactive effect. But unlike THC, CBD doesn’t make you feel “high” and doesn’t lead to misuse or dependence. Even so, there are other potential side effects to consider when you’re taking Epidiolex.

Epidiolex side effects at a glance

Below is a list of both common and rare Epidiolex side effects reported in clinical studies.

Common side effects:

• Drowsiness

• Decreased appetite

• Diarrhea

• Increased liver enzymes

• Weakness and fatigue

• Skin rashes

• Sleep problems

• Increased risk of infection

Rare but serious side effects:

• Aggression or agitation

• Suicidal thoughts

• Low blood cell counts

Let’s take a closer look at eight notable Epidiolex side effects and how to manage them.

1. Drowsiness

One of the most common Epidiolex side effects is drowsiness. You may feel sleepy or more lethargic than usual while taking it. And drowsiness is more likely with higher doses of Epidiolex. Often, this side effect will improve over time as your body adjusts to the medication. But it’s best to avoid driving or other activities that require your full attention until you know how Epidiolex affects you.

Getting a good night’s sleep and regular exercise can help lessen daytime drowsiness. It’s also best to avoid alcohol or other sedating medications unless your provider recommends them.

If drowsiness is severe or doesn’t improve, let your provider know. They may want to adjust your Epidiolex dosage or when you take it to see if it helps.

2. Lower appetite

Another Epidiolex side effect to be aware of is decreased appetite. You might find that you're not as hungry as usual while you’re taking it.

While a lower appetite than usual can be concerning, it's usually not a cause for alarm. But you’ll need to make sure that you or your child are still getting enough nutrients to maintain your health. If you're not eating enough, you’re more likely to feel weak or irritable. And it can also weaken your immune system.

Some tips to help you eat when your appetite is low include:

• Stick with small portions. 

• Eat more often throughout the day.

• Save drinks for in-between meals to leave more room for food during meals.

• Eat your largest meal when your appetite is at its best.

• Get regular exercise to help stimulate hunger.

Talk to your healthcare provider if you’re concerned about nutrition while taking Epidiolex. And be sure to let them know if you notice you or your child are losing weight. They may want to make sure there’s not something more serious going on.

3. Diarrhea

Diarrhea is another common Epidiolex side effect. It’s more likely as the Epidiolex dose increases. But diarrhea tends to improve over time as your body adjusts to the medication.

Be sure to drink plenty of fluids to avoid dehydration caused by diarrhea. It may also help to avoid fatty and fried foods or other foods that may upset your stomach until diarrhea resolves.

If your diarrhea worsens or doesn’t improve, talk with your healthcare provider. They may suggest an over-the-counter diarrhea medication to help. Or they may lower your Epidiolex dosage.

Diarrhea that feels severe or happens along with a fever or stomach pain needs medical attention right away. These could be signs of an infection or other issue that needs prompt treatment.

4. Increased liver enzymes

Epidiolex may raise your liver enzyme levels. Liver enzymes measure how healthy your liver is. If they’re higher than usual, it can be a sign of liver problems. 

For most people, liver enzyme changes happen within the first 2 months of starting Epidiolex. But they can happen at any time during treatment. This side effect is more likely with higher doses of Epidiolex or when it’s taken with other medications that can cause this side effect. Examples include Depakote (divalproex) and Onfi (clobazam).

You may not know your liver enzymes are high, since they don't often cause obvious symptoms. So your provider will likely test your levels before you start taking Epidiolex and occasionally during treatment. Sometimes, liver enzymes will return to normal on their own. But you may need to stop taking Epidiolex if they’re too high.

If you notice signs or symptoms of liver damage while taking Epidiolex, let your provider know right away. This can include yellow skin or eyes (jaundice), a bloated stomach, and itchy skin.

5. Sleep problems

While Epidiolex often makes you sleepy, it can also cause insomnia or poor sleep quality for some people. It can also cause agitation or irritability during the day.

Insomnia may improve as your body gets used to the medication. Good sleep hygiene can help, too. This includes:

• Limiting caffeine and alcohol before bedtime.

• Avoid exercising late in the day.

• Avoiding screens for an hour before bedtime.

• Creating a regular sleep routine.

If you’re not able to get enough rest, let your healthcare provider know. These side effects were reported more often with lower doses of Epidiolex. So your provider may want to try raising your dose to see if it helps improve your sleep. They may also suggest trying a sleep medication if it’s appropriate for you.

6. Weakness and fatigue

Fatigue and weakness are common Epidiolex side effects too. Like drowsiness, these side effects may improve over time as your body gets used to the medication. 

Regular exercise can help boost your energy. Keep in mind that fatigue can also be a symptom of other Epidiolex side effects, such as diarrhea, sleep problems, and low appetite. So it’s good to make sure you’re staying hydrated, getting good nutrition, and sleeping enough to keep your energy levels up.

If fatigue worsens or doesn’t improve, let your healthcare provider know. They can make sure there isn’t another cause and adjust your Epidiolex dosage if needed to help. 

7. Higher risk of infections

Epidiolex can weaken your immune system. This makes it harder for your body to fight infections. So you may experience more frequent infections while taking Epidiolex.

Infections seen with Epidiolex are usually minor, such as the common cold, ear infections, and urinary tract infections. But more serious infections, such as pneumonia, can also happen.

Prevention is the best way to lower the risk of infection while you’re taking Epidiolex. Examples include washing your hands often and avoiding close contact with sick people when possible.

Contact your provider if you notice signs or symptoms of an infection, such as a fever, persistent cough, or pain when peeing. They can recommend the best treatment option for your needs.

8. Suicidal thoughts or behavior

The FDA requires a warning about an increased risk of suicidal thoughts and behaviors for all antiepileptic medications. There isn’t direct evidence that Epidiolex causes this side effect. But epilepsy itself can raise the risk for thoughts of self harm, so it’s good to be aware of it.

If you notice mood changes in yourself or your child while taking Epidiolex, let your provider know right away.

If you or someone you know is having thoughts of suicide, you’re not alone — help is available. Call the National Suicide Prevention Lifeline at 988, or text HOME to 741-741 to reach the Crisis Text Line.

When should you contact your healthcare provider about Epidiolex side effects?

Most common Epidiolex side effects are mild and get better over time. But don’t hesitate to let your healthcare provider know if any side effects don’t go away or get worse over time.

You should seek medical care if you notice any signs of infection or liver damage while you’re taking Epidiolex. And if suicidal thoughts or behaviors appear, it’s best to get help as soon as possible.

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Written by:

Alex Evans, PharmD, MBA

Alex Evans, PharmD, MBA, has been a pharmacist for 12 years. His first job was floating in a community chain pharmacy.

Edited by:

Stacia Woodcock, PharmD

Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.

Reviewed by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

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