Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome
Open accessAbstract
BACKGROUND: The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period. RESULTS: The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, -22.8 percentage points; 95% confidence interval [CI], -41.1 to -5.4; P=0.01). The percentage of patients who had at least a 50% reduction in convulsive-seizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P=0.08). The patient's overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P=0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P=0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P=0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group. CONCLUSIONS: Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375 .).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A phase 2 RCT of soticlestat in patients with Dravet syndrome showed a significant placebo-adjusted median reduction in convulsive seizure frequency of 46% over the full treatment period, whereas reduction in drop seizures in those with LGS was not significant.
“A phase 2 RCT of soticlestat in patients with Dravet syndrome showed a significant placebo-adjusted median reduction in convulsive seizure frequency of 46% over the full treatment period, whereas reduction in drop seizures in those with LGS was not significant 188,191 .”
From Developmental and epileptic encephalopathies (2024) · cites this paper as [188]
Split into 2 atoms — 0 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredRandomised placebo-controlled trials (RCTs) of cannabidiol demonstrated efficacy in Dravet syndrome, LGS and TSC, with significant median percent reductions in target seizures compared with placebo of 38.9%, 41.9% and 48.6%.
“Randomised placebo-controlled trials (RCTs) of cannabidiol demonstrated efficacy in Dravet syndrome, LGS and TSC, with significant median percent reductions in target seizures compared with placebo of 38.9% 188 , 41.9% 189 and 48.6% 190 .”
From Developmental and epileptic encephalopathies (2024) · cites this paper as [188]
Open-blind and double-blind controlled clinical trials confirmed and expanded preliminary findings on the efficacy, security and tolerability of CBD in children and adolescents with treatment-resistant epilepsy, particularly Dravet and Lennox-Gastaut syndromes.
“More recently, open-blind and double-blind, controlled clinical trials investigated the efficacy, security and tolerability of CBD in children and adolescents with treatment-resistant epilepsy (particularly Dravet and Lennox-Gastaut syndromes) confirmed and expanded these preliminary findings (137–140).”
From Translational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age (2018) · cites this paper as [138]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Kwan, P., Arzimanoglou, A. A., Berg, A. T., Brodie, M. J., Hauser, W. A., Mathern, G. W., Moshé, S. L., Perucca, E., Wiebe, S., & French, J. A. (2009) · Epilepsia · doi:10.1111/j.1528-1167.2009.02397.x · Cited by 4,918 · see citing works
Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial
Devinsky, O., Marsh, E., Friedman, D., Thiele, E., Laux, L., Sullivan, J., Miller, I., Flamini, R., Wilfong, A., Filloux, F., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00379-8 · Cited by 900 · see citing works
Self-citationChronic Administration of Cannabidiol to Healthy Volunteers and Epileptic Patients
Cunha, J. M., Carlini, E. A., Pereira, A. E., Ramos, O. L., Pimentel, C., Gagliardi, R. J., Sanvito, W. L., Lander, N., & Mechoulam, R. (2008) · Pharmacology · doi:10.1159/000137430 · Cited by 570 · see citing works
Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsy
Geffrey, A. L., Pollack, S. F., Bruno, P. L., & Thiele, E. A. (2015) · Epilepsia · doi:10.1111/epi.13060 · Cited by 496 · see citing works
Self-citationPorter, B. E., & Jacobson, C. A. (2013) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2013.08.037 · Cited by 359 · see citing works
Cannabidiol Displays Antiepileptiform and Antiseizure Properties In Vitro and In Vivo
Jones, N. A., Hill, A. J., Smith, I., Bevan, S. A., Williams, C. M., Whalley, B. J., & Stephens, G. J. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.159145 · Cited by 347 · see citing works
Sudden, Unexpected Death in Epilepsy
Devinsky, O. (2011) · New England Journal of Medicine · doi:10.1056/nejmra1010481 · Cited by 336 · see citing works
Self-citationCooper, M. S., McIntosh, A. M., Crompton, D. E., McMahon, J. M., Schneider, A., Farrell, K., Ganesan, V., Gill, D. S., Kivity, S., Lerman‐Sagie, T., et al. (2016) · Epilepsy Research · doi:10.1016/j.eplepsyres.2016.10.006 · Cited by 320 · see citing works
Self-citationToward drugs derived from cannabis
Mechoulam, R., & Carlini, E. A. (1978) · Die Naturwissenschaften · doi:10.1007/bf00450585 · Cited by 140 · see citing works
Anticonvulsant effect of cannabidiol.
Fr, A., & Cridland, S. (1986) · PubMed · Cited by 81 · see citing works
Zadeh, W. W., Escartín, A., Byrnes, W., Tennigkeit, F., Borghs, S., Li, T., Dedeken, P., & Backer, M. D. (2015) · Seizure · doi:10.1016/j.seizure.2015.07.001 · Cited by 51 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Trembly B, Sherman M. Double-blind clinical study of cannabidiol as a second- ary anticonvulsant. Presented at the Mari- juana '90 International Conference on Cannabis and Cannabinoids, Kolympari, Crete, July 8-11, 1990.
- Statistical review and evaluation: anti- epileptic drugs and suicidality. Silver Spring, MD: Food and Drug Administra- tion, 2008 (http://www .fda .gov/ downloads/ drugs/ drugsafety/ postmarketdrugsafety informationforpatientsandproviders/ ucm192556 .pdf).
Cited by
Sorted by citations
Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome
Devinsky, O., Patel, A. D., Cross, J. H., Villanueva, V., Wirrell, E. C., Privitera, M., Greenwood, S. M., Roberts, C., Checketts, D., VanLandingham, K. E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1714631 · Cited by 1,015 · see citing works
Self-citationCannabinoids and the expanded endocannabinoid system in neurological disorders
Cristino, L., Bisogno, T., & Di Marzo, V. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0284-z · Cited by 970 · see citing works
Thiele, E. A., Marsh, E. D., French, J. A., Mazurkiewicz-Beldzinska, M., Benbadis, S. R., Joshi, C., Lyons, P. D., Taylor, A., Roberts, C., Sommerville, K., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30136-3 · Cited by 905 · see citing works
The pharmacokinetics and the pharmacodynamics of cannabinoids
Lucas, C. J., Galettis, P., & Schneider, J. (2018) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13710 · Cited by 724 · see citing works
Practical considerations in medical cannabis administration and dosing
MacCallum, C. A., & Russo, E. B. (2018) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2018.01.004 · Cited by 663 · see citing works
Symonds, J. D., Zuberi, S. M., Stewart, K., McLellan, A., O‘Regan, M., MacLeod, S., Jollands, A., Joss, S., Kirkpatrick, M., Brunklaus, A., et al. (2019) · Brain · doi:10.1093/brain/awz195 · Cited by 459 · see citing works
Lagae, L., Sullivan, J., Knupp, K., Laux, L., Polster, T., Nikanorova, M., Devinsky, O., Cross, J. H., Guerrini, R., Talwar, D., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)32500-0 · Cited by 384 · see citing works
Self-citationIon Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies
Oyrer, J., Maljevic, S., Scheffer, I. E., Berkovic, S. F., Petrou, S., & Reid, C. A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014456 · Cited by 315 · see citing works
Self-citationTranslational investigation of the therapeutic potential of Cannabidiol (CBD): Toward a new age
Crippa, J. A., Guimarães, F. S., Campos, A. C., & Zuardi, A. W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02009 · Cited by 308 · see citing works
Thiele, E. A., Bebin, E. M., Bhathal, H., Jansen, F. E., Kotulska, K., Lawson, J. A., O'Callaghan, F. J., Wong, M., Sahebkar, F., Checketts, D., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2020.4607 · Cited by 281 · see citing works
Self-citationEarly childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants
Symonds, J. D., Elliott, K. S., Shetty, J., Armstrong, M., Brunklaus, A., Cutcutache, I., Diver, L. A., Dorris, L., Gardiner, S., Jollands, A., et al. (2021) · Brain · doi:10.1093/brain/awab162 · Cited by 269 · see citing works
Nabbout, R., Mistry, A., Zuberi, S., Villeneuve, N., Gil-Nagel, A., Sanchez-Carpintero, R., Stephani, U., Laux, L., Wirrell, E., Knupp, K., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.4113 · Cited by 251 · see citing works
Self-citationInternational consensus on diagnosis and management of Dravet syndrome
Wirrell, E. C., Hood, V., Knupp, K. G., Meskis, M. A., Nabbout, R., Scheffer, I. E., Wilmshurst, J., & Sullivan, J. (2022) · Epilepsia · doi:10.1111/epi.17274 · Cited by 249 · see citing works
Self-citationCannabinoid treatment for autism: a proof-of-concept randomized trial
Aran, A., Harel, M., Cassuto, H., Polyansky, L., Schnapp, A., Wattad, N., Shmueli, D., Golan, D., & Castellanos, F. X. (2021) · Molecular Autism · doi:10.1186/s13229-021-00420-2 · Cited by 223 · see citing works
Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum
Guerrini, R., Conti, V., Mantegazza, M., Balestrini, S., Galanopoulou, A. S., & Benfenati, F. (2023) · Physiological Reviews · doi:10.1152/physrev.00063.2021 · Cited by 196 · see citing works
Bilbao, A., & Spanagel, R. (2022) · BMC Medicine · doi:10.1186/s12916-022-02459-1 · Cited by 181 · see citing works
Beyond THC and Endocannabinoids
Pacher, P., Kogan, N. M., & Mechoulam, R. (2020) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010818-021441 · Cited by 175 · see citing works
Knight, E. M. P., Amin, S., Bahi-Buisson, N., Benke, T. A., Cross, J. H., Demarest, S. T., Olson, H. E., Specchio, N., Fleming, T. R., Aimetti, A. A., et al. (2022) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00077-1 · Cited by 160 · see citing works
Self-citationBurggren, A. C., Shirazi, A., Ginder, N., & London, E. D. (2019) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2019.1634086 · Cited by 144 · see citing works
Sholler, D. J., Schoene, L., & Spindle, T. R. (2020) · Current Addiction Reports · doi:10.1007/s40429-020-00326-8 · Cited by 143 · see citing works
Developmental and epileptic encephalopathies
Scheffer, I. E., Zuberi, S., Mefford, H. C., Guerrini, R., & McTague, A. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00546-6 · Cited by 128 · see citing works
Self-citationMonogenic Epilepsies: Disease Mechanisms, Clinical Phenotypes, and Targeted Therapies
Guerrini, R., Balestrini, S., Wirrell, E. C., & Walker, M. C. (2021) · Neurology · doi:10.1212/wnl.0000000000012744 · Cited by 108 · see citing works
Terpenoids From Cannabis Do Not Mediate an Entourage Effect by Acting at Cannabinoid Receptors
Finlay, D. B., Sircombe, K. J., Nimick, M., Jones, C., & Glass, M. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00359 · Cited by 99 · see citing works
“CBD is increasingly becoming a focus of therapeutic studies due to positive results in a series of childhood epilepsy clinical trials (Devinsky et al., 2017; Laux et al., 2019), yet its mechanism of action remains unclear, with over 65 putative molecular targets identified (Bih et al.”
Background“Is medical cannabis safe for my patients?” A practical review of cannabis safety considerations
MacCallum, C. A., Lo, L. A., & Boivin, M. (2021) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2021.05.002 · Cited by 71 · see citing works
Talwar, A., Estes, E., Aparasu, R., & Reddy, D. S. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114238 · Cited by 66 · see citing works
Specchio, N., Pietrafusa, N., Doccini, V., Trivisano, M., Darra, F., Ragona, F., Cossu, A., Spolverato, S., Battaglia, D., Quintiliani, M., et al. (2020) · Epilepsia · doi:10.1111/epi.16690 · Cited by 56 · see citing works
Palmer, E. E., Howell, K., & Scheffer, I. E. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01133-3 · Cited by 53 · see citing works
Self-citationde Aguiar, A. C., Vardanega, R., Viganó, J., & Silva, E. K. (2023) · Molecules · doi:10.3390/molecules28093849 · Cited by 51 · see citing works
Spanagel, R., & Bilbao, A. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108680 · Cited by 43 · see citing works
Makiello, P., Feng, T., Dunwoody, B., Steckler, F., Symonds, J., Zuberi, S. M., Dorris, L., & Brunklaus, A. (2023) · Epilepsia · doi:10.1111/epi.17531 · Cited by 26 · see citing works
A registry for Dravet syndrome: The Italian experience
Balestrini, S., Doccini, V., Giometto, S., Lucenteforte, E., De Masi, S., Giarola, E., Brambilla, I., Pieroni, F., Perulli, M., Battaglia, D., et al. (2023) · Epilepsia Open · doi:10.1002/epi4.12730 · Cited by 21 · see citing works
Chemaly, N., Kuchenbuch, M., Teng, T., Marie, E., D'Onofrio, G., Lo Barco, T., Brambilla, I., Flege, S., Hallet, A., & Nabbout, R. (2024) · Epilepsia Open · doi:10.1002/epi4.12557 · Cited by 20 · see citing works
Self-citationZakrzewski, D. M., Podlejska, P., Kubziakowska, W., Dzwilewski, K., Waszak, P. M., Zawadzka, M., & Mazurkiewicz-Bełdzińska, M. (2024) · Healthcare · doi:10.3390/healthcare12080830 · Cited by 3 · see citing works
- Authors
- Devinsky, O., Cross, J. H., Laux, L., Marsh, E., Miller, I., Nabbout, R., Scheffer, I. E., Thiele, E. A., & Wright, S.
- Affiliations
- Hôpital Necker-Enfants Malades (FR)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-05-25
- Volume
- 376
- Issue
- 21
- Pages
- 2011-2020
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2620218661
- Cited by
- 1,711
- References
- 11
- Citations by year
- 2026: 118 · 2025: 160 · 2024: 150 · 2023: 169 · 2022: 201 · 2021: 211 · 2020: 287 · 2019: 204 · 2018: 166 · 2017: 41 · 2016: 2
- FWCI
- 156.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- National Institute for Health and Care Research (NF-SI-0515-10073)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Keywords
- Dravet syndrome, cannabidiol, refractory seizures, pediatric epilepsy, anticonvulsant therapy, seizure reduction, adverse events, liver function tests, nonconvulsive seizures, seizure-free rate, trial withdrawal, fever, diarrhea, sleepiness, fatigue, antiepileptic drug resistance
- MeSH terms
- Adolescent, Anticonvulsants, Cannabidiol, Child, Child, Preschool, Double-Blind Method, Epilepsies, Myoclonic, Fatigue, Female, Humans, Liver, Liver Function Tests, Male, Seizures
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
