By: Aya Alrmah
Epidiolex (Cannabidiol Oral Solution)
This article is meant for educational purposes only and should not be taken as direct medical advice. For any questions or concerns, please speak to your healthcare provider.
Cannabidiol oral solution, also known as Epidiolex, is the first plant-derived antiepileptic drug (AED) approved by the U.S. Food and Drug Administration (FDA). It was approved to treat seizures caused by Lennox-Gastaut syndrome and Dravet syndrome in patients aged 2 years and older (FDA, 2018). Lennox-Gastaut syndrome is a rare type of epilepsy, affecting around 1–2% of people with epilepsy, and is characterized by multi-drug resistance (Asadi-Pooya, 2018). Dravet syndrome is a severe form of epilepsy that affects infants. Both are rare epileptic conditions and are believed to cause epileptic encephalopathy, in which ongoing epileptic activity leads to damage to the nervous system (Dulac, 2001).
Although Epidiolex is not a first-line treatment for these forms of epilepsy, it has been shown to be effective in decreasing seizure frequency (Abu-Sawwa et al., 2020). It is important to note that when treating rare conditions such as Lennox-Gastaut syndrome and Dravet syndrome, a multi-drug approach is usually required.
To better understand how certain medications work, it is necessary to understand how the body interacts with a drug. There are four key steps that occur when a drug is administered. The first step is absorption, which determines the amount of drug that enters the bloodstream. For fat-soluble drugs, such as Epidiolex, absorption is generally lower than for water-soluble drugs, but can be increased when taken with fatty meals.
The second stage is distribution, which describes how a drug is spread throughout the body from the bloodstream to target tissues. Due to Epidiolex’s fat-soluble nature, it distributes to fatty regions more easily. However, the exact distribution behavior of this drug is still under investigation (O’Sullivan et al., 2024).
The next step is metabolism, which occurs primarily in the liver and gut. This process converts the active compound into inactive metabolites so it can be removed from the body. The final step is elimination, which refers to how the inactive drug is excreted. Epidiolex is eliminated primarily through feces and, to a lesser extent, through urine (FDA, 2018).
The specific mechanism of action of Epidiolex is still unknown; however, it has been shown to be effective in regulating neuronal excitability (Gray & Whalley, 2020).
The recommended dose is 2.5 mg/kg taken orally twice daily in solution form. After one week, the dose may be increased to 5 mg/kg twice daily. Patients who tolerate 10 mg/kg per day and require further dose adjustment may be increased to a maximum of 20 mg/kg per day. A 1 mL to 5 mL syringe is provided for accurate dosing, as household spoons are not suitable. Any remaining solution should be discarded 12 weeks after opening.
For patients with moderate to severe liver impairment, dose adjustments are recommended. Common side effects may include sleepiness, diarrhea, fatigue, decreased appetite, and suicidal ideation. If you are experiencing suicidal thoughts, contact your healthcare provider immediately. For a complete list of side effects, visit the official FDA website.
It is strongly recommended that Epidiolex be gradually withdrawn if discontinuation is advised and not stopped abruptly, as sudden withdrawal may lead to increased seizure frequency and potentially status epilepticus. Epidiolex is not recommended during pregnancy due to animal data suggesting potential fetal harm (FDA, 2018).
In conclusion, cannabidiol oral solution (Epidiolex) represents an important advancement in the treatment of rare and severe forms of epilepsy, particularly Lennox-Gastaut syndrome and Dravet syndrome. Although it is not considered a first-line therapy, evidence supports its effectiveness in reducing seizure frequency when used as part of a multi-drug treatment approach. Understanding its pharmacokinetic properties, dosing guidelines, and potential side effects is essential for safe and effective use. As research continues to explore its exact mechanism of action, Epidiolex remains a valuable therapeutic option for patients with treatment-resistant epilepsy when prescribed and monitored appropriately by a healthcare provider.
References:
Abu-Sawwa, R., Scutt, B., & Park, Y. (2020). Emerging use of Epidiolex (cannabidiol) in epilepsy. Journal of Pediatric Pharmacology and Therapeutics, 25(6), 485–499. https://doi.org/10.5863/1551-6776-25.6.485
Asadi-Pooya, A. A. (2018). Lennox-Gastaut syndrome: A comprehensive review. Neurological Sciences, 39, 403–414. https://doi.org/10.1007/s10072-017-3188-y
Dulac, O. (2001). Epileptic encephalopathy. Epilepsia, 42(Suppl. 3), 23–26. https://doi.org/10.1046/j.1528-1157.2001.042suppl.3023.x
Gray, R. A., & Whalley, B. J. (2020). The proposed mechanisms of action of CBD in epilepsy. Epileptic Disorders, 22(Suppl. 1), 10–15. https://doi.org/10.1684/epd.2020.1135
O’Sullivan, S. E., Jensen, S. S., Kolli, A. R., Nikolajsen, G. N., Bruun, H. Z., & Hoeng, J. (2024). Strategies to improve cannabidiol bioavailability and drug delivery. Pharmaceuticals, 17(2), 244. https://doi.org/10.3390/ph17020244
U.S. Food and Drug Administration. (2018). EPIDIOLEX (cannabidiol) oral solution: Highlights of prescribing information [PDF]. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf
