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

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.

Gilmartin, Christopher G S et al.·Seizure·2021·Moderate EvidenceNarrative Review
RTHC-03154Narrative ReviewModerate Evidence2021RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Narrative Review
Evidence
Moderate Evidence
Sample
Not reported

What This Study 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.

Key Numbers

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 They Did This

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).

Why This Research 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 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.

What This Study Doesn't 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.

Questions This Raises

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

Trust & Context

Key Stat:
CBD has pharmacokinetic interactions with at least 15 anti-seizure medications
Evidence Grade:
Comprehensive review of 30 studies covering multiple interaction mechanisms, though some interactions are based on limited evidence.
Study Age:
Published in 2021 reviewing studies from 2015-2020.
Original Title:
Interaction of cannabidiol with other antiseizure medications: A narrative review.
Published In:
Seizure, 86, 189-196 (2021)
Database ID:
RTHC-03154

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study

Summarizes existing research without a strict systematic method.

What do these levels mean? →

Frequently Asked 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 More on RethinkTHC

Cite This Study

RTHC-03154·https://rethinkthc.com/research/RTHC-03154

APA

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

MLA

Gilmartin, Christopher G S, et al. "Interaction of cannabidiol with other antiseizure medications: A narrative review.." Seizure, 2021. https://doi.org/10.1016/j.seizure.2020.09.010

RethinkTHC

RethinkTHC Research Database. "Interaction of cannabidiol with other antiseizure medication..." RTHC-03154. Retrieved from https://rethinkthc.com/research/gilmartin-2021-interaction-of-cannabidiol-with

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.