Evidence map›Paper›PMID 31625159›Full record

ArticleEpilepsia2019

Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions.

Lyndsey L Anderson, Nathan L Absalom, Sarah V Abelev, Ivan K Low, Peter T Doohan, Lewis J Martin, Mary Chebib, Iain S McGregor, Jonathon C Arnold

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 4 pooled it
13.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 4 syntheses or guidelines pooled it, 154 citations in OpenAlex.

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  19. Research and Clinical Practice Involving the Use ofPharmaceuticals (Basel, Switzerland) · 2024
    Review
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7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Lyndsey L AndersonBrain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-0037-0891
Nathan L AbsalomLambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia.
Sarah V AbelevDiscipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Ivan K LowLambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia.
Peter T DoohanDiscipline of Pharmacology, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Lewis J MartinBrain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
Mary ChebibBrain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
Iain S McGregorBrain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
Jonathon C ArnoldBrain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
The University of Sydney · AU

Funding

Australian National Health and Medical Research CouncilLambert Initiative for Cannabinoid Therapeutics
6 · The paper itself

Abstract

objectiveCannabidiol (CBD) has been approved by the US Food and Drug Administration (FDA) to treat intractable childhood epilepsies, such as Dravet syndrome and Lennox-Gastaut syndrome. However, the intrinsic anticonvulsant activity of CBD has been questioned due to a pharmacokinetic interaction between CBD and a first-line medication, clobazam. This recognized interaction has led to speculation that the anticonvulsant efficacy of CBD may simply reflect CBD augmenting clobazam exposure. The present study aimed to address the nature of the interaction between CBD and clobazam.

methodsWe examined whether CBD inhibits human CYP3A4 and CYP2C19 mediated metabolism of clobazam and N-desmethylclobazam (N-CLB), respectively, and performed studies assessing the effects of CBD on brain and plasma pharmacokinetics of clobazam in mice. We then used the Scn1a

resultsCBD potently inhibited CYP3A4 mediated metabolism of clobazam and CYP2C19 mediated metabolism of N-CLB. Combination CBD-clobazam treatment resulted in greater anticonvulsant efficacy in Scn1a SIGNIFICANCE: Our study highlights the involvement of both pharmacodynamic and pharmacokinetic interactions between CBD and clobazam that may contribute to its efficacy in Dravet syndrome.

Indexed as

AnimalsAnticonvulsantsCannabidiolClobazamDose-Response Relationship, DrugDrug Evaluation, PreclinicalDrug InteractionsDrug Therapy, CombinationEpilepsies, MyoclonicHumansMiceMice, TransgenicNAV1.1 Voltage-Gated Sodium ChannelAnticonvulsantsCannabidiolClobazamNAV1.1 Voltage-Gated Sodium ChannelScn1a protein, mousecannabidiolcannabisclobazamDravet syndromeepilepsy

Identifiers

PMID31625159
PMCPMC6900043
OpenAlexW2980764484

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.