The first plant-derived, purified pharmaceutical-grade cannabidiol (CBD) medication, Epidiolex, was approved in the United States by the FDA on June 25, 2018. Its approval for patients ≥ 2 years of age with Dravet syndrome (DS) or Lennox-Gastaut syndrome (LGS) markedly altered the treatment of medically refractory seizures in these disorders. This state-of-the-art review will discuss the history of CBD, its current pharmacology and toxicology, evidence supporting its use in a variety of epileptic syndromes, common side effects and adverse effects, and pharmacokinetically based drug-drug interactions. Owing to the importance in considering side effects, adverse effects, and drug-drug interactions in patients with medically refractory epilepsy syndromes, this review will take a deeper look into the nuances of the above within a clinical context, as compared to the other antiepileptic medications. Furthermore, despite the limited data regarding clinically significant drug-drug interactions, potential pharmacokinetic drug-drug interactions with CBD and other antiepileptics are theorized on the basis of their metabolic pathways. The article will further elucidate future research in terms of long-term efficacy, safety, and drug interactions that is critical to addressing unanswered questions relevant to clinical practice.

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