CBD interacts with at least 15 anti-seizure medications through multiple mechanisms | Research

The takeaway

A review of 30 studies found cannabidiol has pharmacokinetic interactions with at least 15 anti-seizure medications (including clobazam, valproate, and topiramate) and pharmacodynamic interactions with three, primarily through the cytochrome P450 system.

Neurologists prescribing CBD, pharmacists, epilepsy care teams

CBD has pharmacokinetic interactions with at least 15 anti-seizure medications

What the researchers found

CBD has potential pharmacokinetic interactions with 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. Animal data suggested brain drug concentrations may change while serum levels remain stable.

Why it matters

Since CBD is used adjunctively with other anti-seizure medications, understanding interactions is essential for safe prescribing. The finding that brain levels may change without serum level changes is particularly concerning for therapeutic drug monitoring.

The numbers in context

30 studies identified; pharmacokinetic interactions with 15 ASMs; pharmacodynamic interactions with 3 ASMs; cytochrome P450 primarily implicated; animal data showed brain-serum concentration discordance

How the study worked

Narrative review of 30 studies (18 observational cohort, 2 RCTs, 3 case reports/series, 3 animal studies, 2 briefing reports, 1 cohort analysis, 1 clinical trial simulation) on CBD interactions with anti-seizure medications, identified through Cochrane, PubMed, and Embase searches (2015-2020).

What this study cannot tell us

Some interactions based on small cohorts or case reports. Narrative rather than systematic review. Drug interactions may vary with CBD dose, formulation, and individual patient metabolism. Animal brain-serum discordance finding needs human confirmation.

How to read the evidence

Comprehensive review of 30 studies covering multiple interaction mechanisms, though some interactions are based on limited evidence.

When this study was published

Published in 2021 reviewing studies from 2015-2020.

The bigger picture

The breadth of CBD's drug interaction profile underscores that it is not a "gentle" supplement but a pharmacologically active compound requiring the same careful drug interaction management as any potent medication.

Questions still open

Are clinicians adequately monitoring for CBD drug interactions in practice? How should therapeutic drug monitoring be modified when brain and serum levels may diverge?

Common questions

Which drug interactions are most concerning?

The clobazam interaction is the most clinically significant, as CBD raises levels of N-desmethylclobazam. Valproate interactions can cause liver enzyme elevations. The finding that brain drug levels may change without serum changes is also concerning for any co-prescribed medication.

Why does CBD interact with so many drugs?

CBD is metabolized by and inhibits multiple cytochrome P450 enzymes, which are the same enzymes that process many anti-seizure medications. This creates a broad interaction potential that requires careful monitoring when CBD is added to existing medication regimens.

Read the original research

Interaction of cannabidiol with other antiseizure medications: A narrative review.

Seizure, 86, 189-196

View on PubMed ↗Publisher’s paper ↗

Citation

Gilmartin, Christopher G S; Dowd, Zoya; Parker, Alasdair P J; Harijan, Pooja. (2021). Interaction of cannabidiol with other antiseizure medications: A narrative review.. Seizure, 86, 189-196. https://doi.org/10.1016/j.seizure.2020.09.010