Evidence map›Paper›PMID 29540584›Full record

Trial reportNeurology2018

Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome.

Orrin Devinsky, Anup D Patel, Elizabeth A Thiele, Matthew H Wong, Richard Appleton, Cynthia L Harden, Sam Greenwood, Gilmour Morrison, Kenneth Sommerville, GWPCARE1 Part A Study Group

2 registry-linked trialsOpen access · hybridAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 210 papers, 25 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
210citing papers in PubMed, 25 pooled it
37.5field-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.

NCT02091206 phase2completednot on this map

A Double Blind, Placebo-controlled, Two-part Study to Investigate the Dose-ranging Safety and Pharmacokinetics, Followed by the Efficacy and Safety of Cannabidiol (GWP42003-P) in Children and Young Adults With Dravet Syndrome

TypeinterventionalSponsorJazz PharmaceuticalsRan2014 to 2015Enrolled34ConditionsEpilepsy, Dravet SyndromeArmsGWP42003-P 5 mg/kg/day Dose, Placebo control, GWP42003-P 10 mg/kg/day Dose, GWP42003-P 20 mg/kg/day Dose
NCT04280289 early_phase1completednot on this mapstarted 2021, after this paper: background citation

CBD Cannabis Extract: Pharmacokinetic Studies

TypeinterventionalSponsorUniversity of Mississippi, OxfordRan2021 to 2021Enrolled10ConditionsEpilepsyArmscannabidiol extract
3 · Its place in the literature

Who cites it

210 citing papers in PubMed, 25 syntheses or guidelines pooled it, 443 citations in OpenAlex.

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150 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 2 countries.

Orrin DevinskyFrom the NYU Comprehensive Epilepsy Center (O.D.), New York, NY;Nationwide Children's Hospital and the Ohio State University College of Medicine (A.D.P.), Columbus; Massachusetts General Hospital (E.A.T.), Boston; Wake Forest School of Medicine (M.H.W.), Winston-Salem, NC; Alder Hey Children's Health Park (R.A.), Liverpool, UK; Mount Sinai Health System (C.L.H.), New York, NY; GW Research Ltd. (S.G., G.M.), Cambridge, UK; and Greenwich Biosciences (K.S.), Carlsbad, CA. Od4@nyu.edu.
Anup D PatelFrom the NYU Comprehensive Epilepsy Center (O.D.), New York, NY;Nationwide Children's Hospital and the Ohio State University College of Medicine (A.D.P.), Columbus; Massachusetts General Hospital (E.A.T.), Boston; Wake Forest School of Medicine (M.H.W.), Winston-Salem, NC; Alder Hey Children's Health Park (R.A.), Liverpool, UK; Mount Sinai Health System (C.L.H.), New York, NY; GW Research Ltd. (S.G., G.M.), Cambridge, UK; and Greenwich Biosciences (K.S.), Carlsbad, CA.
Elizabeth A ThieleFrom the NYU Comprehensive Epilepsy Center (O.D.), New York, NY;Nationwide Children's Hospital and the Ohio State University College of Medicine (A.D.P.), Columbus; Massachusetts General Hospital (E.A.T.), Boston; Wake Forest School of Medicine (M.H.W.), Winston-Salem, NC; Alder Hey Children's Health Park (R.A.), Liverpool, UK; Mount Sinai Health System (C.L.H.), New York, NY; GW Research Ltd. (S.G., G.M.), Cambridge, UK; and Greenwich Biosciences (K.S.), Carlsbad, CA.
Matthew H WongFrom the NYU Comprehensive Epilepsy Center (O.D.), New York, NY;Nationwide Children's Hospital and the Ohio State University College of Medicine (A.D.P.), Columbus; Massachusetts General Hospital (E.A.T.), Boston; Wake Forest School of Medicine (M.H.W.), Winston-Salem, NC; Alder Hey Children's Health Park (R.A.), Liverpool, UK; Mount Sinai Health System (C.L.H.), New York, NY; GW Research Ltd. (S.G., G.M.), Cambridge, UK; and Greenwich Biosciences (K.S.), Carlsbad, CA.
Richard AppletonFrom the NYU Comprehensive Epilepsy Center (O.D.), New York, NY;Nationwide Children's Hospital and the Ohio State University College of Medicine (A.D.P.), Columbus; Massachusetts General Hospital (E.A.T.), Boston; Wake Forest School of Medicine (M.H.W.), Winston-Salem, NC; Alder Hey Children's Health Park (R.A.), Liverpool, UK; Mount Sinai Health System (C.L.H.), New York, NY; GW Research Ltd. (S.G., G.M.), Cambridge, UK; and Greenwich Biosciences (K.S.), Carlsbad, CA.
Cynthia L HardenFrom the NYU Comprehensive Epilepsy Center (O.D.), New York, NY;Nationwide Children's Hospital and the Ohio State University College of Medicine (A.D.P.), Columbus; Massachusetts General Hospital (E.A.T.), Boston; Wake Forest School of Medicine (M.H.W.), Winston-Salem, NC; Alder Hey Children's Health Park (R.A.), Liverpool, UK; Mount Sinai Health System (C.L.H.), New York, NY; GW Research Ltd. (S.G., G.M.), Cambridge, UK; and Greenwich Biosciences (K.S.), Carlsbad, CA.
Sam GreenwoodFrom the NYU Comprehensive Epilepsy Center (O.D.), New York, NY;Nationwide Children's Hospital and the Ohio State University College of Medicine (A.D.P.), Columbus; Massachusetts General Hospital (E.A.T.), Boston; Wake Forest School of Medicine (M.H.W.), Winston-Salem, NC; Alder Hey Children's Health Park (R.A.), Liverpool, UK; Mount Sinai Health System (C.L.H.), New York, NY; GW Research Ltd. (S.G., G.M.), Cambridge, UK; and Greenwich Biosciences (K.S.), Carlsbad, CA.
Gilmour MorrisonFrom the NYU Comprehensive Epilepsy Center (O.D.), New York, NY;Nationwide Children's Hospital and the Ohio State University College of Medicine (A.D.P.), Columbus; Massachusetts General Hospital (E.A.T.), Boston; Wake Forest School of Medicine (M.H.W.), Winston-Salem, NC; Alder Hey Children's Health Park (R.A.), Liverpool, UK; Mount Sinai Health System (C.L.H.), New York, NY; GW Research Ltd. (S.G., G.M.), Cambridge, UK; and Greenwich Biosciences (K.S.), Carlsbad, CA.
Kenneth SommervilleFrom the NYU Comprehensive Epilepsy Center (O.D.), New York, NY;Nationwide Children's Hospital and the Ohio State University College of Medicine (A.D.P.), Columbus; Massachusetts General Hospital (E.A.T.), Boston; Wake Forest School of Medicine (M.H.W.), Winston-Salem, NC; Alder Hey Children's Health Park (R.A.), Liverpool, UK; Mount Sinai Health System (C.L.H.), New York, NY; GW Research Ltd. (S.G., G.M.), Cambridge, UK; and Greenwich Biosciences (K.S.), Carlsbad, CA.
GWPCARE1 Part A Study Group
Nationwide Children's Hospital · US

Funding

Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
NCATS NIH HHS UL1 TR001420
6 · The paper itself

Abstract

objectiveTo evaluate the safety and preliminary pharmacokinetics of a pharmaceutical formulation of purified cannabidiol (CBD) in children with Dravet syndrome.

methodsPatients aged 4-10 years were randomized 4:1 to CBD (5, 10, or 20 mg/kg/d) or placebo taken twice daily. The double-blind trial comprised 4-week baseline, 3-week treatment (including titration), 10-day taper, and 4-week follow-up periods. Completers could continue in an open-label extension. Multiple pharmacokinetic blood samples were taken on the first day of dosing and at end of treatment for measurement of CBD, its metabolites 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, and antiepileptic drugs (AEDs; clobazam and metabolite

resultsThirty-four patients were randomized (10, 8, and 9 to the 5, 10, and 20 mg/kg/d CBD groups, and 7 to placebo); 32 (94%) completed treatment. Exposure to CBD and its metabolites was dose-proportional (AUC

conclusionsExposure to CBD and its metabolites increased proportionally with dose. An interaction with N-CLB was observed, likely related to CBD inhibition of cytochrome P450 subtype 2C19. CBD resulted in more AEs than placebo but was generally well-tolerated. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for children with Dravet syndrome, CBD resulted in more AEs than placebo but was generally well-tolerated.

Indexed as

AnticonvulsantsBenzodiazepinesCannabidiolChildChild, PreschoolClobazamDose-Response Relationship, DrugDouble-Blind MethodDrug Therapy, CombinationEpilepsies, MyoclonicFollow-Up StudiesHumansTreatment OutcomeAnticonvulsantsBenzodiazepinesCannabidiolClobazamN-desmethylclobazam

Identifiers

PMID29540584
PMCPMC5890607
OpenAlexW2791384105

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.