CBD reduces seizures through a remarkably wide range of mechanisms—including dampening neuroinflammation, modulating multiple receptor systems, and reducing oxidative stress—not just one single pathway.
Neuroscientists studying epilepsy mechanisms, neurologists wanting to understand why CBD works, and pharmaceutical researchers designing next-generation anti-seizure drugs.
What the researchers found
One of the challenges in understanding CBD's anti-seizure action is that it doesn't work through a single, clean mechanism the way most drugs do. This review maps the multiple pathways through which CBD appears to reduce seizures, with particular attention to neuroinflammation.
About one-third of epilepsy patients are resistant to conventional medications, many of which work through a single mechanism (usually enhancing GABA signaling). CBD's multi-target approach may explain why it helps some patients who don't respond to these drugs.
The neuroinflammation connection is especially interesting. Inflammation in the brain isn't just a consequence of seizures—it's now understood to be part of what causes them (epileptogenesis). CBD reduces neuroinflammation through immunomodulatory effects, potentially breaking the cycle where seizures cause inflammation which causes more seizures.
Beyond inflammation, CBD modulates the endocannabinoid system, adenosine receptors (involved in neural excitability), GPR55 receptors (recently linked to seizure activity), and TRPV1 channels (which regulate calcium signaling in neurons). It also reduces oxidative stress, which damages neurons and contributes to seizure susceptibility.
The FDA approved purified CBD (Epidiolex) in 2018 for Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. This review provides the mechanistic foundation for understanding why it works and why it might work for other neurological conditions too.
Why it matters
Understanding how CBD works—not just that it works—is crucial for two reasons. First, it guides which patients might respond best (those whose epilepsy involves neuroinflammation may be particularly good candidates). Second, it identifies targets for developing more potent or selective next-generation drugs that build on CBD's multi-mechanism approach.
The numbers in context
~33% of epilepsy patients are treatment-resistant. CBD modulates: endocannabinoid system, adenosine receptors, GPR55 receptors, TRPV1 channels. Epidiolex approved 2018 for LGS, Dravet, and TSC.
How the study worked
Narrative review focused on CBD's activity as a neuroinflammatory modulator and antiseizure agent. Synthesizes in vitro, in vivo, and clinical evidence on CBD's mechanisms of action in epilepsy. Covers endocannabinoid, adenosine, GPR55, TRPV1, and inflammatory pathways.
Who was studied
Review of existing studies on CBD and epilepsy.
What this study cannot tell us
Many mechanistic findings come from cell culture and animal models that may not fully translate to human epilepsy. The multi-target nature of CBD makes it difficult to determine which mechanisms are most clinically important. The review focuses on anti-seizure mechanisms but CBD may also have pro-seizure effects under some conditions. Narrative review format is subject to author selection bias.
How to read the evidence
Narrative review of preclinical and clinical mechanistic evidence—comprehensive but limited by the predominantly preclinical nature of mechanistic studies.
When this study was published
Published in 2025, synthesizing the latest research on CBD's anti-seizure mechanisms.
The bigger picture
This mechanistic review connects the basic science to clinical findings across multiple studies. RTHC-00189 showed 69% real-world response rates; RTHC-00186 provided prescribing guidance; RTHC-00160 created novel CBD analogues; and RTHC-00179 improved CBD delivery. This review explains the underlying biology that makes all of that work possible—and why CBD's multi-target approach may be fundamentally better suited to a multi-mechanism disorder like epilepsy.
Replication
Not stated in abstract.
Funding
Not reported in abstract.
Conflicts of interest
Not reported in abstract.
Questions still open
- Which of CBD's many mechanisms is most responsible for seizure reduction in humans? Could targeting neuroinflammation specifically (without CBD's other effects) be equally or more effective? Does the relative importance of different mechanisms vary across epilepsy syndromes?
Read the original research
Epilepsy, neuroinflammation and cannabidiol What do we know thus far?
Frontiers in pharmacology, 16, 1749260
Frontiers in Pharmacology is a reputable journal known for publishing high-quality research in pharmacology and related fields.
Citation
Pesántez Ríos, Gabriela; Perucca, Emilio; Striano, Pasquale; Caraballo, Roberto; Pesántez Ríos, Ximena; Pascual-Pascual, S I; Pesántez Cuesta, Galo. (2025). Epilepsy, neuroinflammation and cannabidiol What do we know thus far?. Frontiers in pharmacology, 16, 1749260. https://doi.org/10.3389/fphar.2025.1749260
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