Final analysis of potential drug–drug interactions between highly purified cannabidiol and anti‐seizure medications in an open‐label expanded access program

OBJECTIVE: The aim of this study was to assess potential drug–drug interactions between highly purified cannabidiol (CBD) and anti‐seizure medications (ASMs). METHODS: Our group previously reported that in a sample of adults and children receiving CBD in an open‐label expanded access program, there were several ASMs noted to increase in serum levels with increasing doses of CBD. We analyzed if an increased number of observations over time resulted in changes in potential interactions and if potential interactions were associated with time since enrollment, demographics, or the overall rating of adverse effects. RESULTS: In 169 participants (80 adults), with increasing weight‐based CBD dose, there were associated increases in serum levels of clobazam and N‐desmethylclobazam, free valproate, felbamate, and topiramate in the adult and pediatric arms combined, levetiracetam in the pediatric arm only, and permapanel in the adult arm only. There were no associations noted in these level changes with time since enrollment, biological sex, and adverse events profile scores. SIGNIFICANCE: This study confirms some previously identified interactions with CBD and identifies other potential pharmacokinetic interactions; however, the clinical significance of these observations is likely minor, and there is no effect of time on these findings.