CBD shows promise for severe epilepsy but faces challenges with drug interactions and inconsistent absorption

What the researchers found

The authors reviewed the rapidly evolving field of cannabinoids for epilepsy, noting several important developments and remaining challenges.

Recent randomized placebo-controlled trials confirmed CBD's efficacy in two severe childhood epilepsy syndromes: Dravet syndrome and Lennox-Gastaut syndrome. This represented a major advance from the earlier era of anecdotal reports.

However, the review highlighted significant practical challenges. Cannabinoids appear to work through mechanisms other than the endogenous cannabinoid receptors CB1 and CB2, and the exact mechanism of antiseizure activity remains unclear. The pharmacokinetics are complex, with variable bioavailability making it difficult to develop consistent oral formulations.

Drug interactions represent a major complication for everyday use, particularly since epilepsy patients typically take multiple antiseizure medications. The review noted that further placebo-controlled studies were underway testing cannabidivarin (CBDV) in adults with focal epilepsy, potentially expanding the range of epilepsy types that might respond to cannabinoid treatment.

Why it matters

As CBD-based epilepsy treatments move from clinical trials to clinical practice, understanding the practical challenges is crucial for patients and clinicians. The drug interaction profile is particularly important because poorly managed interactions could paradoxically worsen seizure control or cause toxicity from co-administered medications.

The numbers in context

Randomized trials confirmed efficacy in Dravet and Lennox-Gastaut syndromes. Cannabidivarin trials underway for adult focal epilepsy. Two endogenous cannabinoid receptors (CB1, CB2) do not appear to mediate the antiseizure effect.

How the study worked

This was a narrative review of the current state of cannabinoid research in epilepsy, covering mechanisms of action, pharmacokinetics, clinical trial evidence, drug interactions, and ongoing research.

What this study cannot tell us

This is a brief narrative review rather than a systematic review. The evidence at the time was strongest for two severe childhood epilepsies, and generalizability to other epilepsy types was uncertain. Drug interaction data were still accumulating. Long-term safety data were limited.

How to read the evidence

This review covers evidence from randomized controlled trials for specific syndromes, providing moderate overall evidence across the epilepsy field.

When this study was published

Published in 2018, around the time of Epidiolex FDA approval. Clinical experience with CBD in epilepsy has expanded significantly since.

The bigger picture

The cannabinoid-epilepsy story represents one of the most successful translations from patient advocacy and anecdotal evidence to rigorous clinical trials and FDA approval. The remaining challenges, especially around drug interactions and mechanisms of action, are now the focus of the next phase of research.

Questions still open

• How exactly does CBD prevent seizures if not through cannabinoid receptors? Can the drug interaction challenges be managed well enough for routine clinical use? Will cannabidivarin prove effective for the much larger population of adults with focal epilepsy?

Common questions

Read the original research

Cannabinoids for epilepsy: What do we know and where do we go?

Epilepsia, 59(2), 291-296

Citation

Brodie, Martin J; Ben-Menachem, Elinor. (2018). Cannabinoids for epilepsy: What do we know and where do we go?. Epilepsia, 59(2), 291-296. https://doi.org/10.1111/epi.13973

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