Epidiolex ® (Cannabidiol- CBD) is approved for epilepsy associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients over 2 years of age. Common side effects include somnolence and diarrhea. Recent studies have demonstrated interactions between cannabidiol and several other antiseizure medications. However, little is known regarding interactions between cannabidiol and other classes of medications. We discuss an autistic patient with LGS and significant psychiatric comorbidities who was being treated with multiple antiseizure and psychiatric medications, including lithium, when CBD was added to his medical regimen. Several weeks after initiating CBD therapy, he developed hypersomnolence, ataxia and decreased oral intake and was found to have lithium toxicity. Lithium was discontinued and his symptoms resolved. He remains on CBD and 2 other antiseizure medications, seizure-free with improved behavior. We review mechanisms of action and pharmacokinetics of CBD and discuss possible explanations for lithium toxicity in this patient.
Conflict of interest statement
© The Author(s) 2020.
Keywords: antiepileptic drugs; antiseizure drugs; autism; behavior; epilepsy; pediatric.
Products containing cannabidiol (CBD) seem to be all the rage these days, promising relief from a wide range of maladies, from insomnia and hot flashes to chronic pain and seizures. Some of these claims have merit to them, while some of them are just hype. But it won’t hurt to try, right? Well, not so fast. CBD is a biologically active compound, and as such, it may also have unintended consequences. These include known side effects of CBD, but also unintended interactions with supplements, herbal products, and over-the-counter (OTC) and prescription medications.
Doubling up on side effects
The researchers further warned that while the list may be used as a starting point to identify potential drug interactions with marijuana or CBD oil, plant-derived cannabinoid products may deliver highly variable cannabinoid concentrations (unlike the FDA-regulated prescription cannabinoid medications previously mentioned), and may contain many other compounds that can increase the risk of unintended drug interactions.
Does the form of CBD matter?
Researchers from Penn State College of Medicine evaluated existing information on five prescription CBD and delta-9-tetrahydrocannabinol (THC) cannabinoid medications: antinausea medications used during cancer treatment (Marinol, Syndros, Cesamet); a medication used primarily for muscle spasms in multiple sclerosis (Sativex, which is not currently available in the US, but available in other countries); and an antiseizure medication (Epidiolex). Overall, the researchers identified 139 medications that may be affected by cannabinoids. This list was further narrowed to 57 medications, for which altered concentration can be dangerous. The list contains a variety of drugs from heart medications to antibiotics, although not all the drugs on the list may be affected by CBD-only products (some are only affected by THC). Potentially serious drug interactions with CBD included
He met criteria for Autism Spectrum Disorder, co-morbid with severe intellectual disability and associated aggressive and self-harmful behaviors and sleep difficulties. At baseline, he was non-verbal with incontinence, though with full strength and ambulation.
Cannabidiol has a bidirectional drug–drug interaction with clobazam. It inhibits cytochrome P450 (CYP)2C19 and increases levels of the nordesmethyl metabolite of clobazam, which has biologic activity. 14 Conversely, clobazam increases levels of CBD’s metabolite, 7-hydroxy-CBD. Adult and pediatric studies have demonstrated increased clobazam and N-desmethylclobazam (active metabolite of clobazam) in response to increasing doses of CBD. 15
Since its approval by the FDA, additional studies have shown interactions between CBD and other antiseizure medications. 7 However, little is known regarding interactions between CBD and other classes of medications.
Interactions With Other Anti-Seizure Medications
Lithium is an efficacious and FDA-approved treatment for mood disorders including mania, acute depression, and unipolar depressive disorder. However, lithium has a narrow therapeutic index. Thus, clinical monitoring along with serum concentration monitoring is imperative. Lithium is not protein bound, not metabolized, has a bioavailability of 80-100%, and is renally eliminated. Side effects associated with elevated lithium levels include vomiting, diarrhea, coarse hand tremor, sluggishness, dysarthria, hyperreflexia, and oliguria. These side effects greatly increase in frequency and severity when lithium blood levels exceed 1.5 mEq/L. Severe lithium toxicity can lead to impaired consciousness, seizures, coma, and death. 18