Cannabidiol is an orally available cannabinoid that is used to treat patients with refractory epilepsy due to Lennox-Gastaut or Dravet syndrome. Cannabidiol is associated with frequent serum enzyme elevations during therapy particularly with higher doses but has not been linked to cases of clinically apparent liver injury with jaundice.
In prelicensure studies, serum aminotransferase elevations arose during cannabidiol therapy in 34% to 47% of patients compared to 18% of controls who were receiving other anticonvulsant medications. Elevations above 3 times ULN occurred in 13% of cannabidiol treated compared to 1% on placebo. ALT and AST elevations were more frequent with higher doses and were particularly common (and sometimes delayed) in patients who were receiving valproate and clobazam. The aminotransferase elevations typically arose within the first two months of treatment and were transient, mild-to-moderate in severity, and not associated with symptoms or jaundice. There have been no convincing reports of clinically apparent liver injury with jaundice attributable to cannabidiol, but it has had very limited general use.
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Cannabidiol (kan” a bi dye’ ol) is a natural cannabinoid, the second most common component in Cannabis sativa. Unlike the most abundant cannabinoid delta-9-tetrahydrocannabinol (THC), the psychoactive ingredient of marijuana, cannabidiol has minimal psychoactive properties and actually decreases the risk of psychotic symptoms and impaired cognition after cannabis use. The mechanism of action of cannabidiol is unknown, but it may be a partial agonist of cannabinoid receptors. Cannabidiol was found to improve symptoms in schizophrenia and to reduce the frequency of seizures in treatment-resistant epilepsy, particularly in those with Lennox-Gastaut or Dravet syndrome, two rare but severe childhood-onset forms of epilepsy. Cannabidiol was approved for use in the United States in 2018. Current indications are limited to treatment of seizures associated with Lennox-Gastaut or Dravet syndrome in adults and in children above the age of two. Cannabidiol is available as an oral solution of 100 mg/mL under the brand name Epidiolex. The typical dose is 2.5 mg/kg twice daily, which can be increased based upon tolerance and effect to 5 mg/kg twice daily and to a maximum of 10 mg/kg twice daily. The dose should be reduced in patients with pre-existing hepatic impairment. Side effects are mostly dose related and can include fatigue, somnolence, dizziness, sleep disturbance, insomnia, anorexia, weight loss, diarrhea, infections and rash. Rare, but potentially severe side effects include marked sedation and somnolence, suicidal behavior and ideation and hypersensitivity reactions. Cannabidiol is generally used in combination with other anticonvulsants and is prone to drug-drug interactions that may affect drug levels and side effects of those agents, particularly valproate and clobazam.
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.
In studies, these were more common in the first two weeks on Epidiolex, after which time they tended to diminish. Additionally, many of the studies on the drug involved at least one other anti-seizure drug as well, so the side effects may not all have been due to Epidiolex.
When used with other anti-seizure drugs, CBD can cause elevated liver enzymes, which is often a sign of liver injury.
In the aforementioned 2019 review of studies on this drug, however, researchers found that while adding Epidiolex to a treatment regimen may increase certain specific side effects, it may actually decrease the overall amount of side effects participants experienced.
LGS is a developmental disorder that begins in early childhood and is characterized by multiple seizure types, as well as physical and cognitive deficits. The seizures of LGS are difficult to control and are managed with a different medication regimen than that which is used for most epilepsy types.
Dravet syndrome is a developmental disorder that begins in early childhood and is associated with multiple seizure types as well as seizures triggered by fevers. People with Dravet syndrome often have behavioral challenges and learning difficulties.
At this time, cannabidiol has been proven effective for only a few medical conditions. Due to the side effects, it is recommended to be used with caution.
It is not completely clear why CBD can reduce some types of seizures. It is known to have a range of biochemical effects on nerve cells in the brain, some of which may have an impact on seizures. Medical research on CBD is still in its early stages.