Interaction of cannabidiol with other antiseizure medications: A narrative review

Abstract

Cannabidiol is efficacious as an adjunctive treatment in children with epilepsy associated with Dravet and Lennox-Gastaut syndromes. As its role is currently adjunctive, we reviewed the interactions of cannabidiol with other antiseizure medications (ASMs). Methods: A search of Cochrane, Pubmed and Embase databases from January 2015 to April 2020 was performed. All original research papers discussing interactions between cannabidiol and ASMs were included. Bibliographies of review articles were searched to identify further papers. Adverse events and side effects were excluded. Results: Cannabidiol interacts with ASMs through both pharmacokinetic and pharmacodynamic mechanisms. Thirty studies were identified (eighteen observational cohort studies, two randomised-control trials, three case reports/series, three animal studies, two briefing reports, an analysis of cohort data and a clinical trial simulation). There is potential for pharmacokinetic interactions between CBD and brivaracetam, clobazam, eslicarbazepine, lacosamide, gabapentin, oxcarbazepine, phenobarbital, potassium bromide, pregabalin, rufinamide, sirolimus/everolimus, stiripentol, tiagabine, topiramate and zonisamide. Pharmacodynamic interactions were identified for clobazam, valproate and levetiracetam. An animal study identified that the brain concentration of ASMs may be altered while the serum concentration remains the same. Conclusion: Pharmacokinetic and pharmacodynamic interactions exist between cannabidiol and ASMs. The cytochrome p450 system in particular has been implicated in pharmacokinetic interactions, although not exclusively. The existing literature is limited for some ASMs by studies having relatively small cohorts. As increasing numbers of patients use cannabidiol, specialists need to monitor closely for interactions clinically and with blood levels when required.

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

“…However, no comparative effectiveness data exist to recommend specific antiseizure medications, everolimus, or cannabidiol over one another in a particular patient. Clinicians should be aware that both everolimus 107 and cannabidiol 108 have important drug interactions with other antiseizure medications, including with each other. 109,110 Dietary interventions, including a ketogenic diet 111,112 or low-glycemic index treatment, 113 may be an effective nonpharmacological therapy for patients with TSC with intractable epilepsy, including infantile spasms refractory to vigabatrin and hormonal therapies.…”

Effects of chronic cannabidiol in a mouse model of naturally occurring neuroinflammation, neurodegeneration, and spontaneous seizures

“…The copyright holder for this preprint this version posted March 8, 2022. ; https://doi.org/10.1101/2022.03.07.483344 doi: bioRxiv preprint It has been reported that CBD can increase the concentration of active metabolites of other antiseizure medications. The most robust evidence comes from CBD-clobazam interactions 36 .…”

“…It has been reported that CBD can increase the concentration of active metabolites of other antiseizure medications. The most robust evidence comes from CBD-clobazam interactions 36 .…”

Pharmacokinetic Drug–Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients

“…ESL reduces concentration of simvastatin and rosuvastatin by 54% and up to 39%, respectively [29,99,100]. CBD significantly increase levels of ESL in serum [23,25].…”